Nitric oxide synthase inhibition during synaptic maturation decreases synapsin I immunoreactivity in rat brain.

During the development of the brain, nitric oxide and synapsins, the latter being phosphoproteins associated to presynaptic membrane vesicles, are abundant in presynaptic terminals and play important and similar roles in neurotransmitter release, morphogenesis, synaptogenesis, and synaptic plasticity. These mechanisms are fundamental for neuronal development and plasticity and constitute important factors for the formation of neuroanatomical structures. Neural nitric oxide synthase (nNOS), synapsin I, and nNOS adapter protein (CAPON) constitute a ternary complex necessary for specific NO and synapsin functions at a presynaptic level. It is not known whether NO absence may affect the presence and/or activity of synapsins during brain development. To understand the role of NO in synaptogenesis, we studied the effects of NOS inhibition on synapsin I expression at a postnatal stage. Rat pups were treated with a competitive NOS antagonist, N-nitro-L-arginine methyl ester, from postnatal days 3 to 23. Control pups received exclusively an equivalent volume of saline solution. Histochemical and immunochemical techniques for NADPH-d and synapsin I, respectively, were carried out. NOS inhibition elicited a significant reduction in synapsin I immunoreactive density and NADPH-d activity in the brain in the analyzed areas-prefrontal cortex, hippocampus, and dorsal thalamus. These data show that the alterations originated by NO and synapsin deficiencies produce a diminution in synaptic density. Thus, functions that depend on the formation of synaptic connections such as learning and memory could be affected by NO deficiency.