title: Alterations in cognitive function in prepubertal mice with protein malnutrition: relationship to changes in choline acetyltransferase.
abstract: We have found that protein malnutrition (PM) causes a significant impairment of memory-related behavior on the 15th and 20th day after the start of PM (5% casein) feeding in prepubertal mice but not in postpubertal mice, as measured by a passive-avoidance task. This impairment was almost completely reversed by merely switching to a standard protein (20% casein) diet on the 10th day after the start of PM. However, the reversal was not observed when the switching to a standard protein regimen was done on the 15th day of the PM diet. Interestingly, the impairment of memory-related behavior on the 20th day was improved by the chronic administration of physostigmine (0.1 mg/kg/day x last 10 days, i.p.), a cholinesterase inhibitor. To correlate brain cholinergic neuron function with the memory-related behavior impairment induced by PM, microphotometry was used to determine the histological distribution of the imunofluorescence intensity for choline acetyltransferase (ChAT), a functional marker of presynapse in cholinergic neurons. The change in the intensity of fluorescence indicated that ChAT protein was decreased in the hippocampus (CA1, CA3 and dentate gyrus) on the 20th day after PM feeding in comparison with controls. These results suggest the possibility that the memory-related behavior deficits observed in prepubertal mice with PM are caused by a dysfunction of the cholinergic neurons in the hippocampus.
authors.affiliation: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. osamun@tohoku-pharm-ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawasai
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Yamadera
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.forename: Ryoo
authors.initials: R
authors.lastname: Taniguchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Hiraga
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mawatari
authors.forename: Fukie
authors.initials: F
authors.lastname: Niijima
authors.forename: Koichi
authors.initials: K
authors.lastname: Tan-No
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tadano
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D010830:Physostigmine / Q000494:pharmacology; D011488:Protein Deficiency / Q000150:complications*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D002795:Choline O-Acetyltransferase