Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders

Bryers, Amelia and Hawkes, Cheryl A and Parkin, Edward and Dawson, Neil (2024) Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders. Biochemical Society Transactions. ISSN 0300-5127

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Abstract

Autism spectrum disorders (ASD) are a heterogenous set of syndromes characterised by social impairment and cognitive symptoms. Currently, there are limited treatment options available to help people with ASD manage their symptoms. Understanding the biological mechanisms that result in ASD diagnosis and symptomatology is an essential step in developing new interventional strategies. Human genetic studies have identified common gene variants of small effect and rare risk genes and copy number variants (CNVs) that substantially increase the risk of developing ASD. Reverse translational studies using rodent models based on these genetic variants provide new insight into the biological basis of ASD. Here we review recent findings from three ASD associated CNV mouse models (16p11.2, 2p16.3 and 22q11.2 deletion) that show behavioural and cognitive phenotypes relevant to ASD. These models have identified disturbed excitation-inhibition neurotransmitter balance, evidenced by dysfunctional glutamate and GABA signalling, as a key aetiological mechanism. These models also provide emerging evidence for serotoninergic neurotransmitter system dysfunction, although more work is needed to clarify the nature of this. At the brain network level, prefrontal cortex (PFC) dysfunctional connectivity is also evident across these models, supporting disturbed PFC function as a key nexus in ASD aetiology. Overall, published data highlight the utility and valuable insight gained into ASD aetiology from preclinical CNV mouse models. These have identified key aetiological mechanisms that represent putative novel therapeutic targets for the treatment of ASD symptoms, making them useful translational models for future drug discovery, development and validation. [Abstract copyright: © 2024 The Author(s).]

Item Type:
Journal Article
Journal or Publication Title:
Biochemical Society Transactions
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1303
Subjects:
?? neurodevelopmental disordersserotoningabamouse modelsglutamateneuroimagingbiochemistry ??
ID Code:
224238
Deposited By:
Deposited On:
26 Sep 2024 13:50
Refereed?:
Yes
Published?:
Published
Last Modified:
26 Sep 2024 13:50