The protective effect and potential mechanism of NRXN1 on learning and memory in ADHD rat models

Exp Neurol. 2021 Jul 3:113806. doi: 10.1016/j.expneurol.2021.113806. Online ahead of print.ABSTRACTThe learning and memory network is highly complex and remains unclear. The hippocampus is the location of learning and memory function. Impairment of synaptic morphology and synaptic plasticity (i.e., long-term potentiation) appears to cause learning and memory deficits. Several studies have indicated the role of NRXN1 in regulating the synaptic function, but little is known on its role in learning and memory dysfunction associated with attention deficit and hyperactivity disorder (ADHD). Our results showed that overexpression and interference of NRXN1 in vivo, respectively, affected learning and memory, as was assessed by Morris water maze tests, in spontaneously hypertensive rats (SHRs) and Sprague Dawley (SD) rats. We found that SD rats performed better after methylphenidate (MPH) treatment in salvage trials. Accordingly, the change of NRXN1 led to altered synapse-related gene (PSD95, SYN1, GAP43, NLGN1) expression, further providing evidence of its role in the maintenance of synaptic plasticity. We also verified that the expression of synapse-related genes synchronously changed with NRXN1expression in the behavioral assessment. The expression of NRXN1 was confirmed to affect the expression of synapse-related genes after its interference and overexpression in the primary hippocampal neurons in vitro. These results confirmed our hypothesis that NRXN1 might nucleate an overall ...
Source: Experimental Neurology - Category: Neurology Authors: Source Type: research