Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Several toxin-induced animals models simulate the motor deficits occurring in PD. Among them, the unilateral 6-hydroxydopamine (6-OHDA) model is frequently used in rats and has the advantage of presenting side-biased motor impairments. However, the behavioral consequences of a unilateral 6-OHDA-lesion have, so far, not been described in detail in mice. The aim of this study was to characterize mice with unilateral 6-OHDA-lesions placed in the median forebrain bundle using several motor behavioral tests in order to identify the most suitable predictor of nigral cell loss. Mice underwent various drug-induced (amphetamine- and apomorphine-induced rotation) and spontaneous motor tests (cylinder, rotarod, elevated body swing, and stride length test). The amphetamine-induced rotation test, the cylinder and the rotarod test were most sensitive and reliable in detecting loss of tyrosine hydroxylase-immunoreactive cells in the substantia nigra. This study demonstrates that substantial and stable unilateral 6-OHDA-induced lesions can be established in mice, and that these lesions can be functionally assessed using several different side-bias-based behavioral tests. This mouse model offers the opportunity to use transgenic mouse strains and study the interactions between genes of interest and toxins in relation to Parkinson's disease etiology in the future.

Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

“…ATP6V0C plays a central role in H + transport as one part of the multi-subunit complex of ATPase [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. Israel and his group initially proposed that medatophore forms a proteinaceous pore by the six transmemebrane c subunits of ATPase [10,11].…”

Motor deficits and altered striatal gene expression in aphakia (ak) mice

“…Rotarod-The rotarod apparatus (Accurotor, Accuscan Instruments, Columbus, OH, USA) provides a sensitive means to measure deficits of motor coordination resulting from defects of the dopaminergic system (Baquet et al, 2004;Fetsko et al, 2005;Fowler et al, 2002;Iancu et al, 2005). Each mouse (n= ak -60, wt -54) was given three trials over 3 days on an accelerating protocol (0-40 rpm in 80 seconds).…”

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

“…Nevertheless, the use of 6-OHDA in this set-up is of general interest as it is becoming the preferred neurotoxin to create mice models of Parkinson's disease compared to the widely used MPTP. Several reasons to avoid the use of MPTP are proposed, including its strain-, age-and gender-dependency in mice (Alvarez-Fischer et al, 2008;Grealish et al, 2010;Iancu et al, 2005). For this reason, the in vivo salicylate trapping technique was adapted to investigate compounds for their scavenging activity on 6-OHDA-induced ROS formation in the mouse striatum.…”

“…Therefore, we administered the same amount of 6-OHDA as the one used for striatal lesioning of mice, in the absence of salicylate. This approach allowed to make a correlation between the acute effects of 6-OHDA and its long-term effects previously described (Alvarez-Fischer et al, 2008;Grealish et al, 2010;Iancu et al, 2005), such as nigral degeneration and reduced striatal DA content.…”