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

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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.

No MeSH data available.


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Western blotting showing the effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice. Western blot detected SYN, PSD95, Drebrin and CREB protein expression in the (A) castration, DHT and P8 groups. A statistical graph showing the difference of protein expression in the (B) four groups. The results are presented as the mean ± standard deviation (n=5). Statistical analysis was performed using one-way ANOVA with LSD post-hoc test. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, postsynaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.
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f2-etm-0-0-3470: Western blotting showing the effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice. Western blot detected SYN, PSD95, Drebrin and CREB protein expression in the (A) castration, DHT and P8 groups. A statistical graph showing the difference of protein expression in the (B) four groups. The results are presented as the mean ± standard deviation (n=5). Statistical analysis was performed using one-way ANOVA with LSD post-hoc test. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, postsynaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.

Mentions: The protein bands for CREB in hippocampus were clearly visible in the different groups (Fig. 2). The integrated OD (IOD) value of CREB in the castration group was 0.589±0.075, which was significantly lower compared to the P8 group at 1.113±0.152 (P<0.01). However, the IOD value for CREB in the DHT group was 1.032±0.118, which was significantly different compared to the castration group (P<0.01). The expression levels of SYN (0.453±0.074, 0.947±0.117, 0.891±0.126), PSD95 (0.109±0.007, 0.193±0.018, 0.205±0.025), and Drebrin (0.189±0.045, 0.632±0.058, 0.613±0.092) was consistent with that of CREB protein. There was a statistically significant difference (P<0.01) between the castration group and P8 groups (Table III).


Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice
Western blotting showing the effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice. Western blot detected SYN, PSD95, Drebrin and CREB protein expression in the (A) castration, DHT and P8 groups. A statistical graph showing the difference of protein expression in the (B) four groups. The results are presented as the mean ± standard deviation (n=5). Statistical analysis was performed using one-way ANOVA with LSD post-hoc test. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, postsynaptic 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

f2-etm-0-0-3470: Western blotting showing the effects of castration and DHT intervention on the conversion from MCI to Alzheimer's dementia in SAMP8 mice. Western blot detected SYN, PSD95, Drebrin and CREB protein expression in the (A) castration, DHT and P8 groups. A statistical graph showing the difference of protein expression in the (B) four groups. The results are presented as the mean ± standard deviation (n=5). Statistical analysis was performed using one-way ANOVA with LSD post-hoc test. **P<0.01. DHT, dihydrotestosterone; SAMP8, senescence-accelerated mouse prone 8; SYN, synaptophysin; PSD95, postsynaptic density protein 95; CREB, cAMP-response element binding protein; Drebrin, developmentally regulated brain protein.
Mentions: The protein bands for CREB in hippocampus were clearly visible in the different groups (Fig. 2). The integrated OD (IOD) value of CREB in the castration group was 0.589±0.075, which was significantly lower compared to the P8 group at 1.113±0.152 (P<0.01). However, the IOD value for CREB in the DHT group was 1.032±0.118, which was significantly different compared to the castration group (P<0.01). The expression levels of SYN (0.453±0.074, 0.947±0.117, 0.891±0.126), PSD95 (0.109±0.007, 0.193±0.018, 0.205±0.025), and Drebrin (0.189±0.045, 0.632±0.058, 0.613±0.092) was consistent with that of CREB protein. There was a statistically significant difference (P<0.01) between the castration group and P8 groups (Table III).

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