7 recherche sur le mot-clé 'Behavior, Animal'

Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents / Renad JABARIN in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 41 p. Titre : Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents Type de document : Texte imprimé et/ou numérique Auteurs : Renad JABARIN, Auteur ; Shai NETSER, Auteur ; Shlomo WAGNER, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Animals  Humans  Rodentia  Autism Spectrum Disorder  Social Behavior  Behavior, Animal  Emotions  Animal models  Autism spectrum disorder  Behavioral phenotyping  Emotional states  Social vocalizations  Three-chamber test Index. décimale : PER Périodiques Résumé : MAIN: In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models of autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal social behavior create a bottleneck that significantly slows down progress in this field. Indeed, the bulk of research still relies on a small number of simple behavioral paradigms, the results of which are assessed without considering behavioral dynamics. Moreover, only few variables are examined in each paradigm, thus overlooking a significant portion of the complexity that characterizes social interaction between two conspecifics, subsequently hindering our understanding of the neural mechanisms governing different aspects of social behavior. We further demonstrate these constraints by discussing the most commonly used paradigm for assessing rodent social behavior, the three-chamber test. We also point to the fact that although emotions greatly influence human social behavior, we lack reliable means for assessing the emotional state of animals during social tasks. As such, we also discuss current evidence supporting the existence of pro-social emotions and emotional cognition in animal models. We further suggest that adequate social behavior analysis requires a novel multimodal approach that employs automated and simultaneous measurements of multiple behavioral and physiological variables at high temporal resolution in socially interacting animals. We accordingly describe several computerized systems and computational tools for acquiring and analyzing such measurements. Finally, we address several behavioral and physiological variables that can be used to assess socio-emotional states in animal models and thus elucidate intricacies of social behavior so as to attain deeper insight into the brain mechanisms that mediate such behaviors. CONCLUSIONS: In summary, we suggest that combining automated multimodal measurements with machine-learning algorithms will help define socio-emotional states and determine their dynamics during various types of social tasks, thus enabling a more thorough understanding of the complexity of social behavior. En ligne : http://dx.doi.org/10.1186/s13229-022-00521-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 [article] Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents [Texte imprimé et/ou numérique] / Renad JABARIN, Auteur ; Shai NETSER, Auteur ; Shlomo WAGNER, Auteur . - 41 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 41 p. Mots-clés : Animals  Humans  Rodentia  Autism Spectrum Disorder  Social Behavior  Behavior, Animal  Emotions  Animal models  Autism spectrum disorder  Behavioral phenotyping  Emotional states  Social vocalizations  Three-chamber test Index. décimale : PER Périodiques Résumé : MAIN: In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models of autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal social behavior create a bottleneck that significantly slows down progress in this field. Indeed, the bulk of research still relies on a small number of simple behavioral paradigms, the results of which are assessed without considering behavioral dynamics. Moreover, only few variables are examined in each paradigm, thus overlooking a significant portion of the complexity that characterizes social interaction between two conspecifics, subsequently hindering our understanding of the neural mechanisms governing different aspects of social behavior. We further demonstrate these constraints by discussing the most commonly used paradigm for assessing rodent social behavior, the three-chamber test. We also point to the fact that although emotions greatly influence human social behavior, we lack reliable means for assessing the emotional state of animals during social tasks. As such, we also discuss current evidence supporting the existence of pro-social emotions and emotional cognition in animal models. We further suggest that adequate social behavior analysis requires a novel multimodal approach that employs automated and simultaneous measurements of multiple behavioral and physiological variables at high temporal resolution in socially interacting animals. We accordingly describe several computerized systems and computational tools for acquiring and analyzing such measurements. Finally, we address several behavioral and physiological variables that can be used to assess socio-emotional states in animal models and thus elucidate intricacies of social behavior so as to attain deeper insight into the brain mechanisms that mediate such behaviors. CONCLUSIONS: In summary, we suggest that combining automated multimodal measurements with machine-learning algorithms will help define socio-emotional states and determine their dynamics during various types of social tasks, thus enabling a more thorough understanding of the complexity of social behavior. En ligne : http://dx.doi.org/10.1186/s13229-022-00521-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491

Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish / T. P. JOSEPH in Autism Research, 15-1 (January 2022)  

Public ISBD [article]  inAutism Research > 15-1 (January 2022) . - p.27-41 Titre : Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish Type de document : Texte imprimé et/ou numérique Auteurs : T. P. JOSEPH, Auteur ; F. ZHOU, Auteur ; L. Y. SAI, Auteur ; H. CHEN, Auteur ; S. L. LIN, Auteur ; M. SCHACHNER, Auteur Article en page(s) : p.27-41 Langues : Anglais (eng) Mots-clés : Animals  Anxiety/chemically induced/drug therapy  Autism Spectrum Disorder/drug therapy  Behavior, Animal  Disease Models, Animal  Duloxetine Hydrochloride  Prenatal Exposure Delayed Effects  Social Behavior  Social Interaction  Valproic Acid  Zebrafish  L1cam  autism spectrum disorder  duloxetine  social preference  valproic acid  zebrafish Index. décimale : PER Périodiques Résumé : Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose- and time-dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose-response experiments in zebrafish larvae, 10 ?M VPA exposure between 0.33 and 4.5?days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD-like phenotype in zebrafish. ASD-like elevated acetylcholine esterase (AChE) activity and reduced Akt-mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5-6 dpf) reduced the VPA-induced ASD-like phenotype in zebrafish larvae. Additionally, such early-life acute DLX treatment had long-term effects in ameliorating social impairments, hyperactivity, and anxiety-like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt-mTOR signaling. Overall, DLX treatment showed a long-term therapeutic effect on autistic-like behaviors, and alteration of AChE activity and Akt-mTOR signaling were identified as crucial in the VPA-induced ASD zebrafish model. En ligne : http://dx.doi.org/10.1002/aur.2620 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish [Texte imprimé et/ou numérique] / T. P. JOSEPH, Auteur ; F. ZHOU, Auteur ; L. Y. SAI, Auteur ; H. CHEN, Auteur ; S. L. LIN, Auteur ; M. SCHACHNER, Auteur . - p.27-41. Langues : Anglais (eng) in Autism Research > 15-1 (January 2022) . - p.27-41 Mots-clés : Animals  Anxiety/chemically induced/drug therapy  Autism Spectrum Disorder/drug therapy  Behavior, Animal  Disease Models, Animal  Duloxetine Hydrochloride  Prenatal Exposure Delayed Effects  Social Behavior  Social Interaction  Valproic Acid  Zebrafish  L1cam  autism spectrum disorder  duloxetine  social preference  valproic acid  zebrafish Index. décimale : PER Périodiques Résumé : Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose- and time-dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose-response experiments in zebrafish larvae, 10 ?M VPA exposure between 0.33 and 4.5?days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD-like phenotype in zebrafish. ASD-like elevated acetylcholine esterase (AChE) activity and reduced Akt-mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5-6 dpf) reduced the VPA-induced ASD-like phenotype in zebrafish larvae. Additionally, such early-life acute DLX treatment had long-term effects in ameliorating social impairments, hyperactivity, and anxiety-like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt-mTOR signaling. Overall, DLX treatment showed a long-term therapeutic effect on autistic-like behaviors, and alteration of AChE activity and Akt-mTOR signaling were identified as crucial in the VPA-induced ASD zebrafish model. En ligne : http://dx.doi.org/10.1002/aur.2620 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development / J. ELLEGOOD in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 25 p. Titre : Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development Type de document : Texte imprimé et/ou numérique Auteurs : J. ELLEGOOD, Auteur ; S. P. PETKOVA, Auteur ; A. KINMAN, Auteur ; L. R. QIU, Auteur ; A. ADHIKARI, Auteur ; A. A. WADE, Auteur ; D. FERNANDES, Auteur ; Z. LINDENMAIER, Auteur ; A. CREIGHTON, Auteur ; L. M. J. NUTTER, Auteur ; A. S. NORD, Auteur ; J. L. SILVERMAN, Auteur ; J. P. LERCH, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Mots-clés : Animals  Behavior, Animal  Brain/diagnostic imaging/growth & development  Exploratory Behavior  Fear  Female  Gait  Haploinsufficiency  Learning  Magnetic Resonance Imaging  Male  Mice, Mutant Strains  Motor Skills  Neurodevelopmental Disorders/diagnostic imaging/psychology  Recognition, Psychology  Social Behavior  Transcription Factors/genetics/metabolism  Vocalization, Animal  Arid1b  Autism  Behavior  Coffin–Siris syndrome  Magnetic resonance imaging  Mouse Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b(+/-) mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b(+/-) cerebellum. During neonatal development, Arid1b(+/-) mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b(+/-) mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b(+/-) mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b(+/-) mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b(+/-) haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs. En ligne : http://dx.doi.org/10.1186/s13229-021-00432-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development [Texte imprimé et/ou numérique] / J. ELLEGOOD, Auteur ; S. P. PETKOVA, Auteur ; A. KINMAN, Auteur ; L. R. QIU, Auteur ; A. ADHIKARI, Auteur ; A. A. WADE, Auteur ; D. FERNANDES, Auteur ; Z. LINDENMAIER, Auteur ; A. CREIGHTON, Auteur ; L. M. J. NUTTER, Auteur ; A. S. NORD, Auteur ; J. L. SILVERMAN, Auteur ; J. P. LERCH, Auteur . - 25 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 25 p. Mots-clés : Animals  Behavior, Animal  Brain/diagnostic imaging/growth & development  Exploratory Behavior  Fear  Female  Gait  Haploinsufficiency  Learning  Magnetic Resonance Imaging  Male  Mice, Mutant Strains  Motor Skills  Neurodevelopmental Disorders/diagnostic imaging/psychology  Recognition, Psychology  Social Behavior  Transcription Factors/genetics/metabolism  Vocalization, Animal  Arid1b  Autism  Behavior  Coffin–Siris syndrome  Magnetic resonance imaging  Mouse Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b(+/-) mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b(+/-) cerebellum. During neonatal development, Arid1b(+/-) mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b(+/-) mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b(+/-) mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b(+/-) mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b(+/-) haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs. En ligne : http://dx.doi.org/10.1186/s13229-021-00432-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder / C. NEWELL in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 37p. Titre : Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. NEWELL, Auteur ; M. R. BOMHOF, Auteur ; R. A. REIMER, Auteur ; D. S. HITTEL, Auteur ; J. M. RHO, Auteur ; J. SHEARER, Auteur Article en page(s) : 37p. Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/microbiology  Bacteria/isolation & purification  Behavior, Animal  Cecum/microbiology  Diet, Ketogenic  Disease Models, Animal  Feces/microbiology  Gastrointestinal Microbiome  Male  Mice  Mice, Inbred C57BL  Social Behavior  Autism spectrum disorder  BTBR mouse  Gut microbiome  Ketogenic diet Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model. En ligne : http://dx.doi.org/10.1186/s13229-016-0099-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder [Texte imprimé et/ou numérique] / C. NEWELL, Auteur ; M. R. BOMHOF, Auteur ; R. A. REIMER, Auteur ; D. S. HITTEL, Auteur ; J. M. RHO, Auteur ; J. SHEARER, Auteur . - 37p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 37p. Mots-clés : Animals  Autism Spectrum Disorder/microbiology  Bacteria/isolation & purification  Behavior, Animal  Cecum/microbiology  Diet, Ketogenic  Disease Models, Animal  Feces/microbiology  Gastrointestinal Microbiome  Male  Mice  Mice, Inbred C57BL  Social Behavior  Autism spectrum disorder  BTBR mouse  Gut microbiome  Ketogenic diet Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model. En ligne : http://dx.doi.org/10.1186/s13229-016-0099-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress / K. LUHACH in Autism Research, 14-11 (November 2021)  

Public ISBD [article]  inAutism Research > 14-11 (November 2021) . - p.2270-2286 Titre : Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress Type de document : Texte imprimé et/ou numérique Auteurs : K. LUHACH, Auteur ; G. T. KULKARNI, Auteur ; V. P. SINGH, Auteur ; B. SHARMA, Auteur Article en page(s) : p.2270-2286 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Behavior, Animal  Biomarkers  Disease Models, Animal  Doublecortin Protein  Female  Inflammation  Oxidative Stress  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Wistar  Valproic Acid  Vinca Alkaloids  Bdnf  doublecortin  phosphodiesterase  synapsin-IIa  valproic acid  vinpocetine Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-?) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-?, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. LAY SUMMARY: ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment. En ligne : http://dx.doi.org/10.1002/aur.2597 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress [Texte imprimé et/ou numérique] / K. LUHACH, Auteur ; G. T. KULKARNI, Auteur ; V. P. SINGH, Auteur ; B. SHARMA, Auteur . - p.2270-2286. Langues : Anglais (eng) in Autism Research > 14-11 (November 2021) . - p.2270-2286 Mots-clés : Animals  Autism Spectrum Disorder  Behavior, Animal  Biomarkers  Disease Models, Animal  Doublecortin Protein  Female  Inflammation  Oxidative Stress  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Wistar  Valproic Acid  Vinca Alkaloids  Bdnf  doublecortin  phosphodiesterase  synapsin-IIa  valproic acid  vinpocetine Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-?) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-?, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. LAY SUMMARY: ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment. En ligne : http://dx.doi.org/10.1002/aur.2597 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density / S. R. BERKOWICZ in Molecular Autism, 7 (2016)  

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Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development / S. HURLEY in Molecular Autism, 12 (2021)  

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