Differential maturational patterns of nitric oxide synthase-I and NADPH diaphorase in functionally distinct cortical areas of the mouse cerebral cortex

Abstract

 Nitric oxide (NO) regulates several functions both in the developing and the adult central nervous systems (CNS). During development, NO is assumed to contribute to the histogenetic differentiation of the CNS especially through the modulation of programmed neuronal death. The embryonal and postnatal changes in the distribution of the cortical NO producing system were studied in Balb/c mice using immunocytochemistry for nitric oxide synthase-I (NOS-I) and NADPH-diaphorase (NADPH-d) enzyme histochemistry. NOS-I reactive neurons (RN) appeared first at embryonic day 14 (E14) in the spinal cord in the vicinity of the central canal, and later, at E16–18, in the thalamus and striatum. The first cortical region to present NOS-I reactivity was the parietal cortex, which happened at E18–20. After E20 the number of NOS-I RN increased in every cortical area, plateauing at postnatal day 4 (P4). In parietal regions, however, the highest density of NOS-I RN was observed already at P1. The neuronal packing density (PD) of NOS-I RN declined until adulthood, interrupted by a transient increase in some cortical areas at the onset of puberty. The heterochronous appearance of NOS-I during pre- and postnatal development of different brain regions and the sequence of up- and downregulation of expression until adult stages points to an important role of NO in brain development and functional differentiation.