Galanin expression within the basal forebrain in Alzheimer's disease: Comments on therapeutic potential

Elliott J. Mufson, Ulrika Kahl, Robert Bowser, Deborah C. Mash, Jeffrey H. Kordower, Darlene C. Deecher

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The inhibitory neuropeptide galanin has widespread distribution throughout the central nervous system. Studies indicate that galanin modulates cognition by regulating cholinergic basal forebrain (CBF) neuron function. The chemoanatomic organization of galanin within the mammalian CBF differs across species. In monkeys, all CBF neurons coexpress galanin, whereas in apes and humans galanin is found within a separate population of interneurons that are in close apposition to the CBF perikarya. Pharmacologic investigations revealed a low and high affinity galanin receptor within the basal forebrain in humans. In vitro autoradiographic investigations of the primate brain indicate that galanin receptors are concentrated within the anterior subfields of the CBF as well as the bed nucleus of the stria terminalis, amygdala, and entorhinal cortex. Galaninergic fibers hyperinnervate remaining CBF neurons in Alzheimer's disease. Because galanin inhibits the release of acetylcholine in the hippocampus, it has been suggested that the overexpression of galanin in Alzheimer's disease may downregulate the production of acetylcholine within CBF perikarya, further exacerbating cholinergic cellular dysfunction in this disorder. These observations suggest that the development of a potent galanin antagonist would be a useful step towards the successful pharmacologic treatment of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)291-304
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume863
DOIs
StatePublished - Jan 1 1998

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this