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P3–338: The neurotoxin 2'–NH2–MPTP models degeneration of serotonin axons and alterations in hippocampal BDNF occurring in Alzheimer's disease
Author(s) -
Andrews Anne M.,
Materese Christopher K.,
Szapacs Matthew E.,
Luellen Beth A.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1608
Subject(s) - serotonergic , neurotoxin , serotonin , endocrinology , mptp , medicine , neurotransmitter , dorsal raphe nucleus , locus coeruleus , neuroscience , hippocampal formation , chemistry , hippocampus , norepinephrine , raphe nuclei , basal forebrain , biology , central nervous system , dopamine , receptor , dopaminergic
proteolytic digest and an anti-dementia drug, contains CNTF, GDNF, IGF-1 and IGF-2 peptides. Objective(s): A therapeutic approach to AD is to enhance neurogenic and neurotrophic activities which can compensate the neurodegeneration in this disease. We postulate that the neurotrophic imbalance in AD can be corrected, and neurogenic and neurotrophic activities and, consequently, cognition can be enhanced by treatment with active peptides of neurotrophic factors. Methods: We isolated and propagated adult rat hippocampal neural progenitor cells (AHPs), and treated them with synthetic peptides corresponding to the active regions of CNTF. In a second set of studies we injected (IP) these peptides plus Cerebrolysin or Cerebrolysin alone in normal adult mice, and analyzed their brains for changes in III tubulin and MAP2a,b as early and late neuronal markers, respectively. Results: In studies with AHPs we found that several CNTF peptides increased the levels of III tubulin and MAP2a,b. In mice the number of BrdU positive cells, i.e. dividing cells, increased in the dentate gyrus by 70% in the Cerebrolysin treated and 100% in the Cerebrolysin plus CNTF peptides treated animals. Conclusions: Synthetic peptides corresponding to the active regions of CNTF can increase dentate gyrus neurogenesis. Thus, pharmacological enhancement of neurogenesis by synthetic peptides offers a promising therapeutic approach to AD and related neurodegenerative disorders.