Choline pivaloyl ester enhances brain expression of both nerve growth factor and high-affinity receptor TrkA, and reverses memory and cognitive deficits, in rats with excitotoxic lesion of nucleus basalis magnocellularis.
The aim of present work was the evaluation of the effects on brain levels of nerve growth factor (NGF) and of its high-affinity tyrosine kinase A receptor (TrkA), induced in rats unilaterally lesioned at nucleus basalis magnocellularis (NBM), by treatment with choline pivaloyl ester (CPE). CPE was daily administered (60 micromol/Kg ip) during 3 weeks to rats selectively lesioned by AMPA infusion into right NBM; the intact left NBM serving as control. NGF levels were determined in cerebral cortex and hippocampus by Elisa assay. TrkA receptor expression was evaluated in right NBM by Western blotting analysis. CPE treatment significantly increased NGF levels in both hippocampus and neocortex in right NBM, compared with intact left counter-part and controls. Western blotting showed an evident enhancement in TrkA receptor expression in lesioned right NBM in comparison with intact left counter-part and controls. CPE treatment was also able to restore, in bilaterally NBM-lesioned rats, the disrupted cortical EEG and HVS activities as well as to reverse deficits in learning and memory in spatial navigation and probe trials, and cognitive capacities in object recognition task.
Rispoli
Vincenzo
V
Department of Pharmacobiological Sciences, University Magna Graecia of Catanzaro, Complesso Ninì Barbieri, Roccelletta di Borgia, Italy. rispoli@unicz.it
Marra
Rosario
R
Costa
Nicola
N
Rotiroti
Domenicantonio
D
Tirassa
Paola
P
Scipione
Luigi
L
De Vita
Daniela
D
Liberatore
Felice
F
Carelli
Vincenzo
V
D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003517:Cyclopentanes / Q000627:therapeutic use*; D004569:Electroencephalography; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009483:Neuropsychological Tests; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D003517:Cyclopentanes; C449399:cyclopentenone carboxylic acid; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA