The effects of intrahippocampal BDNF and NGF on spatial learning in aged long evans rats
- 69 Downloads
Spatial learning rate was compared in cognitively impaired aged rats infused with either brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). BDNF or NGF was infused into the dorsal hippocampus/third ventricle while animals were being trained on the Morris water maze. Training continued until all rats met a spatial learning criterion. Seven weeks later, they were tested for retention of the task, and sacrificed for assessment of hippocampal high-affinity choline uptake (HACU) or hypothalamic biogenic amine levels. NGF, but not BDNF, improved spatial learning rate in aged rats and increased hippocampal choline uptake weeks after withdrawal of NGF. Although BDNF did not improve, spatial learning, it did induce a partial, long-term normalization of the elevated hypothalamic 5-HT levels observed in our aged rats. These data suggest that (1) intrahippocampal/intraventricular infusion of NGF can improve the learning rate of aged, spatial learning-impaired rats, and that this improvement in acquisition could be associated with increased hippocampal cholinergic activity, and (2) that the BDNF-induced normalization of hypothalamic 5-HT levels in aged rats was not sufficient to improve learning rate in aged, spatial learning-impaired rats.
Index EntriesBDNF NGF water maze hippocampus hypothalamus high-affinity choline uptake serotonin cognitive impairment aging spatial learning
Unable to display preview. Download preview PDF.
- Alter C., Boylan C., Fritsche M., Jones B., Jackson C., Wiegand S., Lindsay R., and Hyman C. (1994) Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions.J. Neurochem. 63, 1021–1032.Google Scholar
- Fisher R. A. (1949) The Design of Experiments. Edinburgh: Oliver and Boyd, Ltd.Google Scholar
- Knusel B., Beck K., Winslow J., Rosenthal A., Burton L., Widmer H., Nikolics K., and Hefti F. (1992) Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain.J. Neurosci. 12, 4391–4402.PubMedGoogle Scholar
- Morse J., Wiegand S., Anderson K., You Y., Cai N., Carnahan J., Miller J., DiStefano P., Altar C., Lindsay R., and Alderson R. (1993) Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection.J. Neurosci. 13, 4146–4156.PubMedGoogle Scholar
- Paxinos G and Watson C. (1986)The Rat Brain in Stereotaxic Coordinates. Academic, London.Google Scholar
- Williams L., Cummins V., Welcher A., Cullen M. and Pelleymounter M. (1994) Age-related alterations in trk-B mRNA expression that correlate with memory impairment.Soc. Neurosci Abstract 109, 1.Google Scholar