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.

Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats

“…Circadian rhythm disruption is a major non-motor symptom in PD patients (Schapira et al 2017; Willison et al 2013). In ROT-induced PD rat model, circadian rhythms were disrupted (Lax et al 2012). Circadian rhythms are controlled and maintained by a series of clock genes (Mohawk et al 2012; Buhr and Takahashi 2013; Partch et al 2014).…”

A New Perspective for Parkinson’s Disease: Circadian Rhythm

“…Chronic rotenone-treated rats also showed lower amplitudes and instability phase of body temperature, as compared to the controls. The magnitude of the alterations was positively correlated with the degree of movement disorders [51].…”

Immunocal® and Preservation of Glutathione as a Novel Neuroprotective Strategy for Degenerative Disorders of the Nervous System

“…More specifically, oxidative damage within the *Address correspondence to this author at the University of Denver, Department of Biological Sciences, 2199 S. University Blvd., Denver, CO, 80208; Tel: (303)-871-5654; Fax: (303)-871-3471: E-mail: daniel.linseman@du.edu mitochondria may target complex I of the ETC and further increase ROS production, as is observed in PD [8]. Pathophysiologically relevant complex I inhibitors such as rotenone and N-methylpyridinium ion (MPP + ), generate free radicals and induce disease progression characteristic of PD which is modeled in vitro and in vivo for studies of potential therapeutics [9,10]. Methods aimed at bolstering endogenous antioxidant defense mechanisms to enhance scavenging of free radicals generated during disease progression hold therapeutic potential for neurodegenerative diseases such as PD.…”