The Experts below are selected from a list of 363 Experts worldwide ranked by ideXlab platform
F.w. Van Leeuwen - One of the best experts on this subject based on the ideXlab platform.
-
Lack of translation of normal 7B2 mRNA levels in hypothalamic mutant vasopressin cells of the homozygous BRattleboro Rat
Neuroscience letters, 1997Co-Authors: B. A. Th. F. Gabreëls, A.a. Sluiter, R.w.h. Verwer, M. A. F. Sonnemans, C.w Ang, F.w. Van LeeuwenAbstract:The homozygous BRattleboro Rat (di/di) synthesizes a vasopressin (VP) precursor with an aberrant C-terminus, which causes a hypothalamic form of diabetes insipidus. The neuroendocrine polypeptide 7B2 is present in VP and oxytocin (OT) neurons of the supraoptic and paraventricular nucleus of the hypothalamus in wild type Rats. However, in the di/di Rat 7B2 immunoreactivity is absent in the VP cell population, whereas 7B2 levels within the OT cells are unaffected. Remarkably, there is no obvious difference in 7B2 transcript levels between VP and OT neurons in the di/di Rat hypothalamus. This study shows that the presence of mRNA does not automatically result in the subsequent synthesis of its protein. Cellular mechanisms underlying this discrepancy are discussed.
-
Immunocytochemical evidence for the presence of vasopressin in intermediate sized neurosecretory granules of solitary neurohypophyseal terminals in the homozygous BRattleboro Rat
Neuroscience, 1996Co-Authors: J.p.h. Burbach, M. A. F. Sonnemans, D A Evans, F.w. Van LeeuwenAbstract:Abstract A single base deletion (ΔG) in the vasopressin gene is the cause of diabetes insipidus in the homozygous BRattleboro Rat (di/di). The resulting frameshift leads to the expression of an aberrant vasopressin precursor which is unable to enter the secretory pathway, thereby preventing vasopressin biosynthesis. In a small number of solitary magnocellular hypothalamic neurons within the supraoptic and paraventricular nuclei, the reading frame is restored by a dinucleotide (ΔGA) frameshift mutation, at two sepaRate GAGAG motifs downstream of the original G-deletion. This results in two + 1 di-vasopressin precursors that are still partially mutated within the neurophysin region. The present study provides immunocytochemical evidence which demonstRates that, within magnocellular solitary neurons of the supraoptic and paraventricular nuclei of the di/di Rat, the + 1 di-vasopressin precursors can enter the secretory pathway followed by their enzymatic processing into vasopressin during axonal transport to the neural lobe. However, the cellular characteristics of biosynthesis are different from those of wild-type Rats. Immunoelectron microscopical localization of vasopressin gene products in the neural lobe of di/di Rats revealed their presence in neurosecretory granules, the diameter of which is intermediate (116 nm) between those of the neurosecretory granules in the di/di (80–100 nm) and wild-type (160 nm) Rats.
-
Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: J.p.h. Burbach, M. A. F. Sonnemans, D A Evans, A. A. M. Van Der Kleij, F.w. Van LeeuwenAbstract:Abstract Mutations in DNA underlie carcinogenesis, inherited pathology, and aging and are generally thought to be introduced during meiosis and mitosis. Here we report that in post-mitotic neurons specific frameshift mutations occur at high frequency. These mutations were identified in vasopressin transcripts in magnocellular neurons of the homozygous BRattleboro Rat and predominantly consist of a GA deletion in GAGAG motifs. Immunocytochemistry provides evidence for similar events in wild-type Rats. However, the diseased state of the BRattleboro Rat, resulting in a permanent activation of vasopressin neurons, enhanced the mutational Rate. These data reveal hitherto unrecognized somatic mutations in nondividing neurons.
-
Differential neurophysin immunoreactivities in solitary magnocellular neurons of the homozygous BRattleboro Rat indicate an altered neurophysin moiety.
Brain research, 1994Co-Authors: F.w. Van Leeuwen, M. A. F. Sonnemans, D A Evans, R MeloenAbstract:In the homozygous BRattleboro Rat (di/di) a single base deletion in the vasopressin (VP) gene causes diabetes insipidus, resulting in the synthesis of a VP precursor with a different C-terminus. We reported previously that a small number of post-mitotic VP neurons in di/di Rats undergo a switch to a heterozygous phenotype, suggesting the existence of VP mRNAs with a restored reading frame coding for a normal VP precursor. In the present study we report that the increase in the number of these revertant cells declines after 79 weeks of age. Furthermore, we provide evidence that the neurophysin (NP) moiety in solitary neurons is different from normal NP. Comparing the immunoreactivities of two different NP antibodies we deduced that the restoRation of the reading frame may take place downstream of the deletion between amino acids 75 and 93 of the VP-NP.
-
Dynamics of 7B2 and galanin expression in solitary magnocellular hypothalamic vasopressin neurons of the homozygous BRattleboro Rat.
Brain research, 1992Co-Authors: B. A. Th. F. Gabreëls, M. Chretien, N.g. Seidah, M. A. F. Sonnemans, F.w. Van LeeuwenAbstract:The homozygous BRattleboro Rat (di/di), displaying a hypothalamic form of diabetes insipidus, synthesizes a vasopressin (VP) precursor with an abnormal C-terminus. The phenotypic expression of coexisting peptides in mutant magnocellular VP cells shows a differential pattern. 7B2 is one of the peptides which is not detectable, whereas there is a clear galanin expression. During postnatal life a small but increasing number of solitary post-mitotic VP neurons of the di/di Rat undergoes a switch to a heterozygous phenotype. Here we report the presence of 7B2 and galanin in these heterozygous cells, which suggests that for the expression of 7B2, but not for that of galanin, the relative amount of mutant VP precursor must be diminished. Possible underlying mechanisms for this differential phenotypic expression of coexisting peptides are compartmentalization of precursor synthesis within the RER or a competition for sites involved in the translocation of the functionally reduced RER.
Dóra Zelena - One of the best experts on this subject based on the ideXlab platform.
-
amelioRating schizophrenia like symptoms in vasopressin deficient male BRattleboro Rat by chronic antipsychotic treatment
European Journal of Pharmacology, 2021Co-Authors: Bibiana Torok, Barbara Klausz, Anna Fodor, Janos Tamas Varga, Dóra ZelenaAbstract:Abstract Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) BRattleboro Rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment effects of marketed antipsychotics are similar in di/di Rats to those seen in human schizophrenic patients. Chronic subcutaneous administRation of aripiprazole (5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.3 mg/kg) or risperidone (0.25 mg/kg) was used for 15 days in control (+/+ BRattleboro) and di/di Rats. Social discrimination, social avoidance and prepulse inhibition tests were conducted on day 1, 8 and 15 of the treatment. Vasopressin-deficient Rats showed social memory- and sensorimotor gating deficit. All used antipsychotics successfully normalized the reduced prepulse inhibition of di/di animals. However, most were effective only after prolonged treatment. Aripiprazole, clozapine, and olanzapine normalized the social memory deficit, while the effects of haloperidol and risperidone were not unequivocal. All drugs reduced social interest to some extent both in control and in di/di animals, aripiprazole being the less implicated in this regard during the social avoidance test. The restoRation of schizophrenia-like behavior by antipsychotic treatment further support the utility of the vasopressin-deficient BRattleboro Rat as a good preclinical model. Reduced social interest might be a general side-effect of antipsychotics, and aripiprazole has the most favorable profile in this regard.
-
The prepulse inhibition deficit appearance is largely independent on the circadian cycle, body weight, and the gender of vasopressin deficient BRattleboro Rat.
Endocrine regulations, 2016Co-Authors: Barbara Klausz, Anna Fodor, Blanka Tóth, Dóra ZelenaAbstract:OBJECTIVE A disturbance of sensorimotor gating measured by prepulse inhibition of acoustic startle (PPI) is one of the best tests of the schizophrenia-like behavior. Vasopressin was implicated in the development of schizophrenia; therefore, the naturally occurring vasopressin-deficient BRattleboro Rat has been suggested to be a reliable non-pharmacological animal model. However, previous studies focusing on PPI deficit did not use proper control and despite clear gender differences in the development of the disorder, the effect of gender has been mostly neglected. METHODS First, we compared the "noise" and "tone" type prepulse at 73-77-81 dB intensity during the light or dark phase using small (~150 g) or big (~500 g) Wistar Rats. The test parameters were validated by a pharmacological schizophrenia model (30 mg/kg ketamine i.p.). Than male, female, and lactating vasopressin-deficient animals were compared with +/+ ones. RESULTS We established that the prepulse "noise" type is not optimal for PPI testing. The cycle of the day as well as the body weight had no effect on PPI. Even if we compared vasopressin-deficient animals with their closely related +/+ controls, the PPI deficiency was visible with more pronounced effect at 77 dB prepulse intensity similarly to pharmacological schizophrenia model. Despite our expectation, the gender as well as lactation had no effect on the vasopressin-deficiency induced PPI deficit. CONCLUSIONS The present data confirmed and extended our previous studies that vasopressin-deficient Rat is a good model of schizophrenia. It seems that female as well as lactating BRattleboro Rats are useful tools for testing putative novel antipsychotics in line with special attention required for schizophrenic women.
-
Vasopressin signaling at brain level controls stress hormone release: the vasopressin-deficient BRattleboro Rat as a model
Amino Acids, 2015Co-Authors: Dóra Zelena, Ottó Pintér, Diána Gabriella Balázsfi, Kristina Langnaese, Karin Richter, Rainer Landgraf, Gábor B. Makara, Mario EngelmannAbstract:The nonapeptide arginine vasopressin (AVP) has long been suggested to play an important role as a secretagogue for triggering the activity of the endocrine stress response. Most recent studies employed mutant mice for analyzing the importance of AVP for endocrine regulation under stress. However, it is difficult to compare and draw overall conclusions from all these studies as mixing the genetic material from different mouse strains has consequences on the individual’s stress response. Moreover, mice are not ideal subjects for several experimental procedures. Therefore, to get more insight, we used a Rather old mutant Rat model: the AVP-deficient BRattleboro Rat. The present short review is aimed at providing the most interesting results of these studies within the last 8 years that allowed gaining new insights in the potential signal function of AVP in stress and endocrine regulation.
-
the vasopressin deficient BRattleboro Rat lessons for the hypothalamo pituitary adrenal axis regulation
Cellular and Molecular Neurobiology, 2012Co-Authors: G B Makara, Ottó Pintér, István Barna, Barbara Klausz, Janos Varga, Dóra ZelenaAbstract:Adaptation to stress is indispensable to life and the hypothalamo–pituitary–adrenocortical axis is one of the major components of the adaptation. The hypothalamic component consists of corticotropin-releasing hormone and arginine vasopressin, with a questionable contribution of the latter. Vasopressin was more important in the regulation of the adrenocorticotropin secretion in the perinatal vasopressin-deficient BRattleboro Rats than in adulthood, where its role depended on the nature of the stressor encountered. In adults, the vasopressin deficiency did not influence the development of chronic stress response. In the neonatal Rats, the role of vasopressin was supported by the inhibitory action of a V1b antagonist and vasopressin antiserum. As the corticosterone response to stress did not follow the adrenocorticotropin levels, we assume the presence of an adrenocorticotropin independent adrenal gland regulation in the neonates. We have shown that the apparent dissociation of the corticosterone and adrenocorticotropin responses is not due to the different time course of the two hormone responses, to different level of the corticosterone binding globulin or to changes in the adrenal gland sensitivity. In vitro experiments point to the contribution of beta-adrenoceptors in the process. It was also confirmed by in vivo tests using the vasopressin-deficient BRattleboro pup as a model organism, where corticosterone levels may rise without adrenocorticotropin level changes. Another important question is the role of adrenocorticotropin beyond the corticosterone secretion regulation, which could be supposed, e.g., in cardiovascular events, immunological processes, and metabolism. We can conclude that BRattleboro Rats gave us much information about the stress-axis regulation far beyond the role of vasopressin itself.
-
acute ether stress differentially affects corticotropin releasing factor and urocortin 1 in the BRattleboro Rat
Brain Research, 2011Co-Authors: Linda Sterrenburg, Dóra Zelena, Ottó Pintér, Alexandra Borch, B W M M Peeters, Eric W Roubos, Tamas KoziczAbstract:Arginine-vasopressin (AVP), corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) play a role in the stress response. The CRF-producing paraventricular nucleus of the hypothalamus (PVN), oval bed nucleus of the stria terminalis (BSTov) and central amygdala (CeA), and the Ucn1-expressing non-preganglionic Edinger-Westphal nucleus (npEW) all possess AVP receptors. We hypothesized that AVP is involved in the response of these four brain centers to acute physiological (ether) stress. To test this hypothesis, we studied AVP-deficient BRattleboro (BB) Rats using quantitative immunocytochemistry. First, we showed that non-stressed wild-type (WT) and BB Rats did not differ from each other in Fos contents, indicating similar (immediate early) gene expression activity, but that in BB Rats CRF contents were lower in the PVN and higher in the CeA. Second, we found that stress induced Fos response in the PVN, CeA and npEW with strengths different for each center, but similar for BB and WT Rats. Finally, no effects of stress on CRF and Ucn1 contents were seen in the WT Rat brain, but in BB Rats stress increased CRF contents in the PVN, and the CeA revealed more CRF in stressed BB than in WT Rats. On the basis of these results we propose that during acute stress AVP interacts with, especially, the PVN and the CeA, to change their Rates of biosynthesis and/or release of CRF.
M. A. F. Sonnemans - One of the best experts on this subject based on the ideXlab platform.
-
Lack of translation of normal 7B2 mRNA levels in hypothalamic mutant vasopressin cells of the homozygous BRattleboro Rat
Neuroscience letters, 1997Co-Authors: B. A. Th. F. Gabreëls, A.a. Sluiter, R.w.h. Verwer, M. A. F. Sonnemans, C.w Ang, F.w. Van LeeuwenAbstract:The homozygous BRattleboro Rat (di/di) synthesizes a vasopressin (VP) precursor with an aberrant C-terminus, which causes a hypothalamic form of diabetes insipidus. The neuroendocrine polypeptide 7B2 is present in VP and oxytocin (OT) neurons of the supraoptic and paraventricular nucleus of the hypothalamus in wild type Rats. However, in the di/di Rat 7B2 immunoreactivity is absent in the VP cell population, whereas 7B2 levels within the OT cells are unaffected. Remarkably, there is no obvious difference in 7B2 transcript levels between VP and OT neurons in the di/di Rat hypothalamus. This study shows that the presence of mRNA does not automatically result in the subsequent synthesis of its protein. Cellular mechanisms underlying this discrepancy are discussed.
-
Immunocytochemical evidence for the presence of vasopressin in intermediate sized neurosecretory granules of solitary neurohypophyseal terminals in the homozygous BRattleboro Rat
Neuroscience, 1996Co-Authors: J.p.h. Burbach, M. A. F. Sonnemans, D A Evans, F.w. Van LeeuwenAbstract:Abstract A single base deletion (ΔG) in the vasopressin gene is the cause of diabetes insipidus in the homozygous BRattleboro Rat (di/di). The resulting frameshift leads to the expression of an aberrant vasopressin precursor which is unable to enter the secretory pathway, thereby preventing vasopressin biosynthesis. In a small number of solitary magnocellular hypothalamic neurons within the supraoptic and paraventricular nuclei, the reading frame is restored by a dinucleotide (ΔGA) frameshift mutation, at two sepaRate GAGAG motifs downstream of the original G-deletion. This results in two + 1 di-vasopressin precursors that are still partially mutated within the neurophysin region. The present study provides immunocytochemical evidence which demonstRates that, within magnocellular solitary neurons of the supraoptic and paraventricular nuclei of the di/di Rat, the + 1 di-vasopressin precursors can enter the secretory pathway followed by their enzymatic processing into vasopressin during axonal transport to the neural lobe. However, the cellular characteristics of biosynthesis are different from those of wild-type Rats. Immunoelectron microscopical localization of vasopressin gene products in the neural lobe of di/di Rats revealed their presence in neurosecretory granules, the diameter of which is intermediate (116 nm) between those of the neurosecretory granules in the di/di (80–100 nm) and wild-type (160 nm) Rats.
-
Frameshift mutations at two hotspots in vasopressin transcripts in post-mitotic neurons.
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: J.p.h. Burbach, M. A. F. Sonnemans, D A Evans, A. A. M. Van Der Kleij, F.w. Van LeeuwenAbstract:Abstract Mutations in DNA underlie carcinogenesis, inherited pathology, and aging and are generally thought to be introduced during meiosis and mitosis. Here we report that in post-mitotic neurons specific frameshift mutations occur at high frequency. These mutations were identified in vasopressin transcripts in magnocellular neurons of the homozygous BRattleboro Rat and predominantly consist of a GA deletion in GAGAG motifs. Immunocytochemistry provides evidence for similar events in wild-type Rats. However, the diseased state of the BRattleboro Rat, resulting in a permanent activation of vasopressin neurons, enhanced the mutational Rate. These data reveal hitherto unrecognized somatic mutations in nondividing neurons.
-
Differential neurophysin immunoreactivities in solitary magnocellular neurons of the homozygous BRattleboro Rat indicate an altered neurophysin moiety.
Brain research, 1994Co-Authors: F.w. Van Leeuwen, M. A. F. Sonnemans, D A Evans, R MeloenAbstract:In the homozygous BRattleboro Rat (di/di) a single base deletion in the vasopressin (VP) gene causes diabetes insipidus, resulting in the synthesis of a VP precursor with a different C-terminus. We reported previously that a small number of post-mitotic VP neurons in di/di Rats undergo a switch to a heterozygous phenotype, suggesting the existence of VP mRNAs with a restored reading frame coding for a normal VP precursor. In the present study we report that the increase in the number of these revertant cells declines after 79 weeks of age. Furthermore, we provide evidence that the neurophysin (NP) moiety in solitary neurons is different from normal NP. Comparing the immunoreactivities of two different NP antibodies we deduced that the restoRation of the reading frame may take place downstream of the deletion between amino acids 75 and 93 of the VP-NP.
-
Dynamics of 7B2 and galanin expression in solitary magnocellular hypothalamic vasopressin neurons of the homozygous BRattleboro Rat.
Brain research, 1992Co-Authors: B. A. Th. F. Gabreëls, M. Chretien, N.g. Seidah, M. A. F. Sonnemans, F.w. Van LeeuwenAbstract:The homozygous BRattleboro Rat (di/di), displaying a hypothalamic form of diabetes insipidus, synthesizes a vasopressin (VP) precursor with an abnormal C-terminus. The phenotypic expression of coexisting peptides in mutant magnocellular VP cells shows a differential pattern. 7B2 is one of the peptides which is not detectable, whereas there is a clear galanin expression. During postnatal life a small but increasing number of solitary post-mitotic VP neurons of the di/di Rat undergoes a switch to a heterozygous phenotype. Here we report the presence of 7B2 and galanin in these heterozygous cells, which suggests that for the expression of 7B2, but not for that of galanin, the relative amount of mutant VP precursor must be diminished. Possible underlying mechanisms for this differential phenotypic expression of coexisting peptides are compartmentalization of precursor synthesis within the RER or a competition for sites involved in the translocation of the functionally reduced RER.
P. Te Riele - One of the best experts on this subject based on the ideXlab platform.
-
Early postnatal appearance of enhanced noradrenaline content in the brain of vasopressin-deficient BRattleboro Rat; normal adrenoceptor densities and aberrant influences of vasopressin treatment
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 1995Co-Authors: Gerard J. Boer, Matthijs G.p. Feenstra, M.j.a. Botterblom, V. Korse, P. Te RieleAbstract:Abstract The course of postnatal development of noradrenaline (NA) and its unconjugated free metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), as well as the influence on early chronic vasopressin treatment, were investigated in various brain regions of the hereditary vasopressin-deficient (homozygous di/di) BRattleboro Rat. In addition, the densities of the adrenergic receptor subtypes were measured in adult brain. Brain NA levels of di/di pups appeared enhanced already at 7 days of age when compared with data of heterozygous (+/di) controls. This was also seen in areas not known to receive a vasopressinergic input, e.g. the frontal cortex. Levels of MHPG also differed between genotypes, but changes were slight and either a decrease or increase, depending on age and region tested. SatuRation analyses of α1-, α2-, and β-adrenoceptor binding on crude membrane prepaRations of some brain regions revealed no differences in adulthood. Chronic treatment with vasopressin between 6 and 13 days of age reduced the enhanced NA brain levels throughout the brain of the di/di BRattleboro pups. The known vasopressin-mediated enhancement of NA turnover in adult brain was also measurable in +/di pups of this neonatal period (MHPG/NA Ratios), indicating the early matuRation of the interaction of vasopressinergic and NAergic systems. However, the dose-response in the di/di BRattleboro Rat was biphasic with a decrease at a low dose of vasopressin. Since changes were found throughout the brain, it was concluded that vasopressin deficiency had altered the matuRation of NA neurons of the locus coeruleus which may be due to the absence of a presumed inhibitory control of vasopressin on synthesis and storage mechanisms at the perikaryal level.
-
Increased loss of brain DNA in the neonatal vasopressin-deficient BRattleboro Rat, but not in normal Rat treated with vasopressin antagonist.
Neuroscience Letters, 1993Co-Authors: G.j. Boer, F.g.m. Snijdewint, P. Te Riele, R. LichtAbstract:In order to establish whether vasopressin (VP) influences brain cell survival, [3H]thymidine was injected in 10-day-old vasopressin-deficient BRattleboro Rat pups, as well as in Wistar pups treated, neonatally, with the VP antagonist dP[Tyr(Me)2]VP followed by subsequent measurement of [3H]DNA in olfactory bulbs and cerebellum days and weeks thereafter. Results show, first of all, that the incorpoRation of [3H]thymidine into DNA was enhanced in the homozygous (HOM) BRattleboro, when compared with the heterozygous (HET; non-vasopressin-deficient) controls. The difference is due to the greater and prolonged tissue availability of [3H]thymidine, possibly pointing to an altered thymidine uptake and/or metabolism. Between postnatal days 25 and 39 no differences were seen in [3H]DNA content of the brain parts of the HET and Wistar control Rats. For the HOM Rats, however, a loss of [3H]DNA was seen (up to 8%), indicating that increased postnatal brain cell death might occur in the mutant. The antagonist treatment in Wistar Rat up to 21 days of age failed to show a similar effect. It is proposed that general growth impairments, Rather than VP receptor-mediated effects, lead to the brain cell loss.
Barbara Klausz - One of the best experts on this subject based on the ideXlab platform.
-
amelioRating schizophrenia like symptoms in vasopressin deficient male BRattleboro Rat by chronic antipsychotic treatment
European Journal of Pharmacology, 2021Co-Authors: Bibiana Torok, Barbara Klausz, Anna Fodor, Janos Tamas Varga, Dóra ZelenaAbstract:Abstract Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) BRattleboro Rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment effects of marketed antipsychotics are similar in di/di Rats to those seen in human schizophrenic patients. Chronic subcutaneous administRation of aripiprazole (5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.3 mg/kg) or risperidone (0.25 mg/kg) was used for 15 days in control (+/+ BRattleboro) and di/di Rats. Social discrimination, social avoidance and prepulse inhibition tests were conducted on day 1, 8 and 15 of the treatment. Vasopressin-deficient Rats showed social memory- and sensorimotor gating deficit. All used antipsychotics successfully normalized the reduced prepulse inhibition of di/di animals. However, most were effective only after prolonged treatment. Aripiprazole, clozapine, and olanzapine normalized the social memory deficit, while the effects of haloperidol and risperidone were not unequivocal. All drugs reduced social interest to some extent both in control and in di/di animals, aripiprazole being the less implicated in this regard during the social avoidance test. The restoRation of schizophrenia-like behavior by antipsychotic treatment further support the utility of the vasopressin-deficient BRattleboro Rat as a good preclinical model. Reduced social interest might be a general side-effect of antipsychotics, and aripiprazole has the most favorable profile in this regard.
-
The prepulse inhibition deficit appearance is largely independent on the circadian cycle, body weight, and the gender of vasopressin deficient BRattleboro Rat.
Endocrine regulations, 2016Co-Authors: Barbara Klausz, Anna Fodor, Blanka Tóth, Dóra ZelenaAbstract:OBJECTIVE A disturbance of sensorimotor gating measured by prepulse inhibition of acoustic startle (PPI) is one of the best tests of the schizophrenia-like behavior. Vasopressin was implicated in the development of schizophrenia; therefore, the naturally occurring vasopressin-deficient BRattleboro Rat has been suggested to be a reliable non-pharmacological animal model. However, previous studies focusing on PPI deficit did not use proper control and despite clear gender differences in the development of the disorder, the effect of gender has been mostly neglected. METHODS First, we compared the "noise" and "tone" type prepulse at 73-77-81 dB intensity during the light or dark phase using small (~150 g) or big (~500 g) Wistar Rats. The test parameters were validated by a pharmacological schizophrenia model (30 mg/kg ketamine i.p.). Than male, female, and lactating vasopressin-deficient animals were compared with +/+ ones. RESULTS We established that the prepulse "noise" type is not optimal for PPI testing. The cycle of the day as well as the body weight had no effect on PPI. Even if we compared vasopressin-deficient animals with their closely related +/+ controls, the PPI deficiency was visible with more pronounced effect at 77 dB prepulse intensity similarly to pharmacological schizophrenia model. Despite our expectation, the gender as well as lactation had no effect on the vasopressin-deficiency induced PPI deficit. CONCLUSIONS The present data confirmed and extended our previous studies that vasopressin-deficient Rat is a good model of schizophrenia. It seems that female as well as lactating BRattleboro Rats are useful tools for testing putative novel antipsychotics in line with special attention required for schizophrenic women.
-
increase in alzheimer s related markers preceeds memory disturbances studies in vasopressin deficient BRattleboro Rat
Brain Research Bulletin, 2014Co-Authors: Janos Varga, Barbara Klausz, Agnes Domokos, Sara Kalman, Magdolna Pakaski, Szabina Szűcs, Denes Garab, Agnes Zvara, Laszlo G Puskas, Janos KalmanAbstract:Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old Rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production. We compared adult (3 month) and old (12 month), normal and vasopressin-deficient BRattleboro Rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box). Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR. There was no difference between the memory of adult and aged groups. The vasopressin-deficient Rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them. Thus, the one year old Rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation.
-
the vasopressin deficient BRattleboro Rat lessons for the hypothalamo pituitary adrenal axis regulation
Cellular and Molecular Neurobiology, 2012Co-Authors: G B Makara, Ottó Pintér, István Barna, Barbara Klausz, Janos Varga, Dóra ZelenaAbstract:Adaptation to stress is indispensable to life and the hypothalamo–pituitary–adrenocortical axis is one of the major components of the adaptation. The hypothalamic component consists of corticotropin-releasing hormone and arginine vasopressin, with a questionable contribution of the latter. Vasopressin was more important in the regulation of the adrenocorticotropin secretion in the perinatal vasopressin-deficient BRattleboro Rats than in adulthood, where its role depended on the nature of the stressor encountered. In adults, the vasopressin deficiency did not influence the development of chronic stress response. In the neonatal Rats, the role of vasopressin was supported by the inhibitory action of a V1b antagonist and vasopressin antiserum. As the corticosterone response to stress did not follow the adrenocorticotropin levels, we assume the presence of an adrenocorticotropin independent adrenal gland regulation in the neonates. We have shown that the apparent dissociation of the corticosterone and adrenocorticotropin responses is not due to the different time course of the two hormone responses, to different level of the corticosterone binding globulin or to changes in the adrenal gland sensitivity. In vitro experiments point to the contribution of beta-adrenoceptors in the process. It was also confirmed by in vivo tests using the vasopressin-deficient BRattleboro pup as a model organism, where corticosterone levels may rise without adrenocorticotropin level changes. Another important question is the role of adrenocorticotropin beyond the corticosterone secretion regulation, which could be supposed, e.g., in cardiovascular events, immunological processes, and metabolism. We can conclude that BRattleboro Rats gave us much information about the stress-axis regulation far beyond the role of vasopressin itself.