Differential effects of melatonin on hippocampal neurodegeneration in different aged accelerated senescence prone mouse-8.
OBJECTIVE
A purpose of this study is to compare the differential effects of melatonin on hippocampal neurodegeneration in accelerated senescence prone mouse-8 (SAMP8) which is initiated treatment at different age.


METHODS
The 4-months old SAMP8 mice were injected subcutaneously with melatonin (1 mg/kg/day) for 4 months. Similar treatments were performed in the 7-months old mice. When the animals were complete 11-months old, a series of tests were performed. Y maze test and Eight-arm radial maze task were used to assess cognitive performance. Hippocampal pyramidal cells were estimated by Nissl's staining. By using Gomori's methenamine silver methods, the methenamine silver staining granules (MSSG) were observed in area CA1 of hippocampus. A computer-assisted morphometric study was carried out on the ultrastructure of perikaryal CA1 pyramidal cell mitochondria. The volume density (Vv), surface density (Sv), numerical density (Nv) and mean volume (V) of the mitochondria were calculated.


RESULTS
Melatonin treatment obviously reduced the deposition of MSSG and elevated hippocampal pyramidal cell number while improving the learning and memory deficits of SAMP8. The mice initiated treatment from 4-months old exhibited a greater response to melatonin supplementation than 7-months old mice. It also decreased mean volume (V) and significantly elevated the Sv and Nv of the mitochondria in hippocampal CA1 region. However, 7-months old mice showed little effects on it.


CONCLUSIONS
Our results indicate that the protective effects of melatonin on hippocampal neurodegeneration of SAMP8 are age dependent.
Cheng
Shaowu
S
Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Ma
Chunmei
C
Qu
Huaigang
H
Fan
Wenguo
W
Pang
Jingwen
J
He
Hongwen
H
D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020271:Heredodegenerative Disorders, Nervous System / Q000473:pathology / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008806:Mice, Inbred AKR; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*
D000975:Antioxidants; D008550:Melatonin