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Exp Ther Med. 2016 Sep;12(3):1455-1463. Epub 2016 Jun 21.

Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice.

Author information

1
Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China; Department of Respiration Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
2
Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
3
Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China; Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Shijiazhuang, Hebei 050031, P.R. China.

Abstract

The current study focused on how dihydrotestosterone (DHT) regulates synaptic plasticity in the hippocampus of mild cognitive impairment male senescence-accelerated mouse prone 8 (SAMP8) mice. Five-month-old SAMP8 mice were divided into the control, castrated and castrated-DHT groups, in which the mice were castrated and treated with physiological doses of DHT for a period of 2 months. To determine the regulatory mechanisms of DHT in the cognitive capacity, the effects of DHT on the morphology of the synapse and the expression of synaptic marker proteins in the hippocampus were investigated using immunohistochemistry, qPCR and western blot analysis. The results showed that the expression of cAMP-response element binding protein (CREB), postsynaptic density protein 95 (PSD95), synaptophysin (SYN) and developmentally regulated brain protein (Drebrin) was reduced in the castrated group compared to the control group. However, DHT promoted the expression of CREB, PSD95, SYN and Drebrin in the hippocampus of the castrated-DHT group. Thus, androgen depletion impaired the synaptic plasticity in the hippocampus of SAMP8 and accelerated the development of Alzheimer's disease (AD)-like neuropathology, suggesting that a similar mechanism may underlie the increased risk for AD in men with low testosterone. In addition, DHT regulated synaptic plasticity in the hippocampus of mild cognitive impairment (MCI) SAMP8 mice and delayed the progression of disease to Alzheimer's dementia. In conclusion, androgen-based hormone therapy is a potentially useful strategy for preventing the progression of MCI in aging men. Androgens enhance synaptic markers (SYN, PSD95, and Drebrin), activate CREB, modulate the fundamental biology of synaptic structure, and lead to the structural changes of plasticity in the hippocampus, all of which result in improved cognitive function.

KEYWORDS:

Alzheimer's disease; aging; cognition disorders; dihydrotestosterone; mice; mild

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