Suppressive effects of melatonin on amyloid-beta-induced glial activation in rat hippocampus.
BACKGROUND
Growing evidence indicates that activated glia, as a result of chronic inflammation, are associated with amyloid-beta peptide (Abeta) deposits in the brain of Alzheimer's disease (AD) patients. The purpose of the present study was to investigate, in vivo, the effects of melatonin on glia activation, which may contribute to improved learning and memory in amnesic rats induced by amyloid-beta peptide 25-35 (Abeta25-35).


METHODS
We examined cognitive function using the Morris water maze test. Expression of interleukin 1alpha (IL-1alpha) or complement 1q (C1q) in rat hippocampal tissue was determined by immunohistochemistry.


RESULTS
It was found that Abeta25-35 injected into rat hippocampus induced an impairment in learning and memory and a marked increase of positive glial cells expressing IL-1alpha and C1q in hippocampus, compared with the controls. This suggests that glial activation triggered by Abeta25-35 parallels the dysfunction of learning and memory. Melatonin, at doses of 0.01, 0.1, and 1 mg/kg (i.g. for 10 days), improved learning and memory of rats treated with Abeta25-35. Cells expressing IL-1alpha and C1q were significantly decreased in hippocampus by pretreatment with melatonin at doses of 0.1 mg/kg and 1 mg/kg, but not at the dose of 0.01 mg/kg.


CONCLUSIONS
Our data indicate that melatonin inhibited expressions of proinflammatory factors, which may contribute to improvement of learning and memory function in AD.
Shen
Yuxian
Y
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, P.R. China. shenyuxi@mail.hf.ah.cn
Zhang
Guihong
G
Liu
Lihua
L
Xu
Shuyun
S
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced; D015922:Complement C1q / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D053582:Interleukin-1alpha; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D015922:Complement C1q; D008550:Melatonin