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

View Article: PubMed Central - PubMed

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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Quantitative polymerase chain reaction showing effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice, showing gene expression of SYN, PSD95, Drebrin, and CREB in the Castration, DHT and P8 groups. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, post synaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.
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f3-etm-0-0-3470: Quantitative polymerase chain reaction showing effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice, showing gene expression of SYN, PSD95, Drebrin, and CREB in the Castration, DHT and P8 groups. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, post synaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.

Mentions: The mRNA expression of creb, psd95, syn and drebrin in hippocampal neurons in different groups was similar to that of their protein expression levels (Fig. 3). The creb, psd95, syn and drebrin mRNAs levels in the castration group were the lowest (0.597±0.075, 0.853±0.079, 0.420±0.057 and 0.328±0.019, respectively) and were significantly decreased compared with the P8 group (1.245±0.059, P<0.01; 1.231±0.116, P<0.01; 0.894±0.052, P<0.01; 0.452±0.041, P<0.01, respectively) and the DHT group (1.177±0.101, P<0.01; 1.194±0.064, P<0.01; 0.861±0.026, P<0.01; 0.422±0.018, P<0.01, respectively) (Table IV, Fig. 3).


Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice
Quantitative polymerase chain reaction showing effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice, showing gene expression of SYN, PSD95, Drebrin, and CREB in the Castration, DHT and P8 groups. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, post synaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997989&req=5

f3-etm-0-0-3470: Quantitative polymerase chain reaction showing effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice, showing gene expression of SYN, PSD95, Drebrin, and CREB in the Castration, DHT and P8 groups. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, post synaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.
Mentions: The mRNA expression of creb, psd95, syn and drebrin in hippocampal neurons in different groups was similar to that of their protein expression levels (Fig. 3). The creb, psd95, syn and drebrin mRNAs levels in the castration group were the lowest (0.597±0.075, 0.853±0.079, 0.420±0.057 and 0.328±0.019, respectively) and were significantly decreased compared with the P8 group (1.245±0.059, P<0.01; 1.231±0.116, P<0.01; 0.894±0.052, P<0.01; 0.452±0.041, P<0.01, respectively) and the DHT group (1.177±0.101, P<0.01; 1.194±0.064, P<0.01; 0.861±0.026, P<0.01; 0.422±0.018, P<0.01, respectively) (Table IV, Fig. 3).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus