A role for TrkA during maturation of striatal and basal forebrain cholinergic neurons in vivo.
نویسندگان
چکیده
Nerve growth factor (NGF), acting via the TrkA receptor, has been shown to regulate the survival and maturation of specific neurons of the peripheral nervous system. Furthermore, exogenous NGF has potent actions on TrkA-expressing cholinergic neurons of the basal forebrain (BFCNs) and striatum. However, initial analysis of mice lacking NGF or TrkA revealed that forebrain cholinergic neurons were present in these animals through the fourth postnatal week. Because of the potential effects of NGF/TrkA interactions on these developing neurons, we have analyzed quantitatively the striatal and basal forebrain cholinergic neurons in trkA knock-out mice. By postnatal day (P) 7/8, forebrain cholinergic neurons are smaller in trkA (-/-) mice than those in wild-type littermate controls. However, cholinergic neuron number and fiber density in the hippocampus, a target region of BFCNs, are grossly intact. Interestingly, by P20-P25 trkA knock-outs contain significantly fewer (20-36%) and smaller cholinergic neurons in both the striatum and septal regions, as compared with controls. Cholinergic fiber density within the hippocampus also is depleted in knock-outs by the end of the second postnatal week. Contrary to some predictions, despite expression of p75(NTR) in the absence of trkA in BFCNs of these knock-out mice, many cells, although smaller, are still alive at P25. Our data suggest that, in the absence of NGF/TrkA signaling, striatal cholinergic neurons and BFCNs do not mature fully and that BFCNs begin to atrophy and/or die surrounding the time of target innervation.
منابع مشابه
Regulation of TrkA and ChAT expression in developing rat basal forebrain: evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons.
TrkA is a receptor tyrosine kinase whose activation transduces NGF signaling. TrkA expression has been demonstrated in NGF-responsive adult basal forebrain cholinergic neurons (BFCNs). Several lines of evidence have suggested that endogenous NGF plays a role in the development and differentiation of these neurons. We examined TrkA expression during development. TrkA mRNA and protein were presen...
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Emerging evidence suggests that the p75 neurotrophin receptor (p75NTR) mediates cell death; however, it is not known whether p75NTR negatively regulates other neuronal phenotypes. We found that mice null for p75NTR displayed highly significant increases in the size of basal forebrain cholinergic neurons, including those that are TrkA-positive. Cholinergic hippocampal target innervation also was...
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ورودعنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 17 20 شماره
صفحات -
تاریخ انتشار 1997