Glucose Homeostasis Is Not Affected in a Murine Model of Parkinson’s Disease Induced by 6-OHDA

Abstract

There is a mutual relationship between metabolic and neurodegenerative diseases. However, the causal relationship in this crosstalk is unclear and whether Parkinson’s disease (PD) causes a posterior impact on metabolism remains unknown. Considering that, this study aimed to evaluate the appearance of possible changes in metabolic homeostasis due to 6-hydroxydopamine (6-OHDA) administration, a neurotoxin that damage dopaminergic neurons leading to motor impairments that resemble the ones observed in PD. For this, male Wistar rats received bilateral 6-OHDA administration in the dorsolateral striatum, and the motor and metabolic outcomes were assessed at 7, 21, or 35 days post-surgical procedure. Dexamethasone, a diabetogenic glucocorticoid (GC), was intraperitoneally administered in the last 6 days to challenge the metabolism and reveal possible metabolic vulnerabilities caused by 6-OHDA. Controls received only vehicles. The 6-OHDA-treated rats displayed a significant decrease in locomotor activity, exploratory behavior, and motor coordination 7 and 35 days after neurotoxin administration. These motor impairments paralleled with no significant alteration in body mass, food intake, glucose tolerance, insulin sensitivity, and biochemical parameters (plasma insulin, triacylglycerol, and total cholesterol levels) until the end of the experimental protocol on days 35–38 post-6-OHDA administration. Moreover, hepatic glycogen and fat content, as well as the endocrine pancreas mass, were not altered in rats treated with 6-OHDA at the day of euthanasia (38th day after neurotoxin administration). None of the diabetogenic effects caused by dexamethasone were exacerbated in rats previously treated with 6-OHDA. Thus, we conclude that bilateral 6-OHDA administration in the striatum causes motor deficits in rats with no impact on glucose and lipid homeostasis and does not exacerbate the adverse effects caused by excess GC. These observations indicate that neurodegeneration of dopaminergic circuits in the 6-OHDA rats does not affect the metabolic outcomes.

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…Gomes et al (2019) given 20 µg of 6-OHDA in 3 µL (in saline and ascorbic acid) bilaterally into dorsolateral striatum to induce the neurodegeneration in male Wistar rats and assessed the motor and metabolic outcomes on the 7th, 21st, or 35th day after 6-OHDA lesion. The motor abnormalities paralleled without a noteworthy change in body mass, food consumption, glucose tolerance, insulin sensitivity, and other biochemical parameters (such as plasma insulin levels, triacylglycerol, and total cholesterol levels) [ 107 ]. Voronin et al 2019 in their study, administered 5 µg of 6-OHDA in 1 µL (saline and ascorbic acid at 0.5 µL/min) intrastriatal (into right striatum) and evaluated the effect of afobazole (2.5 mg/kg, intraperitoneally) in 6-OHDA-lesioned male CD-1 mice model.…”

Parkinson’s Disease and the Heart: Studying Cardiac Metabolism in the 6-Hydroxydopamine Model

“…When analyzing the impact of 6-OHDA on cholesterol concentrations, a study employing bilateral brain injection found no significant differences in plasma cholesterol levels between parkinsonian rats and control counterparts. Conversely, another study using unilateral 6-OHDA-induced lesion showed reduced concentrations of cholesterol ester in the cerebrospinal fluid of rats [35,36].…”

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“…According to an earlier study, rotenone treatment did not cause an increase in blood glucose 39 . But, treatment with rotenone increased blood glucose in the present study; though the increase was never beyond the 95th centile value for FBS/PBS of Wistar rats (95% upper limit was 6.2 mmol/L and 7.9 mmol/L, respectively) 40 .…”