Neurogenesis in Neurotoxin-induced Animal Models for Parkinson's Disease-A Review of the Current Status

Abstract

Animal models for Parkinson's disease (PD) are essential for understanding its pathogenesis and for development and testing of new therapies. Discoveries of endogenous neurogenesis in the adult mammalian brain give new insight into the cell-based approach for treatment of neurodegenerative disorders, such as PD. Although a great deal of interest has been focused on endogenous neurogenesis in neurotoxin-induced animal models for PD, it still remains controversial whether neural stem cells migrate into the injured area and contribute to repopulation of depleted dopaminergic neurons in neurotoxin-injured adult brains. The purpose of this review is to examine the data available regarding neurogenesis in neurotoxin-induced animal models of PD. It is hoped that data from the animal investigations available in the literature will promote understanding of the neurotoxin-induced animal models for PD.

Keywords: 6-OHDA; MPTP; Parkinson’s disease; animal model; neurogenesis.

Fig. 1.

MPTP is a byproduct during the chemical synthesis of a meperidine analog. MPTP neurotoxicity develops only after metabolization to MPDP+ by MAO-B in glial cells and then to MPP+, the active toxic compound.

Fig. 2.

Schematic representations of the migratory pattern of newly generated A cells in the SVZ (up) and the cell populations in the SGZ of the DG (bottom left) and SVZ (bottom right) in the adult rodent brain (adapted from Ref. 24).

Fig. 3.

MPTP reduces the number of BrdU+ cells in the SVZ and OB. The majority of BrdU-positive cells in the SVZ are rapidly depleted at 2 days, and only few BrdU-positive cells migrate into the OB at 7 days after MPTP administration.