In:
Molecular Brain, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2021-12)
Abstract:
Autophagy is a lysosomal degradation pathway that regulates cellular homeostasis. It is constitutively active in neurons and controls the essential steps of neuronal development, leading to its dysfunction in neurodevelopmental disorders. Although mTOR-associated impaired autophagy has previously been reported in neurodevelopmental disorders, there is lack of information about the dysregulation of mTOR-independent autophagy in neurodevelopmental disorders. In this study, we investigated whether the loss of Epac2, involved in the mTOR-independent pathway, affects autophagy activity and whether the activity of autophagy is associated with social–behavioral phenotypes in mice with Epac2 deficiencies . We observed an accumulation of autophagosomes and a significant increase in autophagic flux in Epac2-deficient neurons, which had no effect on mTOR activity. Next, we examined whether an increase in autophagic activity contributed to the social behavior exhibited in Epac2 −/− mice. The social recognition deficit observed in Epac2 −/− mice recovered in double transgenic Epac2 −/− : Atg5 + /− mice. Our study suggests that excessive autophagy due to Epac2 deficiencies may contribute to social recognition defects through an mTOR-independent pathway.
Type of Medium:
Online Resource
ISSN:
1756-6606
DOI:
10.1186/s13041-021-00814-6
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2436057-0
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