Nitric oxide-induced cGMP synthesis in the cholinergic system during the development and aging of the rat brain.

ABSTRACT

cGMP synthesis in cholinergic neurons of the basal forebrain, the caudate putamen, and the tegmento-pedunculopontine nucleus of the rat was studied during development after birth at P1, P4, P10, and P21, in the adult, and during aging. NO-mediated cGMP synthesis in these neurons was studied using the approach of in vitro incubation of brain slices in combination with cGMP-immunocytochemistry. The percentage of NO-responsive, cGMP-synthesizing cholinergic cells in the septum and diagonal band of Broca decreased from 75% to 6% in adult animals and to 2% in aged ones. In the caudate putamen, this decrease was from 81% to 21% in adult and 11% in aged animals. Cholinergic cells of the tegmento-pedunculopontine nucleus were unresponsive to NO and never showed cGMP-immunoreactivity. In addition, it was observed that the amount of NO-responsive, cGMP-synthesizing cholinergic fibers in the hippocampus declined in parallel with the maturation of the septal-hippocampal cholinergic pathway, whereas in the caudate putamen, this colocalization became complete 2 weeks after birth. It is concluded that the property of NO-mediated cGMP synthesis in the cholinergic nuclei of the forebrain is developmentally regulated after birth and that NO-cGMP signal transduction has a role in establishing cholinergic neuronal connections in the hippocampus and caudate putamen.