The controversy about spinal neuronal nitric oxide synthase: under which conditions is it up- or downregulated?

In recent years, the regulation of the synthesis of nitric oxide (NO) in th e central nervous system has attracted much interest because it has been sh own that NO is in volved in a wide variety of functions such as neuroprotec tion, neurotoxicity, neurotransmission, and neuroplasticity under physiolog ical and pathophysiological conditions. However, the use of different detec tion techniques for neuronal nitric oxide synthase (nNOS), different animal species, and different experimental lesions has led to contradictory resul ts concerning the direction of changes in spinal nNOS expression. This pape r summarizes the available data on the expression on nNOS in the spinal cor d under physiological and pathological conditions and tries to extract some of the basic mechanisms that underlie neuronal up- or downregulation of th is enzyme. Wherever possible, results obtained with the NADPH-dependent dia phorase reaction are also included for reasons of comparison. The main conc lusion is that changes in spinal nNOS expression critically depend on the t ype of afferent fibres activated by a specific lesion as well as the intens ity and duration of input to the spinal cord. This input may be further mod ified by supraspinal influences. Thus the exact composition of these factor s, which is undoubtfully highly variable between different experimental mod els, appears to determine whether the spinal NO system responds with an up- or downregulation of nNOS expression or in a bidirectional way. With regar d to the diaphorase reaction it is becoming increasingly clear that under p athological conditions data obtained with this reaction differ markedly fro m those obtained with immunohistochemical visualization of nNOS.