The effects of intrahippocampal BDNF and NGF on spatial learning in aged Long Evans rats.
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.
Pelleymounter
M A
MA
Amgen, Inc., Thousand Oaks, CA 91320, USA.
Cullen
M J
MJ
Baker
M B
MB
Gollub
M
M
Wellman
C
C
D000375:Aging / Q000523:psychology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002794:Choline / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D007263:Infusions, Parenteral; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013028:Space Perception
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012701:Serotonin; D002794:Choline