Role of astrocyte aging in the pathogenesis of alzheimer`s disease

Alzheimer's disease (AD) is the most abundant severe and irreversible neurodegenerative disease in the world that affects people over 65 years old. The major hallmarks of AD pathology are the senile p-amyloid plaques, hyperphosphorylated neurofibrillary tangles, accompanied by severe neuroinflammation, synaptic disruption, neuronal degeneration and apoptosis, eventually triggering cerebral atrophy, memory loss and cognitive decline. The deposition and increase of p-amyloid levels in the brain induce the cascade of signals triggering production of neurotoxic molecules such as reactive oxygen species, nitric oxide, and proinflammatory cytokines and chemokines that cause neuroinflammation and neurodegeneration eventually resulting into dementia. Aging is the key risk factor for many inflammatory diseases including AD. However, the correlation of aging and AD is poorly investigated. Especially, the cytotoxic effects of p-amyloid in aging glial cells have been poorly explored. Human astrocytes are the most abundant CNS cells that undergo senescence with age and in response to stress. Therefore, it is hypothesized that sensitivity to p-amyloid may significantly change during in vitro senescence of astrocytes. The aim of this study is to investigate the mechanisms of cytotoxic actions of p-amyloid peptide in senescent astrocytes

Role of astrocyte aging in the pathogenesis of alzheimer`s disease

Alzheimer's disease (AD) is the most abundant severe and irreversible neurodegenerative disease in the world that affects people over 65 years old. The major hallmarks of AD pathology are the senile p-amyloid plaques, hyperphosphorylated neurofibrillary tangles, accompanied by severe neuroinflammation, synaptic disruption, neuronal degeneration and apoptosis, eventually triggering cerebral atrophy, memory loss and cognitive decline. The deposition and increase of p-amyloid levels in the brain induce the cascade of signals triggering production of neurotoxic molecules such as reactive oxygen species, nitric oxide, and proinflammatory cytokines and chemokines that cause neuroinflammation and neurodegeneration eventually resulting into dementia. Aging is the key risk factor for many inflammatory diseases including AD. However, the correlation of aging and AD is poorly investigated. Especially, the cytotoxic effects of p-amyloid in aging glial cells have been poorly explored. Human astrocytes are the most abundant CNS cells that undergo senescence with age and in response to stress. Therefore, it is hypothesized that sensitivity to p-amyloid may significantly change during in vitro senescence of astrocytes. The aim of this study is to investigate the mechanisms of cytotoxic actions of p-amyloid peptide in senescent astrocytes

Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea

Abstract Background The expression of vitamin D receptor in the normal endometrium and ovaries supports the role of vitamin D in local immunity and inflammatory cytokines regulation. Objective This study aimed to detect the relation between serum 25(OH)D and primary dysmenorrhea in Asian Adolescents. Methods Two hundred and five (205) adolescents complaining of primary dysmenorrhea (study group) were compared in this prospective study to matched controls (210 controls) after informed consent following the Helsinki Declaration. After thorough evaluation, including a thorough history and pelvic ultrasound examination, blood samples were collected from the studied adolescents to measure serum 25(OH)D and for vitamin D receptor TaqI (rs731236) genotyping. The studied adolescents’ data were analyzed using the Pearson’s correlation to detect the relation between serum 25(OH)D and primary dysmenorrhea (primary outcome). The secondary outcome measures the odds of primary dysmenorrhea in Asian adolescents with vitamin D receptor TaqI (rs731236) polymorphism. Results The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls (16.17 ± 7.36 versus 17.65 ± 6.36 ng/ml, respectively), (P = 0.01). The correlation analysis showed a significant negative correlation between the serum 25(OH)D and visual analogue scale of dysmenorrhea (r = -0.9003, P < 0.0001). The studied-dysmenorrhea cases with vitamin D receptor T/t and t/t genotypes had significantly lower serum 25(OH)D (16.7 ± 8.05 and 14.4 ± 4.1 ng/ml, respectively) compared to controls (18.97 ± 6.7 and 21.4 ± 2.45 ng/ml, respectively), (P = 0.02 and 0.004, respectively). The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea (OR 1367.2, P < 0.0001 and OR 106.2, P = 0.001, respectively). Conclusion The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls. The studied-dysmenorrhea cases with VDR T/t and t/t TaqI genotypes had significantly lower serum 25(OH)D compared to controls. The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea