Increased Expression of trkB mRNA in Rat Caudate-Putamen Following 6–OHDA Lesions of the Nigrostriatal Pathway

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Abstract

The tyrosine kinase receptors trkB and trkC are essential components of the high-affinity receptors for members of the neurotrophin family, including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Both neurotrophin receptor mRNAs are broadly distributed throughout the caudate-putamen. In animal models of Parkinson's disease, loss of the ventral mesencephalic dopamine projection to the striatum has been shown to alter the expression of several striatal peptides, neurotransmitter-synthesizing enzymes and receptors. To determine if expression of trkB and/or trkC striatal mRNAs is also regulated by the integrity of the dopaminergic afferents, adult rats were given unilateral injections of 6–hydroxydopamine (6–OHDA), selective catecholamine neurotoxin, or vehicle into the right ascending medial forebrain bundle. Following 2 week survival period, in situ hybridization with 35S-labelled cRNA probes for the kinase-specific, full-length form of trkB mRNA and all forms of trkC mRNA was performed in striatal sections. A significant increase in the hybridization density for trkB mRNA was observed in the caudate-putamen ipsilateral to the 6–OHDA injection, compared with the uninjected control side (P < 0.001). In contrast, no alteration in the hybridization density for trkC mRNA was observed in the striatum of 6–OHDA-treated rats. No alterations in trkB or trkC mRNA levels were observed in the striata of vehicle-treated animals. These data suggest that midbrain dopaminergic afferents regulate the expression of trkB mRNA in the caudate-putamen. Alternatively, since dopaminergic neurons of the ventral mesencephalon express BDNF mRNA, the up-regulation of striatal trkB mRNA may reflect compensatory response by striatal neurons due to loss of anterogradely and/or retrogradely derived trophic support from the ventral midbrain.

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