PMID- 25858697
OWN - NLM
STAT- MEDLINE
DCOM- 20160509
LR  - 20161125
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 59
IP  - 1
DP  - 2015 Aug
TI  - Melatonin ameliorates amyloid beta-induced memory deficits, tau 
      hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3beta pathway in the mouse 
      hippocampus.
PG  - 47-59
LID - 10.1111/jpi.12238 [doi]
AB  - Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative 
      disease, pathologically characterized by the accumulation of amyloid beta (Abeta) 
      aggregation in the brain, and is considered to be the primary cause of cognitive 
      dysfunction. Abeta aggregates lead to synaptic disorder, tau hyperphosphorylation, 
      and neurodegeneration. In this study, the underlying neuroprotective mechanism of 
      melatonin against Abeta1-42-induced neurotoxicity was investigated in the mice 
      hippocampus. Intracerebroventricular (i.c.v.) Abeta1-42-injection triggered memory 
      impairment, synaptic disorder, hyperphosphorylation of tau protein, and 
      neurodegeneration in the mice hippocampus. After 24 hr of Abeta1-42 injection, the 
      mice were treated with melatonin (10 mg/kg, intraperitonially) for 3 wks, 
      reversed the Abeta1-42-induced synaptic disorder via increasing the level of 
      presyanptic (Synaptophysin and SNAP-25) and postsynaptic protein [PSD95, p-GluR1 
      (Ser845), SNAP23, and p-CREB (Ser133)], respectively, and attenuated the 
      Abeta1-42-induced memory impairment. Chronic melatonin treatment attenuated the 
      hyperphosphorylation of tau protein via PI3K/Akt/GSK3beta signaling by activating 
      the p-PI3K, p-Akt (Ser 473) and p-GSK3beta (Ser9) in the Abeta1-42-treated mice. 
      Furthermore, melatonin decreased Abeta1-42 -induced apoptosis through decreasing the 
      overexpression of caspase-9, caspase-3, and PARP-1 level. Additionally, the 
      evaluation of immunohistochemical analysis of caspase-3, Fluorojade-B, and Nissl 
      staining indicated that melatonin prevented neurodegeneration in Abeta1-42-treated 
      mice. Our results demonstrated that melatonin has neuroprotective effect against 
      Abeta1-42-induced neurotoxicity through decreasing memory impairment, synaptic 
      disorder, tau hyperphosphorylation, and neurodegeneration via PI3K/Akt/GSK3beta 
      signaling in the Abeta1-42-treated mouse model of AD. On the basis of these results, 
      we suggest that melatonin could be an effective, promising, and safe 
      neuroprotective candidate for the treatment of progressive neurodegenerative 
      disorders, such as AD.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Ali, Tahir
AU  - Ali T
AD  - Department of Biology and Applied Life Science (BK 21), College of Natural 
      Sciences (RINS), Gyeongsang National University, Jinju, Korea.
FAU - Kim, Myeong Ok
AU  - Kim MO
AD  - Department of Biology and Applied Life Science (BK 21), College of Natural 
      Sciences (RINS), Gyeongsang National University, Jinju, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (tau Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Glycogen Synthase Kinase 3/genetics/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - Melatonin/*therapeutic use
MH  - Memory Disorders/chemically induced/*drug therapy/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurodegenerative Diseases/*drug therapy/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Phosphorylation/drug effects
MH  - tau Proteins/*metabolism
OTO - NOTNLM
OT  - Abeta1-42
OT  - PI3/Akt/GSK3beta signaling
OT  - Tau hyperphosphorylation
OT  - melatonin
OT  - neurodegeneration
OT  - synaptic disorder
EDAT- 2015/04/11 06:00
MHDA- 2016/05/10 06:00
CRDT- 2015/04/11 06:00
PHST- 2015/03/19 00:00 [received]
PHST- 2015/04/03 00:00 [accepted]
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2016/05/10 06:00 [medline]
AID - 10.1111/jpi.12238 [doi]
PST - ppublish
SO  - J Pineal Res. 2015 Aug;59(1):47-59. doi: 10.1111/jpi.12238. Epub 2015 May 12.