Protection against developmental retardation in apolipoprotein E- deficient mice by a fatty neuropeptide: Implications for early treatment of Alzheimer's disease

Illana Gozes*, Michal Bachar, Amos Bardea, Ariane Davidson, Sarah Rubinraut, Mati Fridkin, Eli Giladi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Stearyl-Nle17-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, mice deficient in apolipoprotein E (ApoE), a molecule associated with the etiology of Alzheimer's disease, served as a model to investigate the developmental and protective effects of SNV. In comparison to control animals, the deficient mice exhibited (a) reduced amounts of VIP messenger RNA; (b) decreased cholinergic activity (c) significant retardation in the acquisition of developmental milestones: forelimb placing behavior and cliff avoidance behavior; and (d) learning and memory impairments. Daily injections of SNV to ApoE-deficient newborn pups resulted in increased cholinergic activity and marked improvements in the time of acquisition of behavioral milestones, with peptide-treated animals developing as fast as control animals and exhibiting improved cognitive functions after cessation of peptide treatment. Specificity was demonstrated in that treatment with a related peptide (PACAP), pituitary adenylate cyclase-activating peptide, produced only limited amelioration. As certain genotypes of ApoE increase the probability of Alzheimer's disease, early counseling and preventive treatments may now offer an important route for therapeutics design.

Original languageEnglish
Pages (from-to)329-342
Number of pages14
JournalJournal of Neurobiology
Volume33
Issue number3
DOIs
StatePublished - Sep 1997

Keywords

  • Apolipoprorein E
  • Cholinergic activity
  • Developmental milestones
  • Learning and memory
  • Messenger RNA
  • Vasoactive intestinal peptide

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