Locus Coeruleus Is Involved in Weight Loss in a Rat Model of Parkinson's Disease: An Effect Reversed by Deep Brain Stimulation

Abstract

IntroductionIn Parkinson's disease (PD) weight loss is a secondary phenomenon to the progressive neurodegeneration that changes after deep brain stimulation of the subthalamic nucleus (DBS-STN) leading to increased weight gain. The mechanism responsible for this profile in weight variation may be secondary to a central metabolic control influenced by the noradrenergic system. In this study authors evaluate the effect of additional noradrenergic neuronal degeneration, namely of the locus coeruleus (LC), on weight variation in the 6-hydroxydopamine (6-OHDA) rat model of PD. Material and methodsAn experimental group of parkinsonian animals with additional 6-OHDA lesion of the LC was developed to analyze the effect of this lesion on the metabolic state of rats before and after DBS-STN. Rats were placed in metabolic cages for evaluation of weight, food and liquid intake and urine and fecal volume, before and after DBS-STN. The effects of 6-OHDA lesions and DBS-STN on motor behavior were also monitored. Tissue levels of monoamines in the striatum of 6-OHDA-lesioned animals and catecholamine levels in urine and plasma were evaluated. ResultsIn the experimental group of Parkinsonian animals with 6-OHDA degeneration of the striatum alone, no effects on weight gain, food intake and other metabolic parameters were observed before or after DBS-STN. Additional lesion of the LC produced a significant decrease in weight gain with a trend toward a decrease in solid intake. Chronic DBS-STN in rats with LC and striatum degeneration abolished the weight loss without producing changes to food intake and other metabolic parameters. Additional degeneration of the LC was not accompanied by significant changes in motor behavior but produced an additional decrease in striate monoamines levels namely a decrease in the DA/l-DOPA ratio. ConclusionsIn PD degeneration of noradrenergic neurons, in particular of the LC, may be required to observe side effects unrelated to motor symptoms such as body weight deregulation. Our results support the notion that the LC may be important in maintaining the activity of the nigrostriatal dopamine pathways, and thus play a crucial role in weight variation in a PD.