title: Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a severe neuroinflammatory disease. CD4(+)Foxp3(+) regulatory T cells (Tregs) modulate various inflammatory diseases via suppressing Th cell activation. There are increasing evidences that Tregs have beneficial roles in neurodegenerative diseases. Previously, we found the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro.
  
  
  METHODS
  To examine the effects of bvPLA2 on AD, bvPLA2 was administered to 3xTg-AD mice, mouse model of Alzheimer's disease. The levels of amyloid beta (Aβ) deposits in the hippocampus, glucose metabolism in the brain, microglia activation, and CD4(+) T cell infiltration were analyzed to evaluate the neuroprotective effect of bvPLA2.
  
  
  RESULTS
  bvPLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of Aβ deposits in the hippocampus were dramatically decreased by bvPLA2 treatment. This neuroprotective effect of bvPLA2 was associated with microglial deactivation and reduction in CD4(+) T cell infiltration. Interestingly, the neuroprotective effects of bvPLA2 were abolished in Treg-depleted mice.
  
  
  CONCLUSIONS
  The present studies strongly suggest that the increase of Treg population by bvPLA2 treatment might inhibit progression of AD in the 3xTg AD mice.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. jh486ms22@naver.com.
authors.forename: Minsook
authors.initials: M
authors.lastname: Ye
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), 70, Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. hschung@kiom.re.kr.
authors.forename: Hwan-Suck
authors.initials: HS
authors.lastname: Chung
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. lcj8078@naver.com.
authors.forename: Chanju
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. anstlr72@hanmail.net.
authors.forename: Moon Sik
authors.initials: MS
authors.lastname: Yoon
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, University of Science and Technology, #215-4 Gongneug-dong, Nowon-ku, Seoul, 139-241, Republic of Korea. yar11@hanmail.net.
authors.forename: A Ram
authors.initials: AR
authors.lastname: Yu
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, University of Science and Technology, #215-4 Gongneug-dong, Nowon-ku, Seoul, 139-241, Republic of Korea. kjs@kirams.re.kr.
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, College of Korean Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. soulhus@khu.ac.kr.
authors.forename: Deok-Sang
authors.initials: DS
authors.lastname: Hwang
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. ishim@khu.ac.kr.
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea. hbae@khu.ac.kr.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001514:Bee Venoms / Q000737:chemistry; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D054467:Phospholipases A2 / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000235:genetics; D011877:Radionuclide Imaging; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D001514:Bee Venoms; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D054467:Phospholipases A2