The autism-mutated ADNP plays a key role in stress response

Shlomo Sragovich, Yarden Ziv, Sharon Vaisvaser, Noam Shomron, Talma Hendler, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Activity-dependent neuroprotective protein (ADNP), discovered and first characterized in our laboratory (IG), is vital for mammalian brain formation and presents one of the leading genes mutated de novo causing an autistic syndrome, namely the ADNP syndrome. Furthermore, a unique mouse model of Adnp-haploinsufficiency was developed in the laboratory (IG), with mice exhibiting cognitive and social deficiencies. ADNP is regulated by vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP). In this respect, PACAP was independently identified as a sexual divergent master regulator of the stress response. Here, we sought to determine the impact of the Adnp genotype and the efficacy of PACAP pre-treatment when subjecting Adnp+/− mice to stressful conditions. Significant sex differences were observed with Adnp+/− males being more susceptible to stress in the object and social recognition tests, and the females more susceptible in the open field and elevated plus maze tests. Splenic Adnp expression and plasma cortisol levels in mice were correlated with cognition (male mice) and anxiety-related behavior. These findings were further translated to humans, with observed correlations between ADNP expression and stress/cortisol content in a young men cohort. Altogether, our current results may establish ADNP as a marker of stress response.

Original languageEnglish
Article number235
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

Funding

FundersFunder number
AMN Foundation
Israel Ministry of Science and Technology
Naomi Foundation
Fundación Alicia Koplowitz
Canadian Friends of Tel Aviv University
Eldee FoundationISF 1424/14
Tel Aviv University

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