Effects of treadmill running on brain activation and the corticotropin-releasing hormone system

The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-FOS was also determined in the three conditions of this study. The levels of c-FOS mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-FOS mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington's nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-FOS mRNA that is widely distributed throughout the brain. c-FOS mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-FOS mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c-FOS mRNA distribution, that treadmill running has a strong stress component.