Protective effect of recombinant human somatotropin on amyloid beta-peptide induced learning and memory deficits in mice.
This study aimed to examine the effects of the recombinant human somatotropin (rhGH) on protecting neuronal function, and improving learning and memory deficits in mice. Mice were intracerebroventricularly (icv) injected with the aggregated amyloid beta-peptide (Abeta) to mimic the Alzheimer's disease (AD). The learning and memory functions in mice were examined by the step through test (an index of long-term memory) and the water maze performance (an index of spatial recognition memory). The results indicated that the mice treated with rhGH showed significant reduction of the error counts and the long memory retentions in the step-through test, and short swimming times in the water maze performance. Toxic effects of free radicals, damages of cholinergic neurons, and increased lipid peroxidation appeared in the cerebra of Abeta-treated mice, manifesting an increase of malondialdehyde (MDA) and decline of glutathione (GSH) level, an increment of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities, and a reduction of the acetylcholine (ACh) level. The gel electrophoresis pattern of the cerebra of mice treated with Abeta showed a typical DNA ladder of apoptosis. The in vivo experiments showed that the rhGH treatment significantly reversed the elevated MDA, ChAT, AChE, and the decreased GSH, ACh levels in the Abeta model mice. The results suggested that there were potential uses of the neuroprotective action of rhGH in the remedy of AD.
Ling
Fu Ai
FA
Department of Biochemistry and Pharmacology, Institute of Pharmacology and Toxicology, Beijing 100850, China.
Hui
Dong Zhao
DZ
Ji
Sun Man
SM
D000544:Alzheimer Disease / Q000139:chemically induced / Q000517:prevention & control; D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D010446:Peptide Fragments; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019382:Human Growth Hormone