Heterozygous Cc2d1a mice show sex-dependent changes in the Beclin-1/p62 ratio with impaired prefrontal cortex and hippocampal autophagy

Sener, Elif Funda, Dana, Halime, Tahtasakal, Reyhan, Hamurcu, Zuhal, Taheri, Serpil, Delibasi, Nesrin, Mehmetbeyoglu, Ecmel, Sukranli, Zeynep Yilmaz, Dal, Fatma, Tufan, Esra, Oflamaz, Asli Okan, Doganyigit, Zuleyha, Ozkul, Yusuf and Rassoulzadegan, Minoo 2023. Heterozygous Cc2d1a mice show sex-dependent changes in the Beclin-1/p62 ratio with impaired prefrontal cortex and hippocampal autophagy. Progress in Neuro-Psychopharmacology and Biological Psychiatry 125 , 110764. 10.1016/j.pnpbp.2023.110764

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Abstract

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders characterized by repetitive behaviors, lack of social interaction and communication. CC2D1A is identified in patients as an autism risk gene. Recently, we suggested that heterozygous Cc2d1a mice exhibit impaired autophagy in the hippocampus. We now report the analysis of autophagy markers (Lc3, Beclin and p62) in different regions hippocampus, prefrontal cortex, hypothalamus and cerebellum, with an overall decrease in autophagy and changes in Beclin-1/p62 ratio in the hippocampus. We observed sex-dependent variations in transcripts and protein expression levels. Moreover, our analyses suggest that alterations in autophagy initiated in Cc2d1a heterozygous parents are variably transmitted to offspring, even when the offspring's genotype is wild type. Aberration in the autophagy mechanism may indirectly contribute to induce synapse alteration in the ASD brain.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0278-5846
Date of First Compliant Deposit:	30 June 2023
Date of Acceptance:	6 April 2023
Last Modified:	14 Nov 2023 21:43
URI:	https://orca.cardiff.ac.uk/id/eprint/160751

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