Mutual regulation between the intercellular messengers nitric oxide and brain-derived neurotrophic factor in rodent neocortical neurons

The diffusible factors, nitric oxide (NO) and brain-derived neurotrophic fa ctor (BDNF) are both suggested to be intercellular messengers that have sim ilar synaptic activities and developmental influences in the brain. In the present study, we have analysed their mutual regulation with respect to the ir production in rodent neocortical neurons. Some of the cultured rat neoco rtical neurons exhibited immunoreactivity for both neuronal NO synthase (NO S) and the BDNF receptor trkB. Neuronal NOS appeared to be activated autono mously and produced NO in culture as monitored by nitrite accumulation. Inh ibition of the endogenous NO production in culture by a NOS inhibitor, N-G- monomethyl-L-arginine (NMMA), enhanced basal expression of BDNF mRNA and pr otein. Similarly, cerebroventricular administration of another NOS inhibito r, N-omega-nitro-L-arginine methylester (L-NAME), but not D-NAME or saline, increased BDNF content in the neocortex. In the opposite direction, howeve r, BDNF appeared to function as a positive regulator for NO synthesis. Addi tion of BDNF upregulated the neuronal NOS expression as well as NO producti on in neocortical culture. In agreement, BDNF knock-out mice exhibited sign ificant impairment of neuronal NOS expression in the neocortex. Taken toget her, these observations suggest that the trans-synaptic signalling molecule s, NO and BDNF, influence the production of each other and mutually regulat e the strength of their intercellular communications.