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Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders / M. E. TRAETTA in Molecular Autism, 12 (2021)
[article]
Titre : Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. E. TRAETTA, Auteur ; M. G. CODAGNONE, Auteur ; N. A. UCCELLI, Auteur ; A. J. RAMOS, Auteur ; S. ZÁRATE, Auteur ; A. REINÉS, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Mots-clés : Animals Anticonvulsants Autism Spectrum Disorder/chemically induced/metabolism Behavior, Animal/drug effects Cells, Cultured Disease Models, Animal Female Hippocampus/drug effects/metabolism/ultrastructure Male Microglia/drug effects Neural Cell Adhesion Molecules/metabolism Neuronal Plasticity/drug effects Neurons/drug effects/metabolism/ultrastructure Phosphoprotein Phosphatases/metabolism Pregnancy Rats, Wistar Synapses/drug effects Valproic Acid Adhesion molecules Autism spectrum disorders Hippocampus Ncam Synapse VPA model Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. METHODS: Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. RESULTS: At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. CONCLUSIONS: Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model. En ligne : http://dx.doi.org/10.1186/s13229-021-00428-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 23 p.[article] Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders [Texte imprimé et/ou numérique] / M. E. TRAETTA, Auteur ; M. G. CODAGNONE, Auteur ; N. A. UCCELLI, Auteur ; A. J. RAMOS, Auteur ; S. ZÁRATE, Auteur ; A. REINÉS, Auteur . - 23 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 23 p.
Mots-clés : Animals Anticonvulsants Autism Spectrum Disorder/chemically induced/metabolism Behavior, Animal/drug effects Cells, Cultured Disease Models, Animal Female Hippocampus/drug effects/metabolism/ultrastructure Male Microglia/drug effects Neural Cell Adhesion Molecules/metabolism Neuronal Plasticity/drug effects Neurons/drug effects/metabolism/ultrastructure Phosphoprotein Phosphatases/metabolism Pregnancy Rats, Wistar Synapses/drug effects Valproic Acid Adhesion molecules Autism spectrum disorders Hippocampus Ncam Synapse VPA model Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. METHODS: Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. RESULTS: At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. CONCLUSIONS: Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model. En ligne : http://dx.doi.org/10.1186/s13229-021-00428-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 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 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 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