Effect of the weaver mutation on the expression of dopamine membrane transporter, tyrosine hydroxylase and vesicular monoamine transporter in dopaminergic neurons of the substantia nigra and the ventral tegmental area

Abstract

The adult homozygous weaver mutant mouse ( wv/ wv) is characterized by a loss of dopamine (DA) neurons in the nigrostriatal pathway. Quantitative in situ hybridization of three different dopaminergic markers: dopamine membrane transporter (DAT), tyrosine hydroxylase (TH), and vesicular monoamine transporter (VMAT2) was performed on individual dopaminergic cells of the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) in 2-month-old wv/ wv mice, in order to investigate the metabolic state of remaining dopaminergic cell bodies and gain further insight into modifications observed on dopaminergic nerve terminals in the striatum and the nucleus accumbens. Cellular expression of DAT mRNA in remaining dopaminergic cells of both the SNC and the VTA was decreased in the wv/ wv mice compared to the wild-type mice ( +/ +). In contrast, the expression of TH and VMAT2 mRNA remained unchanged in the wv/ wv mice. Furthermore, in 7-day-old wv/ wv mice, before the onset of cell death in the midbrain, DAT mRNA levels were reduced in dopaminergic neurons in both the SNC and VTA. In these animals, the cellular expression of TH mRNA remained unchanged. These results taken together indicate that DAT expression is one of the first targets in the ventral mesencephalon of the wv mutation, inducing a specific decrease of DA uptake in the striatum and the nucleus accumbens. The alteration of the DA membrane transporter could play a role in the progression of DA neuronal death in the wv mice.