Numan S, Seroogy K B
Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536, USA.
Eur J Neurosci. 1997 Mar;9(3):489-95. doi: 10.1111/j.1460-9568.1997.tb01626.x.
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.
酪氨酸激酶受体trkB和trkC是神经营养因子家族成员（包括脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3））高亲和力受体的重要组成部分。两种神经营养因子受体mRNA广泛分布于整个尾状核-壳核。在帕金森病动物模型中，已证明腹侧中脑多巴胺向纹状体的投射丧失会改变几种纹状体肽、神经递质合成酶和受体的表达。为了确定trkB和/或trkC纹状体mRNA的表达是否也受多巴胺能传入神经完整性的调节，给成年大鼠右侧内侧前脑束上行支单侧注射6-羟基多巴胺（6-OHDA，一种选择性儿茶酚胺神经毒素）或溶剂。在2周的存活期后，在纹状体切片中用35S标记的cRNA探针进行原位杂交，检测激酶特异性全长形式的trkB mRNA和所有形式的trkC mRNA。与未注射的对照侧相比，在6-OHDA注射同侧的尾状核-壳核中观察到trkB mRNA杂交密度显著增加（P < 0.001）。相反，在6-OHDA处理大鼠的纹状体中未观察到trkC mRNA杂交密度的改变。在溶剂处理动物的纹状体中未观察到trkB或trkC mRNA水平的改变。这些数据表明中脑多巴胺能传入神经调节尾状核-壳核中trkB mRNA的表达。另外，由于腹侧中脑的多巴胺能神经元表达BDNF mRNA，纹状体trkB mRNA的上调可能反映了纹状体神经元由于腹侧中脑顺行和/或逆行衍生的营养支持丧失而产生的代偿反应。
