Hemiparkinsonian rat models: different sensitivity of dopaminergic neurotoxins

Abstract

The pathological hallmark of Parkinson's disease (PD) is a loss of dopamine (DA) neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-pyridinium ion (MPP +) and rotenone are known as DA neurotoxins. However, their neurotoxicities in rat brains in vivo are not fully understood. In this study, we compared the in vivo neurotoxicities of 6-OHDA, MPP + and rotenone using a single intranigral injection. The injection of 6-OHDA caused the greatest loss of DA neurons in both substantia nigra and striatum, and apomorphine induced contralateral rotation. In contrast, apomorphine-induced rotational behavior was in the ipsilateral direction with MPP +, and was not observed with rotenone. Although MPP + and rotenone caused a loss of DA neurons in the substantia nigra, striatal neurodegeneration varied. Thus, intranigral injections of these neurotoxins produce different degrees of DA neurotoxicity in rats in vivo. In addition, the intrastriatal transplantation of human SH-SY5Y cells, DA neuron-like cells, led to the recovery of apomorphine-induced rotational asymmetry in 6-OHDA-lesioned rats. These results suggest that unilateral 6-OHDA-lesioned rats are suitable for evaluating behavioral recovery in studies of the regeneration of differentiated neurons from transplanted neural or embryonic stem (ES) cells.