Ahnak in the prefrontal cortex mediates behavioral correlates of stress resilience and rapid antidepressant action in mice.
Frontiers in molecular neuroscience January 1, 2024 Dionnet L Bhatti, Junghee Jin, Jia Cheng et al. 4 citations
Ahnak protein in the prefrontal cortex (PFC) is elevated in mice that are resilient to chronic social stress, and its levels correlate with social interaction after stress. Deleting Ahnak from PFC or forebrain glutamatergic neurons makes mice more susceptible to stress, indicating Ahnak is needed for resilience. Ketamine and its metabolite (2R,6R)-hydroxynorketamine increase Ahnak expression in the PFC. Removing Ahnak from forebrain glutamatergic neurons blocks the restorative behavioral effects of ketamine or HNK in stress-susceptible mice and reduces excitatory synaptic activity in layer II/III pyramidal neurons. Ahnak in glutamatergic PFC neurons may be critical for behavioral resilience and the antidepressant actions of ketamine or HNK.