TY - JOUR
T1 - Protection against developmental retardation in apolipoprotein E- deficient mice by a fatty neuropeptide
T2 - Implications for early treatment of Alzheimer's disease
AU - Gozes, Illana
AU - Bachar, Michal
AU - Bardea, Amos
AU - Davidson, Ariane
AU - Rubinraut, Sarah
AU - Fridkin, Mati
AU - Giladi, Eli
PY - 1997/9
Y1 - 1997/9
N2 - 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.
AB - 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.
KW - Apolipoprorein E
KW - Cholinergic activity
KW - Developmental milestones
KW - Learning and memory
KW - Messenger RNA
KW - Vasoactive intestinal peptide
UR - http://www.scopus.com/inward/record.url?scp=0030752973&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-4695(199709)33:3<329::AID-NEU10>3.0.CO;2-A
DO - 10.1002/(SICI)1097-4695(199709)33:3<329::AID-NEU10>3.0.CO;2-A
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C2 - 9298769
AN - SCOPUS:0030752973
SN - 0022-3034
VL - 33
SP - 329
EP - 342
JO - Journal of Neurobiology
JF - Journal of Neurobiology
IS - 3
ER -