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Thomas M Burbacher - One of the best experts on this subject based on the ideXlab platform.
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preclinical modeling of exposure to a global marine bio contaminant effects of in utero domoic acid exposure on neonatal behavior and infant Memory
Neurotoxicology and Teratology, 2019Co-Authors: Kimberly S Grant, Brenda Crouthamel, Caroline Kenney, Noelle Mckain, Rebekah Petroff, Sara Shum, Jing Jing, Nina Isoherranen, Thomas M BurbacherAbstract:Abstract Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the Recognition Memory assessment, given between 1 and 2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult Recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential Visual attention to novel test stimuli. This finding suggests subtle but significant impairment in Recognition Memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.
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preclinical modeling of exposure to a global marine bio contaminant effects of in utero domoic acid exposure on neonatal behavior and infant Memory
bioRxiv, 2018Co-Authors: Kimberly S Grant, Brenda Crouthamel, Caroline Kenney, Noelle Mckain, Rebekah Petroff, Sara Shum, Jing Jing, Nina Isoherranen, Thomas M BurbacherAbstract:Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate behavioral development during early infancy, offspring were administered a neonatal exam modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems. Results indicated that DA does not impact early survival reflexes or responsivity to the environment during the neonatal period. Findings from Recognition Memory tests showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. However, infants in the 0.15 mg/kg DA group failed to demonstrate a novelty response when problems became more challenging. This study is the first to evaluate the offspring neurodevelopmental effects of prenatal DA exposure in a translational primate model and results indicate subtle but significant consequences on emerging Memory processes.
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measuring infant Memory utility of the Visual paired comparison test paradigm for studies in developmental neurotoxicology
Neurotoxicology and Teratology, 2012Co-Authors: Thomas M Burbacher, Kimberly S GrantAbstract:The assessment of brain function and behavior in young infants is central to understanding the effects of chemical exposure on central nervous system development. One approach to infant cognitive assessment, based on the direct observation of infant eye movements, is known as the Visual Paired-Comparison task. The Visual Paired-Comparison test methodology uses selective Visual attention as a vehicle to study emerging Recognition Memory skills. The utility of this procedure to study Visual Recognition Memory has been well established in both human and nonhuman primate infants. The primary outcome measure produced by this assessment technique is known as the Novelty Preference Score, reflecting the amount of time the infant spends actively looking at novel rather than familiar test stimuli. Visual Recognition Memory testing has demonstrated a strong sensitivity to conditions that may place infants at risk for poor developmental outcome (e.g. preterm birth, Down syndrome) and in humans; performance is significantly related to later measures of I.Q. and language competency. This assessment methodology has been successfully applied to the study of neurobehavioral effects after fetal neurotoxicant exposure. Field and laboratory studies have used tests of Visual Recognition Memory to better understand the effects of compounds such as lead, methylmercury and polychlorinated biphenyls on emergent cognitive processing. The Visual Paired-Comparison paradigm and its capacity to measure Recognition Memory in preverbal infants provides a valid and theoretically meaningful approach to neurobehavioral assessment for studies in developmental toxicology and teratology.
Kimberly S Grant - One of the best experts on this subject based on the ideXlab platform.
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preclinical modeling of exposure to a global marine bio contaminant effects of in utero domoic acid exposure on neonatal behavior and infant Memory
Neurotoxicology and Teratology, 2019Co-Authors: Kimberly S Grant, Brenda Crouthamel, Caroline Kenney, Noelle Mckain, Rebekah Petroff, Sara Shum, Jing Jing, Nina Isoherranen, Thomas M BurbacherAbstract:Abstract Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the Recognition Memory assessment, given between 1 and 2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult Recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential Visual attention to novel test stimuli. This finding suggests subtle but significant impairment in Recognition Memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.
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preclinical modeling of exposure to a global marine bio contaminant effects of in utero domoic acid exposure on neonatal behavior and infant Memory
bioRxiv, 2018Co-Authors: Kimberly S Grant, Brenda Crouthamel, Caroline Kenney, Noelle Mckain, Rebekah Petroff, Sara Shum, Jing Jing, Nina Isoherranen, Thomas M BurbacherAbstract:Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate behavioral development during early infancy, offspring were administered a neonatal exam modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems. Results indicated that DA does not impact early survival reflexes or responsivity to the environment during the neonatal period. Findings from Recognition Memory tests showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. However, infants in the 0.15 mg/kg DA group failed to demonstrate a novelty response when problems became more challenging. This study is the first to evaluate the offspring neurodevelopmental effects of prenatal DA exposure in a translational primate model and results indicate subtle but significant consequences on emerging Memory processes.
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measuring infant Memory utility of the Visual paired comparison test paradigm for studies in developmental neurotoxicology
Neurotoxicology and Teratology, 2012Co-Authors: Thomas M Burbacher, Kimberly S GrantAbstract:The assessment of brain function and behavior in young infants is central to understanding the effects of chemical exposure on central nervous system development. One approach to infant cognitive assessment, based on the direct observation of infant eye movements, is known as the Visual Paired-Comparison task. The Visual Paired-Comparison test methodology uses selective Visual attention as a vehicle to study emerging Recognition Memory skills. The utility of this procedure to study Visual Recognition Memory has been well established in both human and nonhuman primate infants. The primary outcome measure produced by this assessment technique is known as the Novelty Preference Score, reflecting the amount of time the infant spends actively looking at novel rather than familiar test stimuli. Visual Recognition Memory testing has demonstrated a strong sensitivity to conditions that may place infants at risk for poor developmental outcome (e.g. preterm birth, Down syndrome) and in humans; performance is significantly related to later measures of I.Q. and language competency. This assessment methodology has been successfully applied to the study of neurobehavioral effects after fetal neurotoxicant exposure. Field and laboratory studies have used tests of Visual Recognition Memory to better understand the effects of compounds such as lead, methylmercury and polychlorinated biphenyls on emergent cognitive processing. The Visual Paired-Comparison paradigm and its capacity to measure Recognition Memory in preverbal infants provides a valid and theoretically meaningful approach to neurobehavioral assessment for studies in developmental toxicology and teratology.
Thomas G Aigner - One of the best experts on this subject based on the ideXlab platform.
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fk960 n 4 acetyl 1 piperazinyl p fluorobenzamide monohydrate a novel potential antidementia drug improves Visual Recognition Memory in rhesus monkeys comparison with physostigmine
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: Nobuya Matsuoka, Thomas G AignerAbstract:Our previous studies demonstrated that FK960 [ N -(4-acetyl-1-piperazinyl)- p -fluorobenzamide monohydrate], a novel antidementia piperazine derivative, exerts beneficial effects on Memory deficits in various rodent models of amnesia, through activation of the somatostatin neuronal system. To extend the antiamnesic action of FK960 to nonhuman primates, FK960 was evaluated for its ability to reverse the deficits in Visual Recognition Memory produced by muscarinic cholinergic receptor blockade by scopolamine or N -methyl-d-aspartate receptor blockade by dizocilpine (MK-801) in four rhesus monkeys performing a computer-automated version of delayed nonmatching to sample, with a list length of 20 trial-unique graphic symbols. Furthermore, the effects of FK960 were compared with those of physostigmine, a cholinesterase inhibitor. Doses of FK960 (1, 3.2, 10, 32, 100, 320 or 1000 μg/kg) injected i.m. 30 min before testing minimally affected Visual Recognition Memory when administered alone. FK960 (1, 3.2, 10 or 32 μg/kg) significantly antagonized the deficits in Visual Recognition Memory produced by scopolamine (10 μg/kg); the same doses of the drug minimally affected the deficits produced by dizocilpine (32 μg/kg). Similarly, physostigmine (3.2, 10 or 32 μg/kg) significantly and dose-dependently restored the Visual Recognition Memory deficits produced by scopolamine (10 μg/kg) but not those produced by dizocilpine (32 μg/kg). From these results, we conclude that FK960 improves deficits in Recognition Memory associated with central cholinergic hypofunction in nonhuman primates, and we suggest that the therapeutic potential of this drug for patients with dementia should be evaluated.
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the glycine nmda receptor antagonist ha 966 impairs Visual Recognition Memory in rhesus monkeys
Brain Research, 1996Co-Authors: Nobuya Matsuoka, Thomas G AignerAbstract:Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-D-asparate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on Visual Recognition Memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1-10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the Memory deficity following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in Recognition Memory were observed following treatment with MK-801, though at much lower doses (3.2-32 micrograms/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 micrograms/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 micrograms/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the Recognition Memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex.
Jocelyne Bachevalier - One of the best experts on this subject based on the ideXlab platform.
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the hippocampal parahippocampal regions and Recognition Memory insights from Visual paired comparison versus object delayed nonmatching in monkeys
The Journal of Neuroscience, 2004Co-Authors: Sarah Nemanic, Maria C Alvarado, Jocelyne BachevalierAbstract:Recognition Memory was assessed by submitting the same adult monkeys to Visual paired comparison (VPC) with mixed delays (10-120 sec), followed by three consecutive versions of object-delayed nonmatching-to-sample (DNMS): increasing delays (10-600 sec), lengthened lists (3-10 objects), and intervening distractors in the delays (light at 10 sec, motor task at 30-600 sec, or context change at 600 sec). Four groups were tested: normal controls, monkeys with ibotenic acid lesions of the hippocampal formation (H), and monkeys with aspiration lesions of either the perirhinal (PRh) or parahippocampal (areas TH/TF) cortex. Group H was impaired on VPC at delays ≥60 sec but had difficulty on DNMS only at 600 sec delays with distraction. In group TH/TF, the VPC impairment emerged earlier (30 sec); yet, once the nonmatching rule was mastered, no significant change occurred on any DNMS condition. Only group PRh behaved congruently on VPC and DNMS, exhibiting a deficit at the easiest condition that worsened with increasing delays as well as in DNMS lengthened list and distraction conditions. These results led us to postulate that VPC and DNMS, as previously administered to monkeys, were not equivalent Visual Recognition Memory probes. Specifically, we propose that, for VPC, because of passive (incidental) encoding, the animal's performance rests on both item familiarity and event recollection, whereas, for DNMS, because of active (purposeful) encoding, performance relies more on item familiarity. This proposal converges with current models postulating distinct, but interactive, mnemonic roles for the hippocampal and adjacent TH/TF regions.
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neonatal aspiration lesions of the hippocampal formation impair Visual Recognition Memory when assessed by paired comparison task but not by delayed nonmatching to sample task
Hippocampus, 1999Co-Authors: Olivier Pascalis, Jocelyne BachevalierAbstract:Previous experiments showed that neonatal aspiration lesions of the hippocampal formation in monkeys yield no Visual Recognition loss at delays up to 10 min, when Recognition Memory was assessed by a trial-unique delayed nonmatching-to-sample (DNMS) task. The present study examined whether neonatal hippocampal lesions also have no effect on Visual Recognition when assessed by a Visual paired-comparison (VPC) task. In the VPC task, animals are looking at Visual stimuli and their preference for viewing new stimuli is measured. Normal adult monkeys showed strong preference for looking at the novel stimuli at all delays tested. By contrast, adult monkeys with neonatal hippocampal lesions, which included the dentate gyrus, cornus ammon (CA) fields, subicular complex, and portions of parahippocampal areas TH/TF, showed preference for novelty at short delays of 10 s but not at longer delays of 30 s to 24 h. This Visual Recognition loss contrasts with the normal performance of the same operated animals when tested in the DNMS task. The discrepancy between the results obtained in the two Recognition tasks suggests that, to perform normally on the DNMS task, the operated monkeys may have used behavioral strategies that do not depend on the integrity of the hippocampal formation. In this respect, VPC appears to be a more sensitive task than DNMS to detect damage to the hippocampal region in primates. Hippocampus 1999;9:609–616. © 1999 Wiley-Liss, Inc.
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a comparison of children s performance on two Recognition Memory tasks delayed nonmatch to sample versus Visual paired comparison
Developmental Psychobiology, 1993Co-Authors: William H Overman, Jocelyne Bachevalier, Frank Sewell, Jana DrewAbstract:Although 4- to 6-month-old children have a significant tendency to look at new stimuli in a Visual paired-comparison task (VPC), they have difficulty in consistently choosing novel objects in a delayed nonmatch-to-sample task (DNMS). To evaluate which factors could account for this difficulty, we tested human infants (10–107 months) and adults (17–25 years) in a DNMS task while monitoring eye fixations. The results indicated that children at all ages reliably looked at (VPC scores) or chose (DNMS scores) the new stimuli about 60% of the time, indicating that both tasks measure Visual Recognition Memory. A videotape analysis of Visual attention revealed that children younger than 22 months, but not older children, spent significanlty more time Visually exploring the objects rather than looking at the food reward under it. Although this Visual attraction to objects in children younger than 22 months of age may have impaired the formation of stimulus-reinforcer association needed to solve the DNMS task, this was not the case for older children, since beyond 22 months of age children consistently looked at the reward while displacing the objects. These results suggest that other cognitive abilities required by the DNMS task may not be fully functional even in children 22 months and older. © 1993 John Wiley & Sons, Inc.
Fernando Rodríguez De Fonseca - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves Memory and changes the phenotype of hippocampal microglia despite ethanol exposure.
Biochemical Pharmacology, 2018Co-Authors: Patricia Rivera, Francisco Javier Pavón, Antonia Serrano, María Del Mar Fernández-arjona, Daniel Silva-peña, Eduardo Blanco, Antonio Vargas, María Dolores López-Ávalos, Jesús M. Grondona, Fernando Rodríguez De FonsecaAbstract:Changes in endogenous cannabinoid homeostasis are associated with both ethanol-related neuroinflammation and Memory decline. Extensive research is still required to unveil the role of endocannabinoid signaling activation on hippocampal microglial cells after ethanol exposure. Either microglial morphology, phenotype and recruitment may become notably altered after chronic alcohol-related neurodegeneration. Here, we evaluated the pharmacological effects of fatty-acid amide-hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg), oleoylethanolamide (OEA, 10 mg/kg), arachidonoylethanolamide (AEA, 10 mg/kg), the CB1 receptor agonist ACEA (3 mg/kg) and the CB2 receptor agonist JWH133 (0.2 mg/kg) administered for 5 days in a rat model of subchronic (2 weeks) ethanol diet (11% v/v) exposure. URB597 turned to be the most effective treatment. URB597 increased microglial (IBA-1+) cell population, and changed morphometric features (cell area and perimeter, roughness, fractal dimension, lacunarity) associated with activated microglia in the hippocampus of ethanol-exposed rats. Regarding innate immune activity, URB597 specifically increased mRNA levels of toll-like receptor 4 (TLR4), glial fibrillary acidic protein (Gfap) and the chemokine stromal cell-derived factor 1 (SDF-1α/CXCL12), and elevated the cell population expressing the chemokine receptors CX3CR1, CCR2 and CCR4 in the ethanol-exposed rat hippocampus. Contrary to ethanol effect, URB597 reduced mRNA levels of Iba-1, Tnfα, IL-6 and the monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as cell population expressing iNOS. URB597 effects on hippocampal immune system were accompanied by changes in short and long-term Visual Recognition Memory. These results suggest that FAAH inhibition may modulates hippocampal microglial recruitment and activation that can be associated with improved hippocampal-dependent Memory despite ethanol exposure.
