Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.

Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S-nitrosylation of gephyrin (SNO-gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO-gephyrin is significantly increased in the BLA of high-anxiety rats and a downregulation of SNO-gephyrin at cysteines 212 and 284 produced anxiolytic effect.

Gephyrin Palmitoylation in Basolateral Amygdala Mediates the Anxiolytic Action of Benzodiazepine.

Background: Benzodiazepines (BZDs) have been used to treat anxiety disorders for more than five decades as the allosteric modulator of the gamma-aminobutyric acid A receptor (GABAR). Little is known about other mechanisms of BZDs. Here, we describe how the rapid stabilization of postsynaptic GABAR is essential and sufficient for the anxiolytic effect of BZDs via a palmitoylation-dependent mechanism.

De-palmitoylation by N-(tert-Butyl) hydroxylamine inhibits AMPAR-mediated synaptic transmission via affecting receptor distribution in postsynaptic densities.

Aims: Palmitoylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) subunits or their "scaffold" proteins produce opposite effects on AMPAR surface delivery. Considering AMPARs have long been identified as suitable drug targets for central nervous system (CNS) disorders, targeting palmitoylation signaling to regulate AMPAR function emerges as a novel therapeutic strategy. However, until now, much less is known about the effect of palmitoylation-deficient state on AMPAR function.