Increased expression of trkB mRNA in rat caudate--putamen following 6-OHDA lesions of the nigrostriatal pathway.
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), a selective catecholamine neurotoxin, or vehicle into the right ascending medial forebrain bundle. Following a 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 a compensatory response by striatal neurons due to a loss of anterogradely and/or retrogradely derived trophic support from the ventral midbrain.
Numan
S
S
Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536, USA.
Seroogy
K B
KB
D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism*; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D015513:Oncogene Proteins / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology*; D011699:Putamen / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014793:Visual Cortex / Q000187:drug effects
D015513:Oncogene Proteins; D012333:RNA, Messenger; C065400:oncogene protein trk; D016627:Oxidopamine