Ectopic expression of tropomyosin-related kinase A (TrkA), the high-affinity receptor of nerve growth factor (NGF), has been widely used in cell culture systems to uncover its role in cell survival or death events. In contrast, little is known about the consequences of its expression in vivo. To address this question, adeno-associated virus (AAV) vectors were used to express TrkA in the substantia nigra (SN) and striatum of adult rats. Nine weeks after transfer, tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs were slightly decreased in the ipsilateral SN. This decrease was no longer significant when NGF was delivered into the striatum. There was no change of DAT binding sites or D1 or D2 receptor mRNAs and binding sites in the striatum, suggesting that ectopic TrkA exerts a limited effect on the pool of TH and DAT transcripts, without affecting overall dopamine signaling. When transferred into the striatum, TrkA transgene had no effect on the size of the cholinergic interneurons, but it exerted typical neurotrophic effects, as shown by an enlargement of the projection neurons and nitric oxide synthase (nNOS)-expressing interneurons. This trophic action was amplified by a delivery of NGF. No toxic effect of the transgene was noted. These data indicate that ectopic expression of TrkA may result in the promotion of neurotrophic effects or can influence neuronal plasticity in the absence of exogenous NGF in neuronal populations that naturally fail to respond to this factor.

Changes in the regional distribution of the metabotropic GABA type B receptors (GABA(B)) were investigated in a rat model of Huntington's disease. Animals received a unilateral intrastriatal injection of quinolinic acid (QA), and GABA(B) immunoreactivity was monitored 3, 11, and 21 days postinjection in the striatum and substantia nigra (SN). Two antibodies, recognizing either the GABA(B1) or the GABA(B2) receptor subtypes, were used. QA injection rapidly induced a protracted increase in GABA(B1) or GABA(B2) immunoreactivity in the lesioned striatum, despite the neuronal loss. In the SN, a continuous increase in GABA(B1) and GABA(B2) immunoreactivity was observed at all time points in the ipsilateral pars reticulata (SNr), whereas the pars compacta (SNc) was unaffected by this phenomenon. This increase was supported by a densitometric analysis. At day 21 postlesion induction, intensely labeled stellate cells and processes were found in the ipsilateral SNr, in addition to immunoreactive neurons. Double labeling of GABA(B1) and glial fibrillary acidic protein (GFAP) showed that the stellate cells were reactive astrocytes. Hence, part of the sustained increase in GABA(B) immunoreactivity that takes place in the SNr and possibly the striatum may be ascribed to reactive astrocytes. It is suggested that GABA(B) receptors are up-regulated in these reactive astrocytes and that agonists might influence the extent of this astroglial reaction.