The 6-Hydroxydopamine model of parkinson’s disease

Abstract

The neurotoxin 6-hydroxydopamine (6-OHDA) continues to constitute a valuable topical tool used chiefly in modeling Parkinson's disease in the rat. The classical method of intracerebral infusion of 6-OHDA involving a massive destruction of nigrostriatal dopaminergic neurons, is largely used to investigate motor and biochemical dysfunctions in Parkinson's disease. Subsequently, more subtle models of partial dopaminergic degeneration have been developed with the aim of revealing finer motor deficits. The present review will examine the main features of 6-OHDA models, namely the mechanisms of neurotoxin-induced neurodegeneration as well as several behavioural deficits and motor dysfunctions, including the priming model, modeled by this means. An overview of the most recent morphological and biochemical findings obtained with the 6-OHDA model will also be provided, particular attention being focused on the newly investigated intracellular mechanisms at the striatal level (e.g., A(2A) and NMDA receptors, PKA, CaMKII, ERK kinases, as well as immediate early genes, GAD67 and peptides). Thanks to studies performed in the 6-OHDA model, all these mechanisms have now been hypothesised to represent the site of pathological dysfunction at cellular level in Parkinson's disease.

Effect of Sesamol in Association With Folic Acid on 6-Ohda Induced Parkinsonian Animals- Biochemical, Neurochemical and Histopathological Evidence

“…This kind of effect proves that the 6-hydroxydopamine toxication is the ideal animal model for PD studies [25,26]. The levels of glucose, triglycerides, and protein were estimated, and we found significant alteration between the control, lesion and treated group.…”

Proprioceptive deficits in Parkinson's disease: From clinical data to animal experimentation.

“…When neuron deterioration reaches such levels, compensation mechanisms are insufficient to contain deficits, leading to the manifestation of initial PD motor symptoms (Simola, Morelli, & Carta, 2007).…”

“…The primary adopted techniques include genetic manipulation and, more frequently, neurotoxininduced dopamine depletion (Meredith et al, 2008;Simola et al, 2007).…”

Mitochondrial proteomics as a selective tool for unraveling Parkinson’s disease pathogenesis

“…Animal models, based on the toxic damage induced by the neurotoxin 6-hydroxydopamine (6-OHDA) are used extensively for accurately mimicking aspects of human PD in rats [13]. Although the precise mechanism underlying 6-OHDA-induced area-specific neuronal damage occurs remains to be ascertained, studies making use of the 6-OHDA rat model have shown repeatedly that this involves mitochondrial functional impairment [14]. For instance, 6-OHDA has been shown to generate iron-dependent oxidative stress and deplete antioxidant (e.g., glutathione) levels, while it was also reported that 6-OHDA inhibits complexes I and IV of the mitochondrial electron transport chain (METC) [15,16].…”