title: Ectopic neurogenesis in the forebrain cholinergic system-related areas of a rat dementia model.
abstract: Lesions to the fimbria fornix (FiFx) plus cingulate bundle (CB), the principal routes of communication of forebrain cholinergic regions, produce lasting impairment of spatial learning and memory in mice. We report that extensive neurogenesis takes place in the FiFx, CB, and basalis magnocellularis following FiFx plus CB transection. Immunofluorescence revealed that nestin-expressing cells were present in all 3 areas following lesion; the majority of nestin-positive cells were also positive for 5-bromo-2-deoxy-uridine, a marker of DNA synthesis. Nestin-positive proliferative cells were almost entirely absent from unlesioned tissue. Neurospheres cultured in vitro from lesioned FiFx displayed the characteristics of neural stem cells--proliferation, expression of embryonic markers, and multipotential differentiation into neurons, astrocytes, and oligodendrocytes. At early stages after transection, a small number of immature and migrating doublecortin-immunopositive neurons were detected in lesioned FiFx, where neuronal cell bodies are normally absent. At later stages, postlesion immature neurons developed into β-tubulin III-positive mature neurons. Lentivirus labeling assay implied that the injury-induced neurogenesis in FiFx may be from local neurogenic astrocytes but not from dentate gyrus. These results demonstrate that insult to cholinergic tracts can stimulate neural stem cell proliferation and neuronal regeneration not only in innervated regions but also in the projection pathways themselves. Ectopic neurogenesis in cholinergic system-related areas provides an additional mechanism for repair of cholinergic innervation following damage.
authors.affiliation: Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong City, Jiangsu, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhang
authors.forename: Guohua
authors.initials: G
authors.lastname: Jin
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Linqing
authors.initials: L
authors.lastname: Zou
authors.forename: Jinhong
authors.initials: J
authors.lastname: Shi
authors.forename: Jianbing
authors.initials: J
authors.lastname: Qin
authors.forename: Meiling
authors.initials: M
authors.lastname: Tian
authors.forename: Haoming
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D020532:Basal Nucleus of Meynert; D002454:Cell Differentiation; D049109:Cell Proliferation; D058948:Cell Tracking; D002478:Cells, Cultured; D059329:Cholinergic Neurons; D002828:Choristoma / Q000473:pathology*; D003704:Dementia / Q000473:pathology* / Q000628:therapy; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D020712:Fornix, Brain; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006179:Gyrus Cinguli; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009479:Neuropeptides / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D009479:Neuropeptides; D014404:Tubulin