Endurance training upregulates the nitric oxide/soluble guanylyl cyclase/cyclic guanosine 3',5'-monophosphate pathway in the striatum, midbrain and cerebellum of male rats.

The nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) brain pathway plays an important role in motor control. We studied the effects of 6-week endurance training (running) of moderate intensity on this pathway by comparing, between sedentary and endurance-trained young adult male Wistar rats, the expression of endothelial (eNOS) and neuronal (nNOS) NO synthases and of α1, α2 and β1 GC subunits, as well as cGMP levels, in the brain cortex, hippocampus, striatum, midbrain and cerebellum. Additionally, we compared the respective regional expressions of BDNF and the BDNF receptor TrkB. Twenty-four hours after the last training session, the endurance-trained rats showed 3-fold higher spontaneous locomotor activity than their sedentary counterparts in an open-field test. Forty-eight hours after the completion of the training, the trained rats showed significantly elevated BDNF and TrKB mRNAs in the hippocampus, midbrain and striatum, and significantly increased BDNF levels in the hippocampus and striatum. Simultaneously, significant increases were found in mRNA and protein levels and activities of nNOS and eNOS as well as in mRNA and protein levels of GCα2 and GCβ1, but not GCα1, in the striatum, midbrain and cerebellum; no change in these variables was found in the cortex and hippocampus except for marked elevations in cortical GCβ1 mRNA and protein. Changes in regional cGMP levels paralleled those in eNOS, nNOS and GCα2 expression and NOSs' activities. These results suggest that favorable extrapyramidal motor effects of physical training are related to the enhanced activity of the NO/sGC/cGMP pathway in certain motor control-related subcortical brain regions.