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Reduced brain volume and white matter alterations in Shank3-deficient rats / C. E. M. GOLDEN in Autism Research, 14-9 (September 2021)
[article]
Titre : Reduced brain volume and white matter alterations in Shank3-deficient rats Type de document : Texte imprimé et/ou numérique Auteurs : C. E. M. GOLDEN, Auteur ; V. X. WANG, Auteur ; Hala HARONY-NICOLAS, Auteur ; P. R. HOF, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : p.1837-1842 Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder Brain/anatomy & histology/diagnostic imaging Chromosome Disorders Diffusion Tensor Imaging Male Nerve Tissue Proteins/genetics Rats White Matter/anatomy & histology/diagnostic imaging Shank3 diffusion tensor imaging magnetic resonance imaging Index. décimale : PER Périodiques Résumé : Mutations and deletions in the SHANK3 gene cause the major neurodevelopmental features of Phelan-McDermid syndrome (PMS), which is characterized by intellectual disability, autism spectrum disorder, and sensory hyporeactivity. SHANK3 encodes a key structural component of excitatory synapses important for synaptogenesis. Clinical assessments and limited brain imaging studies of patients with PMS have uncovered regional volume reductions and white matter thinning. While these impairments have been replicated ex vivo in pups of a rat model, brain structure has not been assessed in rats in vivo or in adults. We assessed the brain structure of heterozygous and homozygous adult Shank3-deficient male rats in comparison to wild-type littermates with magnetic resonance imaging using both anatomical assessments and diffusion tensor imaging (DTI). Shank3-deficient rats showed a reduction in overall brain size and the absolute volume of the neocortex, piriform cortex, thalamus, forebrain, inferior and superior colliculi, internal capsule, and anterior commissure. The superior colliculus was decreased in relative volume. DTI revealed that axial diffusion and fractional anisotropy were reduced in the external capsule and mean diffusion was increased in the fornix, suggesting that restriction of diffusion perpendicular to the axis of the axonal fibers was impaired in these white matter tracts. Therefore, Shank3-deficient rats replicate the reduced brain volume and altered white matter phenotypes present in PMS. Our results indicate that the loss of a glutamatergic synaptic protein, Shank3, has structural consequences at the level of the whole brain. The brain regions that were altered represent potential cross-species structural biomarkers that warrant further study. En ligne : http://dx.doi.org/10.1002/aur.2568 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449
in Autism Research > 14-9 (September 2021) . - p.1837-1842[article] Reduced brain volume and white matter alterations in Shank3-deficient rats [Texte imprimé et/ou numérique] / C. E. M. GOLDEN, Auteur ; V. X. WANG, Auteur ; Hala HARONY-NICOLAS, Auteur ; P. R. HOF, Auteur ; Joseph D. BUXBAUM, Auteur . - p.1837-1842.
Langues : Anglais (eng)
in Autism Research > 14-9 (September 2021) . - p.1837-1842
Mots-clés : Animals Autism Spectrum Disorder Brain/anatomy & histology/diagnostic imaging Chromosome Disorders Diffusion Tensor Imaging Male Nerve Tissue Proteins/genetics Rats White Matter/anatomy & histology/diagnostic imaging Shank3 diffusion tensor imaging magnetic resonance imaging Index. décimale : PER Périodiques Résumé : Mutations and deletions in the SHANK3 gene cause the major neurodevelopmental features of Phelan-McDermid syndrome (PMS), which is characterized by intellectual disability, autism spectrum disorder, and sensory hyporeactivity. SHANK3 encodes a key structural component of excitatory synapses important for synaptogenesis. Clinical assessments and limited brain imaging studies of patients with PMS have uncovered regional volume reductions and white matter thinning. While these impairments have been replicated ex vivo in pups of a rat model, brain structure has not been assessed in rats in vivo or in adults. We assessed the brain structure of heterozygous and homozygous adult Shank3-deficient male rats in comparison to wild-type littermates with magnetic resonance imaging using both anatomical assessments and diffusion tensor imaging (DTI). Shank3-deficient rats showed a reduction in overall brain size and the absolute volume of the neocortex, piriform cortex, thalamus, forebrain, inferior and superior colliculi, internal capsule, and anterior commissure. The superior colliculus was decreased in relative volume. DTI revealed that axial diffusion and fractional anisotropy were reduced in the external capsule and mean diffusion was increased in the fornix, suggesting that restriction of diffusion perpendicular to the axis of the axonal fibers was impaired in these white matter tracts. Therefore, Shank3-deficient rats replicate the reduced brain volume and altered white matter phenotypes present in PMS. Our results indicate that the loss of a glutamatergic synaptic protein, Shank3, has structural consequences at the level of the whole brain. The brain regions that were altered represent potential cross-species structural biomarkers that warrant further study. En ligne : http://dx.doi.org/10.1002/aur.2568 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 Neuroglia in the autistic brain: evidence from a preclinical model / M. R. BRONZUOLI in Molecular Autism, 9 (2018)
[article]
Titre : Neuroglia in the autistic brain: evidence from a preclinical model Type de document : Texte imprimé et/ou numérique Auteurs : M. R. BRONZUOLI, Auteur ; R. FACCHINETTI, Auteur ; D. INGRASSIA, Auteur ; M. SARVADIO, Auteur ; S. SCHIAVI, Auteur ; L. STEARDO, Auteur ; A. VERKHRATSKY, Auteur ; V. TREZZA, Auteur ; C. SCUDERI, Auteur Article en page(s) : 66 p. Langues : Anglais (eng) Mots-clés : Animals Autistic Disorder/etiology/*pathology/physiopathology Brain/drug effects/*pathology Female Male Neuroglia/drug effects/*pathology Rats Rats, Wistar Stereotyped Behavior Valproic Acid/pharmacology/toxicity Vocalization, Animal *Astrocyte *Autism spectrum disorder *Microglia *Oligodendrocyte *Valproic acid of the Italian Ministry of Health (D.L. 26/2014) and with the European Parliament directive 2010/63/EU.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in which rats were exposed prenatally to antiepileptic and mood stabilizer drug valproic acid; this model being of acknowledged clinical relevance. Methods: We tested the autistic-like behaviors of valproic acid-prenatally exposed male rats by performing isolation-induced ultrasonic vocalizations, the three-chamber test, and the hole board test. To account for human infancy, adolescence, and adulthood, such tasks were performed at postnatal day 13, postnatal day 35, and postnatal day 90, respectively. After sacrifice, we examined gene and protein expression of specific markers of neuroglia in hippocampus, prefrontal cortex, and cerebellum, these brain regions being associated with autism spectrum disorder pathogenesis. Results: Infant offspring of VPA-exposed dams emitted less ultrasonic vocalizations when isolated from their mothers and siblings and, in adolescence and adulthood, they showed altered sociability in the three chamber test and increased stereotypic behavior in the hole board test. Molecular analyses indicate that prenatal valproic acid exposure affects all types of neuroglia, mainly causing transcriptional modifications. The most prominent changes occur in prefrontal cortex and in the hippocampus of autistic-like animals; these changes are particularly evident during infancy and adolescence, while they appear to be mitigated in adulthood. Conclusions: Neuroglial pathological phenotype in autism spectrum disorder rat model appears to be rather mild with little signs of widespread and chronic neuroinflammation. En ligne : https://dx.doi.org/10.1186/s13229-018-0254-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 9 (2018) . - 66 p.[article] Neuroglia in the autistic brain: evidence from a preclinical model [Texte imprimé et/ou numérique] / M. R. BRONZUOLI, Auteur ; R. FACCHINETTI, Auteur ; D. INGRASSIA, Auteur ; M. SARVADIO, Auteur ; S. SCHIAVI, Auteur ; L. STEARDO, Auteur ; A. VERKHRATSKY, Auteur ; V. TREZZA, Auteur ; C. SCUDERI, Auteur . - 66 p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 66 p.
Mots-clés : Animals Autistic Disorder/etiology/*pathology/physiopathology Brain/drug effects/*pathology Female Male Neuroglia/drug effects/*pathology Rats Rats, Wistar Stereotyped Behavior Valproic Acid/pharmacology/toxicity Vocalization, Animal *Astrocyte *Autism spectrum disorder *Microglia *Oligodendrocyte *Valproic acid of the Italian Ministry of Health (D.L. 26/2014) and with the European Parliament directive 2010/63/EU.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in which rats were exposed prenatally to antiepileptic and mood stabilizer drug valproic acid; this model being of acknowledged clinical relevance. Methods: We tested the autistic-like behaviors of valproic acid-prenatally exposed male rats by performing isolation-induced ultrasonic vocalizations, the three-chamber test, and the hole board test. To account for human infancy, adolescence, and adulthood, such tasks were performed at postnatal day 13, postnatal day 35, and postnatal day 90, respectively. After sacrifice, we examined gene and protein expression of specific markers of neuroglia in hippocampus, prefrontal cortex, and cerebellum, these brain regions being associated with autism spectrum disorder pathogenesis. Results: Infant offspring of VPA-exposed dams emitted less ultrasonic vocalizations when isolated from their mothers and siblings and, in adolescence and adulthood, they showed altered sociability in the three chamber test and increased stereotypic behavior in the hole board test. Molecular analyses indicate that prenatal valproic acid exposure affects all types of neuroglia, mainly causing transcriptional modifications. The most prominent changes occur in prefrontal cortex and in the hippocampus of autistic-like animals; these changes are particularly evident during infancy and adolescence, while they appear to be mitigated in adulthood. Conclusions: Neuroglial pathological phenotype in autism spectrum disorder rat model appears to be rather mild with little signs of widespread and chronic neuroinflammation. En ligne : https://dx.doi.org/10.1186/s13229-018-0254-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 Postweaning positive modulation of ?5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner / Anja SANTRAC in Autism Research, 15-5 (May 2022)
[article]
Titre : Postweaning positive modulation of ?5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner Type de document : Texte imprimé et/ou numérique Auteurs : Anja SANTRAC, Auteur ; Dunja BIJELIC, Auteur ; Vladimir STEVANOVI?, Auteur ; Marija BANI?EVI?, Auteur ; Jovana ARAN?ELOVI?, Auteur ; Bojan BATINI?, Auteur ; Dishary SHARMIN, Auteur ; James M. COOK, Auteur ; Miroslav M. SAVI?, Auteur Article en page(s) : p.806-820 Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/chemically induced/drug therapy Autistic Disorder Behavior, Animal/physiology Calcium/metabolism/pharmacology Disease Models, Animal Female Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Receptors, GABA-A/metabolism Social Behavior Valproic Acid/pharmacology gamma-Aminobutyric Acid Kcc2 Nkcc1 autism spectrum disorder neuron maturity valproic acid animal model ?5GABAA receptor Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD), as a common neurodevelopmental disorder that encompasses impairments in social communication and interaction, as well as repetitive and restrictive behavior, still awaits an effective treatment strategy. The involvement of GABAergic neurotransmission, and especially a deficit of GABA(A) receptors that contain the ?5 subunits, were implicated in pathogenesis of ASD. Therefore, we tested MP-III-022, a positive allosteric modulator (PAM) selective for ?5GABAA receptors, in Wistar rats prenatally exposed to valproic acid, as an animal model useful for studying ASD. Postweaning rats of both sexes were treated for 7?days with vehicle or MP-III-022 at two doses pharmacokinetically determined as selective, and thereafter tested in a behavioral battery (social interaction test, elevated plus maze, spontaneous locomotor activity, and standard and reverse Morris water maze). Additional rats were used for establishing a primary neuronal culture and performing calcium imaging, and determination of hippocampal mRNA levels of GABRA5, NKCC1, and KCC2. MP-III-022 prevented impairments in many parameters connected with social, repetitive and restrictive behavioral domains. The lower and higher dose was more effective in males and females, respectively. Intriguingly, MP-III-022 elicited certain changes in control animals similar to those manifested in valproate animals themselves. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, assessed with calcium imaging, and also in expression changes of three genes analyzed. Our data support a role of ?5GABAA receptors in pathophysiology of ASD, and suggest a potential application of selective PAMs in its treatment, that needs to be researched in a sex-specific manner. LAY SUMMARY: In rats prenatally exposed to valproate as a model of autism, a modulator of ?5GABAA receptors ameliorated social, repetitive and restrictive impairments, and, intriguingly, elicited certain autism-like changes in control rats. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, and partly in gene expression changes. This shows a role of ?5GABAA receptors in pathophysiology of ASD, and a potential application of their selective modulators in its treatment. En ligne : http://dx.doi.org/10.1002/aur.2699 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473
in Autism Research > 15-5 (May 2022) . - p.806-820[article] Postweaning positive modulation of ?5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner [Texte imprimé et/ou numérique] / Anja SANTRAC, Auteur ; Dunja BIJELIC, Auteur ; Vladimir STEVANOVI?, Auteur ; Marija BANI?EVI?, Auteur ; Jovana ARAN?ELOVI?, Auteur ; Bojan BATINI?, Auteur ; Dishary SHARMIN, Auteur ; James M. COOK, Auteur ; Miroslav M. SAVI?, Auteur . - p.806-820.
Langues : Anglais (eng)
in Autism Research > 15-5 (May 2022) . - p.806-820
Mots-clés : Animals Autism Spectrum Disorder/chemically induced/drug therapy Autistic Disorder Behavior, Animal/physiology Calcium/metabolism/pharmacology Disease Models, Animal Female Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Receptors, GABA-A/metabolism Social Behavior Valproic Acid/pharmacology gamma-Aminobutyric Acid Kcc2 Nkcc1 autism spectrum disorder neuron maturity valproic acid animal model ?5GABAA receptor Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD), as a common neurodevelopmental disorder that encompasses impairments in social communication and interaction, as well as repetitive and restrictive behavior, still awaits an effective treatment strategy. The involvement of GABAergic neurotransmission, and especially a deficit of GABA(A) receptors that contain the ?5 subunits, were implicated in pathogenesis of ASD. Therefore, we tested MP-III-022, a positive allosteric modulator (PAM) selective for ?5GABAA receptors, in Wistar rats prenatally exposed to valproic acid, as an animal model useful for studying ASD. Postweaning rats of both sexes were treated for 7?days with vehicle or MP-III-022 at two doses pharmacokinetically determined as selective, and thereafter tested in a behavioral battery (social interaction test, elevated plus maze, spontaneous locomotor activity, and standard and reverse Morris water maze). Additional rats were used for establishing a primary neuronal culture and performing calcium imaging, and determination of hippocampal mRNA levels of GABRA5, NKCC1, and KCC2. MP-III-022 prevented impairments in many parameters connected with social, repetitive and restrictive behavioral domains. The lower and higher dose was more effective in males and females, respectively. Intriguingly, MP-III-022 elicited certain changes in control animals similar to those manifested in valproate animals themselves. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, assessed with calcium imaging, and also in expression changes of three genes analyzed. Our data support a role of ?5GABAA receptors in pathophysiology of ASD, and suggest a potential application of selective PAMs in its treatment, that needs to be researched in a sex-specific manner. LAY SUMMARY: In rats prenatally exposed to valproate as a model of autism, a modulator of ?5GABAA receptors ameliorated social, repetitive and restrictive impairments, and, intriguingly, elicited certain autism-like changes in control rats. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, and partly in gene expression changes. This shows a role of ?5GABAA receptors in pathophysiology of ASD, and a potential application of their selective modulators in its treatment. En ligne : http://dx.doi.org/10.1002/aur.2699 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473 The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism / F. LIU in Molecular Autism, 9 (2018)
[article]
Titre : The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism Type de document : Texte imprimé et/ou numérique Auteurs : F. LIU, Auteur ; K. HORTON-SPARKS, Auteur ; V. HULL, Auteur ; R. W. LI, Auteur ; V. MARTINEZ-CERDENO, Auteur Article en page(s) : 61 p. Langues : Anglais (eng) Mots-clés : Animals Autistic Disorder/etiology/*microbiology Bacterial Typing Techniques Disease Models, Animal Dysbiosis/etiology/*microbiology *Gastrointestinal Microbiome Rats Rats, Sprague-Dawley Valproic Acid/administration & dosage/toxicity Index. décimale : PER Périodiques Résumé : Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Fecal samples from the rectum were collected at necropsy, microbial total DNA was extracted, 16 rRNA genes sequenced using Illumina, and the global microbial co-occurrence network was constructed using a random matrix theory-based pipeline. Collected rat microbiome data were compared to available data derived from cases of autism. Results: We found that VPA administration during pregnancy reduced fecal microbial richness, changed the gut microbial composition, and altered the metabolite potential of the fecal microbial community in a pattern similar to that seen in patients with ASD. However, the global network property and network composition as well as microbial co-occurrence patterns were largely preserved in the offspring of rats exposed to prenatal administration of VPA. Conclusions: Our data on the microbiota of the VPA rat model of autism indicate that this model, in addition to behaviorally and anatomically mimicking the autistic brain as previously shown, also mimics the microbiome features of autism, making it one of the best-suited rodent models for the study of autism and ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0251-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 9 (2018) . - 61 p.[article] The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism [Texte imprimé et/ou numérique] / F. LIU, Auteur ; K. HORTON-SPARKS, Auteur ; V. HULL, Auteur ; R. W. LI, Auteur ; V. MARTINEZ-CERDENO, Auteur . - 61 p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 61 p.
Mots-clés : Animals Autistic Disorder/etiology/*microbiology Bacterial Typing Techniques Disease Models, Animal Dysbiosis/etiology/*microbiology *Gastrointestinal Microbiome Rats Rats, Sprague-Dawley Valproic Acid/administration & dosage/toxicity Index. décimale : PER Périodiques Résumé : Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Fecal samples from the rectum were collected at necropsy, microbial total DNA was extracted, 16 rRNA genes sequenced using Illumina, and the global microbial co-occurrence network was constructed using a random matrix theory-based pipeline. Collected rat microbiome data were compared to available data derived from cases of autism. Results: We found that VPA administration during pregnancy reduced fecal microbial richness, changed the gut microbial composition, and altered the metabolite potential of the fecal microbial community in a pattern similar to that seen in patients with ASD. However, the global network property and network composition as well as microbial co-occurrence patterns were largely preserved in the offspring of rats exposed to prenatal administration of VPA. Conclusions: Our data on the microbiota of the VPA rat model of autism indicate that this model, in addition to behaviorally and anatomically mimicking the autistic brain as previously shown, also mimics the microbiome features of autism, making it one of the best-suited rodent models for the study of autism and ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0251-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 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)
[article]
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
in Autism Research > 14-11 (November 2021) . - p.2270-2286[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 Cerebellar demyelination and neurodegeneration associated with mTORC1 hyperactivity may contribute to the developmental onset of autism-like neurobehavioral phenotype in a rat model / Viera KUTNA in Autism Research, 15-5 (May 2022)
PermalinkExperience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome / Antonis ASIMINAS in Molecular Autism, 13 (2022)
PermalinkImbalance of flight-freeze responses and their cellular correlates in the Nlgn3(-/y) rat model of autism / Natasha J. ANSTEY in Molecular Autism, 13 (2022)
PermalinkOverexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment / A. BANERJEE in Molecular Autism, 7 (2016)
PermalinkTiming and Intertemporal Choice Behavior in the Valproic Acid Rat Model of Autism Spectrum Disorder / William E. DECOTEAU in Journal of Autism and Developmental Disorders, 52-6 (June 2022)
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