Circadian Dysfunction in a Rotenone-Induced Parkinsonian Rodent Model

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-quinone reductase), has been used to elicit degeneration of dopaminergic neurons and development of parkinsonian syndrome. The present work addresses alterations induced by rotenone on both locomotor and body temperature circadian rhythms in rats. Rotenone-treated rats exhibited abnormalities in equilibrium, postural instability, and involuntary movements. Long-term subcutaneous administration of rotenone significantly reduced mean daily locomotor activity in most animals. During rotenone administration, mean body temperatures (BTs) and BT rhythm amplitudes were significantly lower than those observed in the control group. After long-term rotenone administration, the circadian rhythms of both locomotor activity (LA) and BT displayed decreased amplitudes, lower interdaily phase stability, and higher rhythm fragmentation, as compared to the control rats. The magnitude of the LA and BT circadian rhythm alterations induced by rotenone positively correlated with degree of motor impairment. These results indicate that rotenone induces circadian dysfunction in rats through some of the same mechanisms as those responsible for the development of motor disturbances. (Author correspondence: [email protected])

Keywords:

• Body temperature
• Circadian rhythm
• Locomotor activity
• Parkinson's disease
• Neurodegeneration
• Rat
• Rotenone

ACKNOWLEDGMENTS

This research was supported by grants from the Spanish Ministry of Education and Science (BFU2009-07793/BFI, BFU2010-21945-C02-01, AP2006-04117, and SAF 2007-62262), Instituto de Salud Carlos III (RETICS RD07/0062/0012), ONCE, Fundaluce, and Mutua Madrileña.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.