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Tsuyoshi Miyakawa - One of the best experts on this subject based on the ideXlab platform.
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Comprehensive Behavioral Analysis of Heterozygous Syngap1 Knockout Mice
Neuropsychopharmacology Reports, 2019Co-Authors: Ryuichi Nakajima, Hirotaka Shoji, Noboru H Komiyama, Keizo Takao, Seth G N Grant, Satoko Hattori, Tsuyoshi MiyakawaAbstract:Aims Synaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP1-related ID is estimated to account for at least 1% of ID cases. In mouse models with Syngap1 mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the Behavioral significance of the SYNGAP1 gene, we assessed various domains of behavior in Syngap1 heterozygous mutant mice using a Behavioral Test battery. Methods Male mice with a heterozygous mutation in the Syngap1 gene (Syngap1-/+ mice) created by Seth Grant's group were subjected to a battery of comprehensive Behavioral Tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T-maze, Y-maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple-hypothesis Testing, P-values below the false discovery rate calculated by the Benjamini-Hochberg method were considered as study-wide statistically significant. Results Syngap1-/+ mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in Syngap1 mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in Syngap1-/+ mice. Decreased anxiety-like behavior and depression-like behavior were noted, although increased locomotor activity is a potential confounding factor of these phenotypes. Increased home cage locomotor activity indicated hyperlocomotor activity not only in specific Behavioral Test conditions but also in familiar environments. Conclusion In Syngap1-/+ mice, we could reproduce most of the previously reported cognitive and emotional deficits. The decreased sensitivity to painful stimuli and impaired motor function that we found in Syngap1-/+ mice are consistent with the common characteristics of patients with SYNGAP-related ID. We further confirmed that the Syngap1 heterozygote mouse recapitulates the symptoms of ID and ASD patients.
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Distribution of Caskin1 protein and phenotypic characterization of its knockout mice using a comprehensive Behavioral Test battery.
Molecular brain, 2018Co-Authors: Tayo Katano, Tsuyoshi Miyakawa, Keizo Takao, Manabu Abe, Maya Yamazaki, Masahiko Watanabe, Kenji Sakimura, Seiji ItoAbstract:Calcium/calmodulin-dependent serine protein kinase (CASK)-interacting protein 1 (Caskin1) is a direct binding partner of the synaptic adaptor protein CASK. Because Caskin1 forms homo-multimers and binds not only CASK but also other neuronal proteins in vitro, it is anticipated to have neural functions; but its exact role in mammals remains unclear. Previously, we showed that the concentration of Caskin1 in the spinal dorsal horn increases under chronic pain. To characterize this protein, we generated Caskin1-knockout (Caskin1-KO) mice and specific anti-Caskin1 antibodies. Biochemical and immunohistochemical analyses demonstrated that Caskin1 was broadly distributed in the whole brain and spinal cord, and that it primarily localized at synapses. To elucidate the neural function of Caskin1 in vivo, we subjected Caskin1-KO mice to comprehensive Behavioral analysis. The mutant mice exhibited differences in gait, enhanced nociception, and anxiety-like behavior relative to their wild-type littermates. In addition, the knockouts exhibited strong freezing responses, with or without a cue tone, in contextual and cued-fear conditioning Tests as well as low memory retention in the Barnes Maze Test. Taken together, these results suggest that Caskin1 contributes to a wide spectrum of Behavioral phenotypes, including gait, nociception, memory, and stress response, in broad regions of the central nervous system.
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comprehensive Behavioral analysis of male ox1r mice showed implication of orexin receptor 1 in mood anxiety and social behavior
Frontiers in Behavioral Neuroscience, 2015Co-Authors: Md Golam Abbas, Hirotaka Shoji, Mari Hondo, Shingo Soya, Tsuyoshi Miyakawa, Takeshi SakuraiAbstract:Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system and autonomic nervous system. Here, we examined Ox1r-/- mice with a comprehensive Behavioral Test battery to screen additional OX1R functions. Ox1r-/- mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behaviour and sensory motor gating in addition to roles in mood and anxiety.
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comprehensive Behavioral phenotyping of calpastatin knockout mice
Molecular Brain, 2008Co-Authors: Ryuichi Nakajima, Nobuhisa Iwata, Shuming Huang, Jiro Takano, Tsuyoshi Miyakawa, Keizo TakaoAbstract:Background Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive Behavioral Test battery.
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selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion
Stroke, 2007Co-Authors: Masunari Shibata, Tsuyoshi Miyakawa, Nobuyuki Yamasaki, Rajesh N Kalaria, Youshi Fujita, Ryo Ohtani, Masafumi Ihara, Ryosuke Takahashi, Hidekazu TomimotoAbstract:Background and Purpose— We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The Behavioral characteristics of these mice were studied using a Test battery for neurological and cognitive functions. Methods— Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to Behavioral Test batteries. The first group underwent comprehensive Behavioral Test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze Test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze...
Keizo Takao - One of the best experts on this subject based on the ideXlab platform.
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Comprehensive Behavioral Analysis of Heterozygous Syngap1 Knockout Mice
Neuropsychopharmacology Reports, 2019Co-Authors: Ryuichi Nakajima, Hirotaka Shoji, Noboru H Komiyama, Keizo Takao, Seth G N Grant, Satoko Hattori, Tsuyoshi MiyakawaAbstract:Aims Synaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP1-related ID is estimated to account for at least 1% of ID cases. In mouse models with Syngap1 mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the Behavioral significance of the SYNGAP1 gene, we assessed various domains of behavior in Syngap1 heterozygous mutant mice using a Behavioral Test battery. Methods Male mice with a heterozygous mutation in the Syngap1 gene (Syngap1-/+ mice) created by Seth Grant's group were subjected to a battery of comprehensive Behavioral Tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T-maze, Y-maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple-hypothesis Testing, P-values below the false discovery rate calculated by the Benjamini-Hochberg method were considered as study-wide statistically significant. Results Syngap1-/+ mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in Syngap1 mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in Syngap1-/+ mice. Decreased anxiety-like behavior and depression-like behavior were noted, although increased locomotor activity is a potential confounding factor of these phenotypes. Increased home cage locomotor activity indicated hyperlocomotor activity not only in specific Behavioral Test conditions but also in familiar environments. Conclusion In Syngap1-/+ mice, we could reproduce most of the previously reported cognitive and emotional deficits. The decreased sensitivity to painful stimuli and impaired motor function that we found in Syngap1-/+ mice are consistent with the common characteristics of patients with SYNGAP-related ID. We further confirmed that the Syngap1 heterozygote mouse recapitulates the symptoms of ID and ASD patients.
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Distribution of Caskin1 protein and phenotypic characterization of its knockout mice using a comprehensive Behavioral Test battery.
Molecular brain, 2018Co-Authors: Tayo Katano, Tsuyoshi Miyakawa, Keizo Takao, Manabu Abe, Maya Yamazaki, Masahiko Watanabe, Kenji Sakimura, Seiji ItoAbstract:Calcium/calmodulin-dependent serine protein kinase (CASK)-interacting protein 1 (Caskin1) is a direct binding partner of the synaptic adaptor protein CASK. Because Caskin1 forms homo-multimers and binds not only CASK but also other neuronal proteins in vitro, it is anticipated to have neural functions; but its exact role in mammals remains unclear. Previously, we showed that the concentration of Caskin1 in the spinal dorsal horn increases under chronic pain. To characterize this protein, we generated Caskin1-knockout (Caskin1-KO) mice and specific anti-Caskin1 antibodies. Biochemical and immunohistochemical analyses demonstrated that Caskin1 was broadly distributed in the whole brain and spinal cord, and that it primarily localized at synapses. To elucidate the neural function of Caskin1 in vivo, we subjected Caskin1-KO mice to comprehensive Behavioral analysis. The mutant mice exhibited differences in gait, enhanced nociception, and anxiety-like behavior relative to their wild-type littermates. In addition, the knockouts exhibited strong freezing responses, with or without a cue tone, in contextual and cued-fear conditioning Tests as well as low memory retention in the Barnes Maze Test. Taken together, these results suggest that Caskin1 contributes to a wide spectrum of Behavioral phenotypes, including gait, nociception, memory, and stress response, in broad regions of the central nervous system.
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comprehensive Behavioral phenotyping of calpastatin knockout mice
Molecular Brain, 2008Co-Authors: Ryuichi Nakajima, Nobuhisa Iwata, Shuming Huang, Jiro Takano, Tsuyoshi Miyakawa, Keizo TakaoAbstract:Background Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive Behavioral Test battery.
Ryuichi Nakajima - One of the best experts on this subject based on the ideXlab platform.
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Comprehensive Behavioral Analysis of Heterozygous Syngap1 Knockout Mice
Neuropsychopharmacology Reports, 2019Co-Authors: Ryuichi Nakajima, Hirotaka Shoji, Noboru H Komiyama, Keizo Takao, Seth G N Grant, Satoko Hattori, Tsuyoshi MiyakawaAbstract:Aims Synaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP1-related ID is estimated to account for at least 1% of ID cases. In mouse models with Syngap1 mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the Behavioral significance of the SYNGAP1 gene, we assessed various domains of behavior in Syngap1 heterozygous mutant mice using a Behavioral Test battery. Methods Male mice with a heterozygous mutation in the Syngap1 gene (Syngap1-/+ mice) created by Seth Grant's group were subjected to a battery of comprehensive Behavioral Tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T-maze, Y-maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple-hypothesis Testing, P-values below the false discovery rate calculated by the Benjamini-Hochberg method were considered as study-wide statistically significant. Results Syngap1-/+ mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in Syngap1 mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in Syngap1-/+ mice. Decreased anxiety-like behavior and depression-like behavior were noted, although increased locomotor activity is a potential confounding factor of these phenotypes. Increased home cage locomotor activity indicated hyperlocomotor activity not only in specific Behavioral Test conditions but also in familiar environments. Conclusion In Syngap1-/+ mice, we could reproduce most of the previously reported cognitive and emotional deficits. The decreased sensitivity to painful stimuli and impaired motor function that we found in Syngap1-/+ mice are consistent with the common characteristics of patients with SYNGAP-related ID. We further confirmed that the Syngap1 heterozygote mouse recapitulates the symptoms of ID and ASD patients.
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comprehensive Behavioral phenotyping of calpastatin knockout mice
Molecular Brain, 2008Co-Authors: Ryuichi Nakajima, Nobuhisa Iwata, Shuming Huang, Jiro Takano, Tsuyoshi Miyakawa, Keizo TakaoAbstract:Background Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive Behavioral Test battery.
Anika M. S. Hartz - One of the best experts on this subject based on the ideXlab platform.
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a comprehensive Behavioral Test battery to assess learning and memory in 129s6 tg2576 mice
PLOS ONE, 2016Co-Authors: Andrea Wolf, Björn Bauer, Erin L. Abner, Anika M. S. Hartz, Tal AshkenazyfrolingerAbstract:Transgenic Tg2576 mice overexpressing human amyloid precursor protein (hAPP) are a widely used Alzheimer's disease (AD) mouse model to evaluate treatment effects on amyloid beta (Aβ) pathology and cognition. Tg2576 mice on a B6;SJL background strain carry a recessive rd1 mutation that leads to early retinal degeneration and visual impairment in homozygous carriers. This can impair performance in Behavioral Tests that rely on visual cues, and thus, affect study results. Therefore, B6;SJL/Tg2576 mice were systematically backcrossed with 129S6/SvEvTac mice resulting in 129S6/Tg2576 mice that lack the rd1 mutation. 129S6/Tg2576 mice do not develop retinal degeneration but still show Aβ accumulation in the brain that is comparable to the original B6;SJL/Tg2576 mouse. However, comprehensive studies on cognitive decline in 129S6/Tg2576 mice are limited. In this study, we used two dementia mouse models on a 129S6 background--scopolamine-treated 129S6/SvEvTac mice (3-5 month-old) and transgenic 129S6/Tg2576 mice (11-13 month-old)-to establish a Behavioral Test battery for assessing learning and memory. The Test battery consisted of five Tests to evaluate different aspects of cognitive impairment: a Y-Maze forced alternation task, a novel object recognition Test, the Morris water maze, the radial arm water maze, and a Y-maze spontaneous alternation task. We first established this Behavioral Test battery with the scopolamine-induced dementia model using 129S6/SvEvTac mice and then evaluated 129S6/Tg2576 mice using the same Testing protocol. Both models showed distinctive patterns of cognitive impairment. Together, the non-invasive Behavioral Test battery presented here allows detecting cognitive impairment in scopolamine-treated 129S6/SvEvTac mice and in transgenic 129S6/Tg2576 mice. Due to the modular nature of this Test battery, more Behavioral Tests, e.g. invasive assays to gain additional cognitive information, can easily be added.
Irwin Lucki - One of the best experts on this subject based on the ideXlab platform.
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the forced swimming Test as a model for core and component Behavioral effects of antidepressant drugs
Behavioural Pharmacology, 1997Co-Authors: Irwin LuckiAbstract:The existence of a number of classes of antidepressant drugs with diverse pharmacological effects would lead one to expect that antidepressant drugs acting through different pharmacological mechanisms should produce different Behavioral effects. Animal Behavioral Tests used to screen antidepressant drugs do not, however, discriminate between drugs that selectively enhance serotonin or norepinephrine transmission. Several components of human depression are differently affected by drugs selectively interacting with either serotonin or norepinephrine transmission. The ideal animal model for detecting antidepressant drug effects should thus be sensitive to all antidepressant drugs and should also display multiple components that are sensitive to specific drug classes. The revised scoring of the forced swimming Test corresponds to a Behavioral Test for antidepressant drugs that meet these criteria.