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

First Author  Sragovich S Year  2019
Journal  Transl Psychiatry Volume  9
Issue  1 Pages  235
PubMed ID  31534115 Mgi Jnum  J:291937
Mgi Id  MGI:6436058 Doi  10.1038/s41398-019-0569-4
Citation  Sragovich S, et al. (2019) The autism-mutated ADNP plays a key role in stress response. Transl Psychiatry 9(1):235
abstractText  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.
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