title: A high cholesterol diet given to apolipoprotein E-knockout mice has a differential effect on the various neurotrophin systems in the hippocampus.
abstract: Apolipoprotein E (apoE) is one of the major transporters of cholesterol in the body and is essential for maintaining various neural functions in the brain. Given that hypercholesterolemia is a risk factor in Alzheimer's disease (AD), it has been suggested that altered cholesterol metabolism may be involved in the development of the pathogenesis, including neural degeneration, commonly observed in AD patients. Neurotrophic factors and their receptors, which are known to regulate various neural functions, are also known to be altered in various neurodegenerative diseases. We therefore hypothesized that cholesterol metabolism may itself influence the neurotrophin system within the brain. We decided to investigate this possibility by modulating the amount of dietary cholesterol given to apoE-knockout (apoE-KO) and wild-type (WT) mice, and examining the mRNA expression of various neurotrophin ligands and receptors in their hippocampal formations. Groups of eight-week-old apoE-KO and WT mice were fed a diet containing either "high" (HCD) or "normal" (ND) levels of cholesterol for a period of 12 weeks. We found that high dietary cholesterol intake elevated BDNF mRNA expression in both apoE-KO and WT mice and TrkB mRNA expression in apoE-KO animals. On the other hand, NGF and TrkA mRNA levels remained unchanged irrespective of both diet and mouse type. These findings indicate that altered cholesterol metabolism induced by HCD ingestion combined with apoE deficiency can elicit a differential response in the various neurotrophin ligand/receptor systems in the mouse hippocampus. Whether such changes can lead to neural degeneration, and the mechanisms that may be involved in this, awaits further research.
authors.affiliation: Scientific Research Centre, Hebei Medical University Fourth Hospital, Shijiazhuang, Hebei 050011, China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Wang
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Gao
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Warita
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ohta
authors.forename: Shingo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Taira
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Obama
authors.forename: Kuldip S
authors.initials: KS
authors.lastname: Bedi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Bao-En
authors.initials: BE
authors.lastname: Shan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB