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Keywords = synaptopathology

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21 pages, 1011 KiB  
Review
Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder
by Iris W. Riemersma, Robbert Havekes and Martien J. H. Kas
Genes 2022, 13(1), 28; https://doi.org/10.3390/genes13010028 - 23 Dec 2021
Cited by 7 | Viewed by 5289
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is [...] Read more.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy. Full article
(This article belongs to the Special Issue From Genes to Therapy in Autism Spectrum Disorder)
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33 pages, 7463 KiB  
Article
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
by Magdalena Gąssowska-Dobrowolska, Magdalena Cieślik, Grzegorz Arkadiusz Czapski, Henryk Jęśko, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Agnieszka Dominiak, Rafał Polowy, Robert Kuba Filipkowski, Lidia Babiec and Agata Adamczyk
Int. J. Mol. Sci. 2020, 21(10), 3576; https://doi.org/10.3390/ijms21103576 - 18 May 2020
Cited by 47 | Viewed by 7320
Abstract
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 [...] Read more.
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. Full article
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