Decreased neurogenesis after cholinergic forebrain lesion in the adult rat

Cooper-Kuhn, Christiana M. and Winkler, Jürgen and Kuhn, H. Georg (2004) Decreased neurogenesis after cholinergic forebrain lesion in the adult rat. JOURNAL OF NEUROSCIENCE RESEARCH, 77 (2). pp. 155-165. ISSN 0360-4012, 1097-4547

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Abstract

Adult neurogenesis has been shown to be regulated by a multitude of extracellular cues, including hormones, growth factors, and neurotransmitters. The cholinergic system of the basal forebrain is one of the key transmitter systems for learning and memory. Because adult neurogenesis has been implicated in cognitive performance, the present work aims at defining the role of cholinergic input for adult neurogenesis by using an immunotoxic lesion approach. The immunotoxin 192IgG-saporin was infused into the lateral ventricle of adult rats to selectively lesion cholinergic neurons of the cholinergic basal forebrain (CBF), which project to the two main regions of adult neurogenesis: the dentate gyrus and the olfactory bulb. Five weeks after lesioning, neurogenesis, defined by the number of cells colocalized for bromodeoxyuridine (BrdU) and the neuronal nuclei marker NeuN, declined significantly in the granule cell layers of the dentate gyrus and olfactory bulb. Furthermore, immunotoxic lesions to the CBF led to increased numbers of apoptotic cells specifically in,the subgranular zone, the progenitor region of the dentate gyrus, and within the periglomerular layer of the olfactory bulb. We propose that the cholinergic system plays a survival-promoting role for neuronal progenitors and immature neurons within regions of adult neurogenesis, similar to effects observed previously during brain development. As a working hypothesis, neuronal loss within the CBF system leads not only to cognitive deficits but may also alter on a cellular level the functionality of the dentate gyrus, which in turn may aggravate cognitive deficits. (C) 2004 Wiley-Liss, Inc.

Item Type: Article
Uncontrolled Keywords: AMINO-ACID NEUROTRANSMITTERS; ROSTRAL MIGRATORY STREAM; OLFACTORY-BULB CULTURES; NEWLY GENERATED NEURONS; NERVE GROWTH-FACTOR; LONG-TERM SURVIVAL; NEURAL STEM-CELLS; 192 IGG-SAPORIN; BASAL FOREBRAIN; DENTATE GYRUS; dentate gyrus; olfactory bulb; immunotoxin; cell death; progenitor cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Petra Gürster
Date Deposited: 18 Jan 2022 10:38
Last Modified: 18 Jan 2022 10:38
URI: https://pred.uni-regensburg.de/id/eprint/37437

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