|Göteborgs universitets publikationer
Decreased neurogenesis after cholinergic forebrain lesion in the adult rat.
Författare och institution:
Christiana M Cooper-Kuhn (Institutionen för klinisk neurovetenskap); Jürgen Winkler (-); Hans-Georg Kuhn (Institutionen för klinisk neurovetenskap)
Journal of neuroscience research, 77 ( 2 ) s. 155-65
Artikel, refereegranskad vetenskaplig
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
Acetylcholine, metabolism, Animals, Antibodies, Monoclonal, Apoptosis, physiology, Basal Nucleus of Meynert, injuries, physiopathology, Brain Injuries, physiopathology, Cell Differentiation, physiology, Cell Division, physiology, Cholinergic Fibers, physiology, ultrastructure, Cognition Disorders, pathology, physiopathology, Dentate Gyrus, cytology, growth & development, Down-Regulation, physiology, Immunotoxins, Male, N-Glycosyl Hydrolases, Nerve Regeneration, physiology, Neural Pathways, injuries, physiopathology, Neuronal Plasticity, physiology, Olfactory Bulb, cytology, growth & development, Rats, Rats, Inbred F344, Ribosome Inactivating Proteins, Type 1, Stem Cells, cytology, physiology