Open Access

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

  • Authors:
    • Wensen Pan
    • Shuo Han
    • Lin Kang
    • Sha Li
    • Juan Du
    • Huixian Cui
  • View Affiliations

  • Published online on: June 21, 2016     https://doi.org/10.3892/etm.2016.3470
  • Pages: 1455-1463
  • Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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September-2016
Volume 12 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Pan W, Han S, Kang L, Li S, Du J and Cui H: Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice. Exp Ther Med 12: 1455-1463, 2016.
APA
Pan, W., Han, S., Kang, L., Li, S., Du, J., & Cui, H. (2016). Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice. Experimental and Therapeutic Medicine, 12, 1455-1463. https://doi.org/10.3892/etm.2016.3470
MLA
Pan, W., Han, S., Kang, L., Li, S., Du, J., Cui, H."Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice". Experimental and Therapeutic Medicine 12.3 (2016): 1455-1463.
Chicago
Pan, W., Han, S., Kang, L., Li, S., Du, J., Cui, H."Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1455-1463. https://doi.org/10.3892/etm.2016.3470