Daily rhythms of serotonin metabolism and the expression of clock genes in suprachiasmatic nucleus of rotenone-induced Parkinson's disease male Wistar rat model and effect of melatonin administration.

Abstract

The circadian system in suprachiasmatic nucleus (SCN) involves regulated serotonin levels and coordinated expression of various clock genes. To understand circadian disfunction in the age-related neurodegenerative disorder Parkinson's disease (PD), the rotenone-induced PD (RIPD) male Wistar rat model was used. The alterations in the rhythmic dynamic equilibrium of interactions between the various components of serotonin metabolism and the molecular clock were measured. There was significant decrease in the mean 24 h levels of tryptophan, 5-hydroxytryptophan (5-HTP), serotonin (5-HT), N-acetyl serotonin (NAS) and melatonin (MEL) by approximately 63, 51, 76 and 96% respectively ( p ≤ 0.05). However significant increase in 5-methoxy indole acetic acid (5-MIAA), 5-methoxy tryptophol (5-MTOH), 5-hydroxy tryptophol (5-HTOH) indicated increased serotonin catabolism with the abolition of daily rhythms of MEL, 5-HTP and 5-MIAA in RIPD. 24 h mean levels of rPer1, rCry1, rBmal1 reduced by about 0.5, 0.74 and 0.39-fold and increased for rPer2 by about 1.7-fold. The daily pulse of rPer2, rCry1, rCry2 and rBmal1 significantly decreased by 0.36, 0.6, 0.14, 0.1 and 0.2-fold. As melatonin, an antioxidant and an endogenous synchronizer of rhythm declined in RIPD male Wistar rat model, the effects of melatonin-administration on the rhythmic expression of various clock genes were studied. Interestingly, melatonin-administration resulted in restoration of the phase of rPer1 daily rhythm in RIPD indicating differential sensitivity of various clock components towards melatonin. The animals which were administered both rotenone and MEL for 48 days interestingly showed neuroprotective effects in dark phase on correlations between expression of various genes.