Preliminary exploration of the role and mechanism of BAIAP2 in learning and memory impairment in ADHD.

Abstract

Attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder affecting children, presents with core symptoms of inattention, hyperactivity, and impulsivity, along with frequent comorbid learning and memory dysfunction. Emerging evidence implicates hippocampal dysfunction in ADHD-related learning and memory deficits, with brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) emerging as a critical molecular player. While BAIAP2 has been independently associated with synaptic plasticity and ADHD pathogenesis, its specific role in ADHD-associated learning and memory impairment remains unexplored. Using spontaneously hypertensive rats (SHR), we demonstrated significantly reduced hippocampal BAIAP2 expression compared to controls. Notably, methylphenidate (MPH) treatment increased BAIAP2 levels, while targeted BAIAP2 overexpression rescued learning and memory deficits, as evidenced by Morris water maze (MWM) performance. Furthermore, we preliminarily explored the possible regulatory interactions between BAIAP2 and the long non-coding RNA lncNONRATT002035.2. These findings establish BAIAP2 as a pivotal mediator of hippocampal-dependent learning and memory dysfunction in ADHD and uncovered new aspects of disease pathology and potential targets for therapy.The newly discovered lncNONRATT002035.2-BAIAP2 axis warrants further investigation to elucidate its pathophysiological significance.