Prenatal Exposure to Valproic Acid Affects Microglia and Synaptic Ultrastructure in a Brain-Region-Specific Manner in Young-Adult Male Rats: Relevance to Autism Spectrum Disorders

Autor: Magdalena Gewartowska, Lidia Babiec, Grzegorz A. Czapski, Agnieszka Dominiak, Agata Adamczyk, Rafał Polowy, Robert K. Filipkowski, Magdalena Gąssowska-Dobrowolska, Małgorzata Frontczak-Baniewicz, Henryk Jęśko, Magdalena Cieślik
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Autism Spectrum Disorder
Hippocampus
microglia
medicine.disease_cause
neuroinflammation
lcsh:Chemistry
Pregnancy
Postsynaptic potential
oxidative stress
lcsh:QH301-705.5
Spectroscopy
Valproic Acid
Behavior
Animal
autism spectrum disorders (ASD)
valproic acid (VPA)
Brain
General Medicine
Computer Science Applications
medicine.anatomical_structure
Cerebral cortex
Prenatal Exposure Delayed Effects
Anticonvulsants
Female
lipids (amino acids
peptides
and proteins)
medicine.drug
Offspring
Article
Catalysis
Inorganic Chemistry
medicine
Animals
pre- and postsynaptic proteins
Physical and Theoretical Chemistry
Molecular Biology
Neuroinflammation
Inflammation
business.industry
Organic Chemistry
synaptic ultrastructure
synaptopathology
medicine.disease
Rats
lcsh:Biology (General)
lcsh:QD1-999
Synapses
Autism
business
Neuroscience
Oxidative stress
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 10
International Journal of Molecular Sciences, Vol 21, Iss 3576, p 3576 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21103576
Popis: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions categorized as synaptopathies. Environmental risk factors contribute to ASD aetiology. In particular, prenatal exposure to the anti-epileptic drug valproic acid (VPA) may increase the risk of autism. In the present study, we investigated the effect of prenatal exposure to VPA on the synaptic morphology and expression of key synaptic proteins in the hippocampus and cerebral cortex of young-adult male offspring. To characterize the VPA-induced autism model, behavioural outcomes, microglia-related neuroinflammation, and oxidative stress were analysed. Our data showed that prenatal exposure to VPA impaired communication in neonatal rats, reduced their exploratory activity, and led to anxiety-like and repetitive behaviours in the young-adult animals. VPA-induced pathological alterations in the ultrastructures of synapses accompanied by deregulation of key pre- and postsynaptic structural and functional proteins. Moreover, VPA exposure altered the redox status and expression of proinflammatory genes in a brain region-specific manner. The disruption of synaptic structure and plasticity may be the primary insult responsible for autism-related behaviour in the offspring. The vulnerability of specific synaptic proteins to the epigenetic effects of VPA may highlight the potential mechanisms by which prenatal VPA exposure generates behavioural changes.
Databáze: OpenAIRE
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