Acetylcholine-secreting cells improve age-induced memory deficits

Dickinson-Anson, Heather and Winkler, Juergen and Fisher, Lisa J. and Song, Hong-Jun and Poo, Mu-ming and Gage, Fred H. (2003) Acetylcholine-secreting cells improve age-induced memory deficits. MOLECULAR THERAPY, 8 (1). pp. 51-61. ISSN 1525-0016

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Abstract

The present study examined whether aged rats with naturally occurring cognitive deficits in spatial learning and memory would benefit from local chronic supplementation of acetylcholine. Aged impaired and aged unimpaired rats were pretested in the water maze to characterize the extent of age-induced cognitive impairment. Groups were matched for extent of deficits. The animals subsequently received implants of either acetylcholine-releasing cells or control cells into the cortical and hippocampal target regions of the basal forebrain. One week postgrafting, spatial learning and memory were retested using the same behavioral procedure. All aged groups acquired the platform position more slowly than young controls. However, aged impaired rats grafted with acetylcholine-releasing cells performed significantly better than aged impaired rats with control grafts, and they did not differ from aged unimpaired groups. A spatial memory probe test revealed that memory for the escape platform location of the acetylcholine-grafted rats was significantly better than that of rats with control grafts and matched the performance of young controls. In vitro, biochemical and electrophysiological analyses of the engineered cells confirmed choline acetyltransferase activity and showed quantal release of acetylcholine from the transduced cells. In vivo, RT-PCR of microdissected grafts indicated that the engineered cells expressed the choline acetyltransferase transgene for up to 40 days postgrafting. These results indicate that locally restricted supplementation of acetylcholine into the two major target regions of the cholinergic basal forebrain of aged impaired rats ameliorates some age-related cognitive deficits.

Item Type: Article
Uncontrolled Keywords: NERVE GROWTH-FACTOR; INTRAHIPPOCAMPAL SEPTAL GRAFTS; CHOLINERGIC NEURON ATROPHY; SPATIAL RECENT MEMORY; ALZHEIMERS-DISEASE; BASAL FOREBRAIN; LEARNING IMPAIRMENTS; RATS; ACETYLTRANSFERASE; NGF; acetylcholine; choline acetyltransferase; aging; basal forebrain; nucleus basalis; medial septum; neocortex; hippocampus; learning; memory; water maze; engineered cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Sep 2021 09:42
Last Modified: 08 Sep 2021 09:42
URI: https://pred.uni-regensburg.de/id/eprint/38872

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