Changes in brain cholinergic markers and spatial learning in old galanin-overexpressing mice

Brain Res. 2007 Mar 23;1138:10-20. doi: 10.1016/j.brainres.2006.12.069. Epub 2006 Dec 29.


The cholinergic forebrain system is involved in learning and memory, and its age-dependent decline correlates with a decrease in cognitive performance. Since the neuropeptide galanin participates in cholinergic neuron regulation, we have studied 19- to 23-month-old male mice overexpressing galanin under the platelet-derived growth factor B promoter (GalOE) and wild-type (WT) littermates by monitoring behavioral, neurochemical and morphological/histochemical parameters. In the Morris water maze test, old transgenic animals showed a significant impairment in escape latency in the hidden platform test compared to age-matched WT animals. The morphological/histochemical studies revealed that cholinergic neurons in the basal forebrain display a slight, age- but not genotype-related, alteration in choline acetyltransferase- (ChAT) immunoreactivity. The neurochemical studies showed an age-related decline in ChAT activity in the cerebral cortex of all mice, whereas in the hippocampal formation this effect was seen in GalOE but not WT animals. Expression of BDNF mRNA in the hippocampal formation, as evaluated by RT-PCR, was reduced in old animals; no age- or genotype-induced variations in NGF mRNA expression were observed. These data suggest that galanin overexpression further accentuates the age-related decline of the cholinergic system activity in male mice, resulting in impairment of water maze performance in old animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / psychology*
  • Animals
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / genetics
  • Cerebral Cortex / enzymology
  • Choline O-Acetyltransferase / metabolism*
  • Galanin / genetics
  • Galanin / metabolism*
  • Hippocampus / enzymology
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Male
  • Maze Learning / physiology*
  • Mice
  • Mice, Transgenic
  • Motor Activity / physiology
  • Nerve Growth Factors / genetics
  • Prosencephalon / cytology
  • Prosencephalon / enzymology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swimming


  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • RNA, Messenger
  • Galanin
  • Choline O-Acetyltransferase