Chronic and progressive dopaminergic neuronal death in substantia nigra associates with a decrease in serum levels of glucose and free fatty acids, the role of interlokin-1 beta.

Abstract

Human studies indicate that Parkinson's disease (PD) associates with disruption in metabolism of glucose and free fatty acids (FFA). Studies have shown that interlukin-1beta (IL-1β) causes hypoglycemia through insulin- independent mechanisms. Here, we investigated association between dopaminergic neuronal death, as the main pathophysiological mechanism underlying PD, and serum levels of glucose, FFA and IL-1β in 6-hydroxydopamine (6-OHDA) animal model of PD. Neurotoxin of 6-OHDA was injected into medial forebrain bundle and multiple behavioral testes were carried out during eight weeks thereafter. Blood was collected before the toxin and in second and eight weeks thereafter. Then, brain of the animals was perfused to assess survival of dopaminergic (DAergic) neurons in substantia nigra by tyrosine hydroxylase (TH) immunohistochemistry. Glucose, FFA and IL-1β levels were determined using calorimetric method and specific ELISA kits. In compare to control, 6-OHDA- treated rats had less glucose and FFA levels in the eight week and higher IL-1β level in the both second and eight weeks. Based on severity of behavioral symptoms, 6-OHDA- treated rats were divided into two subgroups of severe and mild. Number of TH- positive cells in these subgroups was 83 and 45% less than that in control. Also, both subgroups showed less weight gain, lower glucose and FFA and higher IL-1β in eight week. Our data indicate that moderate to severe progressive DAergic neuronal death in substantia nigra associates with a decrease in serum levels of glucose and FFA. Increase in IL-1β production following neuronal death possibly mediated this decrease.