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Esper A. Cavalheiro - One of the best experts on this subject based on the ideXlab platform.

  • Hormonal and biochemical changes in female Proechimys guyannensis, an animal model of resistance to pilocarpine-induced status epilepticus
    Scientific Reports, 2020
    Co-Authors: Viviam Sanabria, Esper A. Cavalheiro, Simone Bittencourt, Sandra R. Perosa, Tomás De La Rosa, Maria Da Graça Naffah-mazzacoratti, Monica L. Andersen, Sergio Tufik, Débora Amado
    Abstract:

    AbstractThe Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though rarely getting sick. Previous studies on male Proechimys have revealed an endogenous resistance to epilepsy. Here, we assess in female Proechimys, whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX) Proechimys were compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE in Proechimys was higher (25- to 50-folds more). Despite a higher dose, Proechimys did not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that female Proechimys are resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance in Proechimys against SE induction.

  • Characterization of the estrous cycle in the Amazon spiny rat (Proechimys guyannensis).
    Heliyon, 2019
    Co-Authors: Viviam Sanabria, Carla A. Scorza, Esper A. Cavalheiro, Simone Bittencourt, Tomás De La Rosa, Jomênica De Bortoli Livramento, Célia Harumi Tengan, Débora Amado
    Abstract:

    Abstract Males of Proechimys guyannensis, a rodent living in the Amazon rainforest are studied in biomedical research because of their antiepileptogenic mechanism. Females are usually taken from experimental designs, because of limited data of this sex. This study aimed to characterize the estrous cycle to include females together with males in research in a more balanced approach. The estrous cycle of P. guyannensis based through exfoliative cytology, determination of the vaginal occlusion membrane state, and hormonal analysis. In this study, cytological analyses of vaginal smears were performed for three months, three times a day. The observed length of the estrous cycle was 247 ± 81 h (mean ± SD) with a reproductive phase of 27.08 ± 17.39 h (estrus stage). We observed a frequent presence of both the open and closed states of the vaginal membrane in the estrus stage (fertile period) although only the open stage is a prerequisite for successful copulation. High levels of progesterone and estradiol were detected in proestrus. Levels of follicle-stimulating hormone peaked at the estrus stage. These data will establish the parameters and subsidies to set the grounds for future research either for investigating the biology of this species or to use P. guyannensis in research that previously excluded females. Information regarding female Proechimys is relevant to not only describe the species but also explain the interaction between sex hormones and physiological responses. Moreover, the present results will enhance rigor and reproducibility in preclinical studies. In conclusion, P. guyannensis reproductive cycles can occur spontaneously and cyclically independent of mating stimulation and the high levels of FSH in the estrus stage, suggest that ovulation occurs in the late phase of the estrus.

  • Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys.
    Neuroscience letters, 2019
    Co-Authors: Marcia J.g. Marques, Fulvio A. Scorza, Esper A. Cavalheiro, Caroline C. Real, Daniella Balduino Victorino, Luiz R.g. Britto, Henrique Ballalai Ferraz, Carla A. Scorza
    Abstract:

    Abstract Background Proechimys, an epilepsy-resistant rodent from Amazon Rainforest, is a promising alternative animal model for studying neurodegenerative disorders. Objectives To evaluate behavioral and immunohistological changes in Proechimys after 6−OHDA-induced model of PD. Methods Following unilateral injections of 6−OHDA into striatum, animals were assessed for exploratory behavior using the cylinder test. Brain sections were submitted to immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1). Results We observed normal exploratory behavior during cylinder test in all animals. We could not detect changes in the expression of TH in both striatum and SNc, suggesting that Proechimys is resistant to dopaminergic neuronal degeneration. Glial activation was observed by an increase in Iba-1 expression in both striatum and SNc, and by an increase in GFAP expression in striatum. Conclusions Proechimys represents a promising animal model for studying the mechanisms underlying the susceptibility of dopaminergic neurons to degeneration induced by 6−OHDA.

  • Robust Network Inhibition and Decay of Early-Phase LTP in the Hippocampal CA1 Subfield of the Amazon Rodent Proechimys.
    Frontiers in neural circuits, 2018
    Co-Authors: Selvin Z. Reyes-garcia, Fulvio A. Scorza, Esper A. Cavalheiro, Antonio-carlos G. De Almeida, Nancy N. Ortiz-villatoro, Carla A. Scorza
    Abstract:

    Background: Diverse forms of long-term potentiation (LTP) have been described, but one of the most investigated is encountered in the glutamatergic synapses of the hippocampal cornu Ammonis (CA1) subfield. However, little is known about synaptic plasticity in wildlife populations. Laboratory animals are extremely inbred populations that have been disconnected from their natural environment and so their essential ecological aspects are entirely absent. Proechimys are small rodents from Brazil's Amazon rainforest and their nervous systems have evolved to carry out specific tasks of their unique ecological environment. It has also been shown that long-term memory duration did not persist for 24-h in Proechimys, in contrast to Wistar rats, when both animal species were assessed by the plus-maze discrimination avoidance task and object recognition test. Methods: In this work, different protocols, such as theta burst, single tetanic burst or multiple trains of high frequency stimulation (HFS), were used to induce LTP in hippocampal brain slices of Proechimys and Wistar rats. Results: A protocol-independent fast decay of early-phase LTP at glutamatergic synapses of the CA1 subfield was encountered in Proechimys. Long-term depression (LTD) and baseline paired-pulse facilitation (PPF) were investigated but no differences were found between animal species. Input/output (I/O) relationships suggested lower excitability in Proechimys in comparison to Wistar rats. Bath application of d-(-)-2-amino-5-phosphonopentanoicacid (D-AP5) and CNQX prevented the induction of LTP in both Proechimys and Wistar. However, in marked contrast to Wistar rats, LTP induction was not facilitated by the GABAA antagonist in the Amazon rodents, even higher concentrations failed to facilitate LTP in Proechimys. Next, the effects of GABAA inhibition on spontaneous activity as well as evoked field potentials (FPs) were evaluated in CA1 pyramidal cells. Likewise, much lower activity was detected in Proechimys brain slices in comparison to those of the Wistar rats. Conclusions: These findings suggest a possible high inhibitory tone in the CA1 network mediated by GABAA receptors in the Amazon rodents. Currently, neuroscience research still seeks to reveal molecular pathways that control learning and memory processes, Proechimys may prove useful in identifying such mechanisms in complement to traditional animal models.

  • Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest
    Frontiers in behavioral neuroscience, 2018
    Co-Authors: Marcia J.g. Marques, Fulvio A. Scorza, Esper A. Cavalheiro, Monica L. Andersen, Selvin Z. Reyes-garcia, José Eduardo Marques-carneiro, L.b. Lopes-silva, Carla A. Scorza
    Abstract:

    Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

Carla A. Scorza - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of the estrous cycle in the Amazon spiny rat (Proechimys guyannensis).
    Heliyon, 2019
    Co-Authors: Viviam Sanabria, Carla A. Scorza, Esper A. Cavalheiro, Simone Bittencourt, Tomás De La Rosa, Jomênica De Bortoli Livramento, Célia Harumi Tengan, Débora Amado
    Abstract:

    Abstract Males of Proechimys guyannensis, a rodent living in the Amazon rainforest are studied in biomedical research because of their antiepileptogenic mechanism. Females are usually taken from experimental designs, because of limited data of this sex. This study aimed to characterize the estrous cycle to include females together with males in research in a more balanced approach. The estrous cycle of P. guyannensis based through exfoliative cytology, determination of the vaginal occlusion membrane state, and hormonal analysis. In this study, cytological analyses of vaginal smears were performed for three months, three times a day. The observed length of the estrous cycle was 247 ± 81 h (mean ± SD) with a reproductive phase of 27.08 ± 17.39 h (estrus stage). We observed a frequent presence of both the open and closed states of the vaginal membrane in the estrus stage (fertile period) although only the open stage is a prerequisite for successful copulation. High levels of progesterone and estradiol were detected in proestrus. Levels of follicle-stimulating hormone peaked at the estrus stage. These data will establish the parameters and subsidies to set the grounds for future research either for investigating the biology of this species or to use P. guyannensis in research that previously excluded females. Information regarding female Proechimys is relevant to not only describe the species but also explain the interaction between sex hormones and physiological responses. Moreover, the present results will enhance rigor and reproducibility in preclinical studies. In conclusion, P. guyannensis reproductive cycles can occur spontaneously and cyclically independent of mating stimulation and the high levels of FSH in the estrus stage, suggest that ovulation occurs in the late phase of the estrus.

  • Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys.
    Neuroscience letters, 2019
    Co-Authors: Marcia J.g. Marques, Fulvio A. Scorza, Esper A. Cavalheiro, Caroline C. Real, Daniella Balduino Victorino, Luiz R.g. Britto, Henrique Ballalai Ferraz, Carla A. Scorza
    Abstract:

    Abstract Background Proechimys, an epilepsy-resistant rodent from Amazon Rainforest, is a promising alternative animal model for studying neurodegenerative disorders. Objectives To evaluate behavioral and immunohistological changes in Proechimys after 6−OHDA-induced model of PD. Methods Following unilateral injections of 6−OHDA into striatum, animals were assessed for exploratory behavior using the cylinder test. Brain sections were submitted to immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1). Results We observed normal exploratory behavior during cylinder test in all animals. We could not detect changes in the expression of TH in both striatum and SNc, suggesting that Proechimys is resistant to dopaminergic neuronal degeneration. Glial activation was observed by an increase in Iba-1 expression in both striatum and SNc, and by an increase in GFAP expression in striatum. Conclusions Proechimys represents a promising animal model for studying the mechanisms underlying the susceptibility of dopaminergic neurons to degeneration induced by 6−OHDA.

  • Robust Network Inhibition and Decay of Early-Phase LTP in the Hippocampal CA1 Subfield of the Amazon Rodent Proechimys.
    Frontiers in neural circuits, 2018
    Co-Authors: Selvin Z. Reyes-garcia, Fulvio A. Scorza, Esper A. Cavalheiro, Antonio-carlos G. De Almeida, Nancy N. Ortiz-villatoro, Carla A. Scorza
    Abstract:

    Background: Diverse forms of long-term potentiation (LTP) have been described, but one of the most investigated is encountered in the glutamatergic synapses of the hippocampal cornu Ammonis (CA1) subfield. However, little is known about synaptic plasticity in wildlife populations. Laboratory animals are extremely inbred populations that have been disconnected from their natural environment and so their essential ecological aspects are entirely absent. Proechimys are small rodents from Brazil's Amazon rainforest and their nervous systems have evolved to carry out specific tasks of their unique ecological environment. It has also been shown that long-term memory duration did not persist for 24-h in Proechimys, in contrast to Wistar rats, when both animal species were assessed by the plus-maze discrimination avoidance task and object recognition test. Methods: In this work, different protocols, such as theta burst, single tetanic burst or multiple trains of high frequency stimulation (HFS), were used to induce LTP in hippocampal brain slices of Proechimys and Wistar rats. Results: A protocol-independent fast decay of early-phase LTP at glutamatergic synapses of the CA1 subfield was encountered in Proechimys. Long-term depression (LTD) and baseline paired-pulse facilitation (PPF) were investigated but no differences were found between animal species. Input/output (I/O) relationships suggested lower excitability in Proechimys in comparison to Wistar rats. Bath application of d-(-)-2-amino-5-phosphonopentanoicacid (D-AP5) and CNQX prevented the induction of LTP in both Proechimys and Wistar. However, in marked contrast to Wistar rats, LTP induction was not facilitated by the GABAA antagonist in the Amazon rodents, even higher concentrations failed to facilitate LTP in Proechimys. Next, the effects of GABAA inhibition on spontaneous activity as well as evoked field potentials (FPs) were evaluated in CA1 pyramidal cells. Likewise, much lower activity was detected in Proechimys brain slices in comparison to those of the Wistar rats. Conclusions: These findings suggest a possible high inhibitory tone in the CA1 network mediated by GABAA receptors in the Amazon rodents. Currently, neuroscience research still seeks to reveal molecular pathways that control learning and memory processes, Proechimys may prove useful in identifying such mechanisms in complement to traditional animal models.

  • Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest
    Frontiers in behavioral neuroscience, 2018
    Co-Authors: Marcia J.g. Marques, Fulvio A. Scorza, Esper A. Cavalheiro, Monica L. Andersen, Selvin Z. Reyes-garcia, José Eduardo Marques-carneiro, L.b. Lopes-silva, Carla A. Scorza
    Abstract:

    Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

  • Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.
    Neuroscience letters, 2017
    Co-Authors: Carla A. Scorza, Fulvio A. Scorza, Maria Da Graça Naffah-mazzacoratti, Marcia J.g. Marques, Sérgio Gomes Da Silva, Esper A. Cavalheiro
    Abstract:

    Abstract Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1 β , IL-6, IL-10, TNF-α) and VEGF remained unchanged 24 h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys .

Marina Bentivoglio - One of the best experts on this subject based on the ideXlab platform.

  • different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy resistant Proechimys rats versus wistar rats after pilocarpine induced protracted seizures
    Epilepsia, 2009
    Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina Bentivoglio
    Abstract:

    Summary Purpose:  To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods:  Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results:  In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion:  At variance with laboratory rats, pilocarpine-induced protracted seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in limbic seizure suppression leading to epilepsy resistance.

  • Different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy-resistant Proechimys rats versus Wistar rats after pilocarpine-induced protracted seizures.
    Epilepsia, 2009
    Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina Bentivoglio
    Abstract:

    Summary Purpose:  To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods:  Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results:  In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when

  • Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures.
    Hippocampus, 2004
    Co-Authors: Paolo F. Fabene, Esper A. Cavalheiro, Anna Andrioli, Margareth Rose Priel, Marina Bentivoglio
    Abstract:

    Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.

  • The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.
    Neuroscience, 2001
    Co-Authors: Paolo F. Fabene, Esper A. Cavalheiro, Luciana Correia, R.a Carvalho, Marina Bentivoglio
    Abstract:

    Abstract At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase 67 -immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

Paolo F. Fabene - One of the best experts on this subject based on the ideXlab platform.

  • different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy resistant Proechimys rats versus wistar rats after pilocarpine induced protracted seizures
    Epilepsia, 2009
    Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina Bentivoglio
    Abstract:

    Summary Purpose:  To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods:  Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results:  In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion:  At variance with laboratory rats, pilocarpine-induced protracted seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in limbic seizure suppression leading to epilepsy resistance.

  • Different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy-resistant Proechimys rats versus Wistar rats after pilocarpine-induced protracted seizures.
    Epilepsia, 2009
    Co-Authors: Anna Andrioli, Esper A. Cavalheiro, Paolo F. Fabene, Roberto Spreafico, Marina Bentivoglio
    Abstract:

    Summary Purpose:  To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods:  Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of γ-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results:  In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10–20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when

  • Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures.
    Hippocampus, 2004
    Co-Authors: Paolo F. Fabene, Esper A. Cavalheiro, Anna Andrioli, Margareth Rose Priel, Marina Bentivoglio
    Abstract:

    Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.

  • The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.
    Neuroscience, 2001
    Co-Authors: Paolo F. Fabene, Esper A. Cavalheiro, Luciana Correia, R.a Carvalho, Marina Bentivoglio
    Abstract:

    Abstract At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase 67 -immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

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  • Hormonal and biochemical changes in female Proechimys guyannensis, an animal model of resistance to pilocarpine-induced status epilepticus
    Scientific Reports, 2020
    Co-Authors: Viviam Sanabria, Esper A. Cavalheiro, Simone Bittencourt, Sandra R. Perosa, Tomás De La Rosa, Maria Da Graça Naffah-mazzacoratti, Monica L. Andersen, Sergio Tufik, Débora Amado
    Abstract:

    AbstractThe Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though rarely getting sick. Previous studies on male Proechimys have revealed an endogenous resistance to epilepsy. Here, we assess in female Proechimys, whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX) Proechimys were compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE in Proechimys was higher (25- to 50-folds more). Despite a higher dose, Proechimys did not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that female Proechimys are resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance in Proechimys against SE induction.

  • Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest
    Frontiers in behavioral neuroscience, 2018
    Co-Authors: Marcia J.g. Marques, Fulvio A. Scorza, Esper A. Cavalheiro, Monica L. Andersen, Selvin Z. Reyes-garcia, José Eduardo Marques-carneiro, L.b. Lopes-silva, Carla A. Scorza
    Abstract:

    Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

  • Characterization of the sleep–wake cycle of the Neotropical rodent Proechimys guyannensis
    SAGE open medicine, 2014
    Co-Authors: Jose C. Da Silva, Monica L. Andersen, Sergio Tufik, Gabriela De Matos Barbosa Pimenta, Gerhardus Hermanus Maria Schoorlemmer, Esper A. Cavalheiro
    Abstract:

    OBJECTIVES To better understand the sleep-wake cycle characteristics in the female Neotropical rodent Proechimys guyannensis related to comparative neurobiology. METHODS Surface neocortical and hippocampal electrodes were chronically implanted in the brains of female Wistar and Proechimys animals. In addition, electrodes for the study of muscle activity were implanted into the neck muscle of both species. After surgical recovery and a period of adaptation, animals were continuously registered for periods as long as 48 h. RESULTS In both the light and dark phases of the cycle, significant differences in some electrographic patterns were observed between the Proechimys and Wistar animals. Although Proechimys has nocturnal activities and a pattern of polyphasic sleep similar to Wistar rats, the analysis of its sleep-wakefulness cycle indicates that the Neotropical rodent sleeps less with consequent longer periods of wakefulness when compared to Wistar rats. CONCLUSIONS Together with previous findings of different neuroanatomical, neurophysiologic and behavioral characteristics, this study allow us to better understand adaptive differences of the Neotropical rodent Proechimys.

  • characterization of the sleep wake cycle of the neotropical rodent Proechimys guyannensis
    Sage Open Medicine, 2014
    Co-Authors: Jose C. Da Silva, Monica L. Andersen, Sergio Tufik, Gabriela De Matos Barbosa Pimenta, Gerhardus Hermanus Maria Schoorlemmer, Esper A. Cavalheiro
    Abstract:

    OBJECTIVES To better understand the sleep-wake cycle characteristics in the female Neotropical rodent Proechimys guyannensis related to comparative neurobiology. METHODS Surface neocortical and hippocampal electrodes were chronically implanted in the brains of female Wistar and Proechimys animals. In addition, electrodes for the study of muscle activity were implanted into the neck muscle of both species. After surgical recovery and a period of adaptation, animals were continuously registered for periods as long as 48 h. RESULTS In both the light and dark phases of the cycle, significant differences in some electrographic patterns were observed between the Proechimys and Wistar animals. Although Proechimys has nocturnal activities and a pattern of polyphasic sleep similar to Wistar rats, the analysis of its sleep-wakefulness cycle indicates that the Neotropical rodent sleeps less with consequent longer periods of wakefulness when compared to Wistar rats. CONCLUSIONS Together with previous findings of different neuroanatomical, neurophysiologic and behavioral characteristics, this study allow us to better understand adaptive differences of the Neotropical rodent Proechimys.

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