Protective effects of testosterone on cognitive dysfunction in Alzheimer’s disease model rats induced by oligomeric beta amyloid peptide 1-42

Huo, Dong-Sheng; Sun, Jian-Fang; Zhang, Baifeng; Yan, Xu-Sheng; Wang, He; Jia, Jianxin; Yang, Zhenhua

doi:10.1080/15287394.2016.1193114

Cited by 33 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SYN is a glycoprotein that is located on the membranes of presynaptic vesicles, and SYN expression can accurately and objectively reflect the distribution and density of synapses ( 59), since SYN is closely associated with synapse formation and reconstruction (60). The degree of cognitive decline in animal models of AD has been correlated with changes in SYN expression in the hippocampus (17,(61)(62)(63)(64). The present study demonstrated that EE exposure increased the expression of SYN in the hippocampal CA1 region, which further indicates that EE exposure was able to increase neuronal synapses and improve synaptic plasticity in SAMP8 mice.…”

Section: Discussionmentioning

confidence: 99%

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence‑accelerated mouse prone 8 mice

Hao

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

A previous study demonstrated that middle-aged (5-6 months of age) senescence-accelerated mouse prone 8 (SAMP8) mice can be used as animal models of mild cognitive impairment (MCI). An enriched environment (EE) can mitigate cognitive decline and decrease the pathological changes associated with various neurodegenerative diseases. In the present study, the learning-memory abilities of SAMP8 mice during the MCI phase (5 months of age) was evaluated and neuropathological changes in the hippocampus were examined after the mice were exposed to an EE for 60 days. In the Morris water maze test, EE-exposed mice demonstrated significantly decreased escape latency and increased time spent in the target quadrant and number of platform crossings compared with control mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining showed that EE-exposed mice had reduced neuronal apoptosis and increased number of surviving neurons compared with control mice. Golgi staining, transmission electron microscopy, and immunohistochemical staining demonstrated that EE-exposed mice exhibited increased dendritic spine densities among secondary and tertiary apical dendrites; increases in synaptic numerical density, synaptic surface density, and expression of synaptophysin; and reduced deposition of amyloid-β (Aβ) and expression of amyloid-precursor protein (APP) in the hippocampal CA1 region compared with control mice. These results demonstrate that EE exposure effectively decreases neuronal loss and regulates neuronal synaptic plasticity by reducing the expression of APP and the deposition of Aβ in the hippocampal CA1 region, thereby mitigating cognitive decline in SAMP8 mice during the MCI phase and delaying the progression from MCI to Alzheimer's disease.

show abstract

Section: Discussionmentioning

confidence: 99%

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence‑accelerated mouse prone 8 mice

Hao

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…Emerging evidences have reported that age‐related decrease in serum androgen in men facilitates the development of AD pathology and Aβ deposition, which may be conducive for their vulnerability to AD (Götz et al, ; Hardy & Higgins, ; Huo et al, ). However, the factors underlying the AR‐mediated regulation of APP and Aβ remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells

2019

View full text Add to dashboard Cite

Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). Androgens function by binding to the androgen receptor (AR). Both androgen and RNA‐binding protein PSF play a role in the pathology of AD. However, the involvement of AR and PSF in APP regulation in neuron has not been investigated. Here, we explored the regulatory mechanism of APP expression by AR and PSF using neuron‐derived cells. We demonstrated that androgen up‐regulates the production of APP at the mRNA and protein levels. This induction is enhanced by AR over‐expression and inhibited by its silencing. One candidate AR‐binding region was identified in the intron region of APP and validated its activity as AR‐dependent enhancer by the luciferase assay. Furthermore, the public transcriptome data of brain tissues of mice indicated that APP is regulated by PSF post‐transcriptionally. We observed a decreased expression of APP after PSF knockdown and interaction of PSF with the APP transcript. Moreover, we revealed that silencing of PSF inhibited the stability of the APP mRNA. Thus, these results presented a new regulatory mechanism of APP expression by androgen through AR‐mediated transcription and PSF at the post‐transcriptional level that might be associated with the occurrence of AD.

show abstract

“…Interestingly the steroid-hormone testosterone-activated transcription factor-signaling AR (ANDR) is known to exert regulatory effects on synaptic plasticity and improve cognitive deficits in AD patients and transgenic rodent models for AD (TgAD) but the underlying mechanisms of androgenic action on cognitive performance remain unclear. Testosterone, via the AR, increases synaptophysin expression and improves synaptic plasticity and cognitive metrics in both Aβ42 peptide-hippocampal injected male rats and in the senescence-accelerated mouse prone 8 (SAMP8) TgAD murine model (Huo et al, 2016; Jia et al, 2016). In a recent double-blind, placebo-controlled, between-subject designed study, exogenous administration of testosterone to healthy adult men potentiated the AR-enriched hippocampus, amygdala and hypothalamus—anatomical regions known to be involved in the stimulation of aggressive behavior (Carré et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Genetics of Aggression in Alzheimer’s Disease (AD)

Lukiw

Rogaev

2017

Front. Aging Neurosci.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD. These genes encoded on five different chromosomes (chr) include the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF; chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1). Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1) are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii) five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the development, onset and/or propagation of schizophrenia. The magnitude of the expression of genes implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype.

show abstract

Protective effects of testosterone on cognitive dysfunction in Alzheimer’s disease model rats induced by oligomeric beta amyloid peptide 1-42

Cited by 33 publications

References 33 publications

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence‑accelerated mouse prone 8 mice

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence‑accelerated mouse prone 8 mice

Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells

Genetics of Aggression in Alzheimer’s Disease (AD)

Contact Info

Product

Resources

About