Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

Wang, Xu; Li, Guangjian; Hu, Haixia; Ma, Chi; Ma, Dihui; Liu, Xiaoliang; Jiang, Xiaoming

doi:10.1515/tnsci-2016-0022

Cited by 24 publications

(21 citation statements)

References 43 publications

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“…Following water maze testing, blood and serum were acquired. Routine indices and cytokines (Wang et al, 2016) were measured and the brains of the animals dissected. Four brains from each group were fixed in 4% paraformaldehyde solution and prepared as paraffin sections.…”

Section: Methodsmentioning

confidence: 99%

Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Lai

Guo²,

Chen³

et al. 2019

Front. Pharmacol.

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Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer’s disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, Ganoderma lucidum , for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D -galactose to induce accelerated aging showed that alcohol extracts of G. lucidum contained the main active anti-aging extract. The effects on DNA methylation of these G. lucidum extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from G. lucidum . Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of G. lucidum , including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that G. lucidum alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ 1-42 . We concluded that alcohol extracts from G. lucidum , including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.

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Section: Methodsmentioning

confidence: 99%

Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Lai

Guo²,

Chen³

et al. 2019

Front. Pharmacol.

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show abstract

“…Following the MWM, the blood and serum were acquired, and the brains of the animals were dissected. Routine index and cytokines ( Wang et al, 2016 ), including the production of cytokines interleukins [(1L)-1α, 1L-2, 1L-8, 1L-10, 1L-11, IL-12], tumor necrosis factor (TNF)-γ, TNF-α, vascular endothelial growth factor (VGEF), human macrophage inflammatory protein-1α (MIP-α), and macrophage colony-stimulating factor (M-CSF), activities of malondialdehyde (MDA), total superoxide dismutase (T-SOD), catalase (CAT), glutathione reductase (GSH-Px), and levels of acetylcholine (ACh), acetylcholinesterase (AChE), and Na + /K + -ATPase, and some monoamine neurotransmitters, were measured.…”

Section: Methodsmentioning

confidence: 99%

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis

Chen

Yang

et al. 2017

Front. Aging Neurosci.

185

118

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Gut microbiota influences the central nervous system disorders such as Alzheimer’s disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology.

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“…After completion of antibody injection, drugs were given. The following procedures were performed as described in our previous publication (22). Animals were cannulated with an L-shaped stainless steel cannula aimed at the lateral ventricle (coordinates: 3.7 mm posterior to the bregma, 4.1 mm lateral to the midline, and 3.5 mm under the dura).…”

Section: Methodsmentioning

confidence: 99%

Neuronal NMDAR Currents of the Hippocampus and Learning Performance in Autoimmune Anti-NMDAR Encephalitis and Involvement of TNF-α and IL-6

Wang

Liu

et al. 2019

Front. Neurol.

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Among autoimmune encephalitis, patients with anti-N-methyl D- aspartate receptor (NMDAR) encephalitis typically present epileptic seizures, memory deficits and psychiatric symptoms. However, the signal mechanisms leading to the functional disorders of autoantibodies are largely unclear. In this study, anti-NMDAR antibody was administered into dentate gyri against the NR1 subunit of the NMDAR. The purpose of the study examined the effects of pro-inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on neuronal NMDAR currents of the hippocampus in rats with anti-NMDAR encephalitis and we further determined the role played by TNF-α and IL-6 in modulating learning performance. In results, we observed a decrease in amplitude of the NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) in the hippocampal neurons of animals treated with anti-NMDAR. In those rats with anti-NMDAR, we also observed impaired learning performance in the Morris water maze and spatial working memory test. Of note, cerebral infusion of TNF-α and IL-6 worsened NMDAR-EPSCs and this was accompanied with exaggeration of impaired learning performance. In conclusion, our findings suggest that the role played by neuroinflammation in exacerbating the memory impairment found in animals treated with anti-NMDAR. Anti-inflammation is a potential target in improving the memory impairment induced by anti-NMDA encephalitis.

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Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

Cited by 24 publications

References 43 publications

Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis

Neuronal NMDAR Currents of the Hippocampus and Learning Performance in Autoimmune Anti-NMDAR Encephalitis and Involvement of TNF-α and IL-6

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