L-DOPA reverses motor deficits associated with normal aging in mice

Abstract

We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling.

Fig. 1

L-DOPA treatment reverses age-related deficits in motor coordination. A) Old animals made significantly more errors than their younger counterparts when traversing the challenge beam (* p<0.05; n = 9-12 in saline groups). L-DOPA significantly reduced the errors made by old animals (**p< 0.05; n = 6 in L-DOPA groups) such that the number of errors was similar to that in the young animals. B) Young and old animals made similar numbers of rears in the cylinder test. Although there is a trend for a decrease in rears in the old animals, this was not significant. Furthermore, L-DOPA had no effect on the number of rears in either young or old animals.

Fig. 2

Striatal DA and DA metabolite levels did not change with age or L-DOPA administration Moreover, the ratio of DOPAC and/or HVA to DA was unaltered with age or L-DOPA treatment indicating no change in DA turnover. (data not shown)

Fig. 3

Phenotypic markers of DA neurons are unaltered with age and L-DOPA treatment. A) Striatal DAT expression was not changed with age or L-DOPA administration. B) The expression of TH, the rate limiting enzyme in DA synthesis, was not changed with age or L-DOPA administration.