Research progress on the interplay between intestinal microecology and cognitive dysfunction / 中华老年医学杂志

Cognitive impairment can be attributed to various causes.Its main manifestations include declines in learning, memory, understanding and executive function, and may be accompanied by varying degrees of psychiatric symptoms.Dementia is characterized by progressive deterioration in multiple cognitive domains that is severe enough to interfere with daily functioning.The pathogenesis of dementia is still unclear.In addition to the mainstream Aβ amyloid cascade hypothesis, recent research increasingly points to an association of microbial dysbiosis with many brain disorders.There is a direct or indirect link between gut bacteria and the central nervous system and consequently a new concept, the gut-brain axis, has been proposed.This paper will review recent advances in research on gut microbiota and cognitive function in the past five years, aiming to provide strategies for disease prevention and treatment.

Hypoxia aggravates Aβl-42-induced toxicity in human neuroblastoma cells through PAK1/LIMK1/cofilin pathway / 中华老年医学杂志

Objective To investigate the pathways by which hypoxia aggravates the neurotoxic effects of amyloid-beta protein (Aβ) on neurons.Methods Human neuroblastoma cells (SH-SY5Y cells) were cultured in vitro,and were divided into four groups:the control group,Aβ intervention group,hypoxia group,Aβ intervention plus hypoxia group.Quantitative real time polymerase chain reaction(qRT-PCR) was adopted to detect the mRNA expression levels of p21-activated kinase 1 (PAK1),LIM kinase 1 protein (LIMK1)and cofilin.Western blot was used to measure the protein levels of PAK1,LIMK1,phosphate-LIMK1 (P-LIMK1),cofilin and phosphate-cofilin (P-cofilin).Results After Aβ treatment,the activity of SH-SY5Y cells was decreased.Compared with the control group,the protein levels of PAK1,LIMK1,P-LIMK1,P-cofilin,and the mRNA expression levels of PAK1 and LIMK1 were decreased(all P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment with 10μmol/L Aβ.Compared with the Aβ intervention group,the protein levels of PAK 1,LIMK1,P-LIMK 1 and P-cofilin were decreased (all P ＜ 0.05),and the mRNA expression levels of PAK1 and LIMK1 were decreased(both P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment of SH-SY5Y cells with 10 μmol/L Aβ plus 2％ oxygen.Conclusions Aβ may reduce P-LIMK1 expression by inhibiting the activity of PAK1,thereby reducing the P-cofilin,increasing the formation of dephosphorylated cofilin,leading to neural cells damage,and hypoxia aggravates the neurotoxicity of Aβ through this pathway.

Role of TXNIP-mediated oxidative stress in delaying Alzheimer's disease by estrogen / 中南大学学报(医学版)

To study the functional mechanism of thioredoxin-interacting protein (TXNIP) in delaying Alzheimer's disease (AD) by estrogen.
 Methods: After estradiol (E2) treatment in Aβ-induced AD cell model, reactive oxygen species (ROS), TXNIP, and apoptosis levels were detected. After lentiviral infection with TXNIP overexpression, the effect of E2 on ROS and apoptosis were observed. In the AD rat model, the learning and memory ability and the expression of TXNIP in the hippocampus were observed in the presence of E2. After overexpressing TXNIP, the effect of E2 on the learning and memory ability of AD rat model was observed.
 Results: ROS, TXNIP and apoptosis levels were enhanced in AD cell model, while E2 treatment reduced ROS, TXNIP and apoptosis levels in AD cell model. After enhancing TXNIP, E2 treatment reduced ROS and apoptosis levels in AD cell model. Similar to the cell experiment, E2 enhanced the learning and memory ability in the AD rat model and inhibited the expression of TXNIP in brain, while TXNIP overexpression attenuated the effect of E2 on learning and memory ability in the AD rats.
 Conclusion: Estrogen can inhibit the expression of TXNIP in nerve tissue, reduce nerve damage, and delay the development of AD.

Effect of ten-eleven translocation protein on the expression of amyloid precursor protein and β-site APP cleaving enzyme-1 in SH-SY5Y and IMR-32 cells in folic acid deficiency and the underlying mechanisms / 中华老年医学杂志

Objective To investigate the effect of ten-eleven translocation protein on the proliferation of human neuroblastoma cell lines SH-SY5Y and IMR 32 and the expression of amyloid precursor protein,PS1,and β site APP cleaving enzyme 1 in the absence of folic acid and possible mechanisms involved.Methods SH-SY5Y and IMR-32 cells were cultured in vitro and divided into the folic acid deficiency group (0 mg/L),the low folic acid group (1mg/L),and the normal control group (4mg/L).The MTT method was used to observe cell proliferation,and RT-PCR was adopted to detect the mRNA expression of APP,PS1,BACE1,DNMTs and TETs in the cells in real-time.Besides,we generated a stable low-level TET1 expression cell line,and compared the expression with that in a negative control group.Furthermore,the expression of fluorescent protein was observed by fluorescence inverted microscope,cell proliferation was measured by the MTT assay,and mRNA levels of TET1,APP,PS1,and BACE1 were detected by RT-PCR.Results (1) In the folic acid deficiency group and the low folic acid group,cell proliferation of SH-SY5Y after 120 h and of IMR-32 cell after 144 h significantly decreased (P＜0.001).The mRNA levels of APP,PS1,BACE1,DNMT1,DNMT3a,DNMT3b,TET1,TET2,and TET3 in SH-SY5Y cells increased (F=80.315,35.386,101.979,786.407,80.331,131.545,28.000,9.165,and 102.167,all P＜0.05);the mRNA levels of APP,PS1,BACE1,DNMT1,DNMT3b,TET1,TET2,and TET3 in IMR-32 cells also rose (F=12.283,93.669,40.815,157.234,24.835,147.594,54.794,and 73.068,all P＜0.05).(2) Generation of a stable low-level TET1 expression cell line:The mRNA level of TET1 in the low expression group (SH-SY5Y-shTET1) was 0.25± 0.02,which was significantly lower than that in the negative control group (1.00±0.09) (P=0.007);the mRNA level of TET1 in the low expression group (IMR-32-shTET1) was 0.28 ±0.07,significantly lower than that in the negative control group (1.00±0.01) (P=0.003).(3)The proliferative ability of the low expression groups (SH-SY5Y-shTET1 and IMR-32-shTET1) was significantly higher than that in the negative control group (P＜0.01).The mRNA levels of APP and BACE1 decreased (P＜0.01 or P＜0.05)Conclusion In the human neuroblastoma cell lines SH-SY5Y and IMR-32,folic acid deficiency up-regulates the expression of TETs,increases the expression of APP and BACE1 in the cells by TET protein demethylation,and inhibits cell growth.

Change in heme oxygenase-1 level in cerebrospinal fluid and serum and its correlation with the rating scale in patients with mild cognitive impairment / 中华老年医学杂志

Objective To explore the change in heme oxygenase-1 (HO-1) level in cerebrospinal fluid(CSF)and serum in patients with mild cognitive impairment(MCI),and the correlation between HO-1 and the rating scale,to provide a new marker for the diagnosis of MCI.Methods The HO-1 levels in CSF and serum in 45 MCI patients (MCI group) and 85 normal cases (control group) were analyzed with sensitive enzyme linked immunosorbent assays (ELISA).MMSE and MoCA scores were evaluated.Results The level of HO-1 was higher in MCI group than in control group both in CSF [(631.38±32.17)vs(480.75±17.98)ng/ L,P＜0.05],and in serum [(612.52±111.48)vs.(384.16±56.86)ng/ L,P＜0.05].The MCI and normal people HO-1 level had no significant difference between CSF group and serum group (P＞0.05).In MCI group,the levels of serum and CSF HO-1 had a positive correlation with MMSE scores (P＜0.05),but had no obvious correlation with MoCA scores (P＞0.05).In the normal group,the level of HO-1 was negatively related with MMSE scores in serum and CSF,and with MoCA scores in CSF (P＜0.05),but no obvious correlation in serum (P＞0.05).The levels of serum and CSF HO-1 had no obvious correlation with age in both groups (P＞0.05).Conclusions HO-1 concentration in both CSF and serum is significantly higher in MCI group than in normal group,and positively related with MMSE score.Thus the increase of HO-1concentration in both CSF and/or serum might be a new marker for the diagnosis of MCI.

A case-control study on the indexes of Stroop color-word test in the patients with ischemic cerebrovascular disease / 中华老年医学杂志

ObjectiveTo explore the abilities of automatic processing,controlled processing,selective attention by Stroop color-word test in patients with ischemic cerebrovascular disease.Methods124 patients (aged 60-90 years) with ischemic cerebrovascular disease and 126 cases with age and civilization matched healthy people were examined by Stoop color-word test (SCWT).The SCWT indexes were compared between two groups.Results Reading time of card 1,timeconsuming and error of card 2,4 and Stroop interference effects (SIE) in SCWT had significantly decreased in the patients than in the healthy people (all P＜0.05).ConclusionsThe abilities of controlled processing and selective attention,but not automatic processing are damaged in patients with ischemic cerebrovascular disease.

The Expression of ET-3 and GFAP in the Layers Ⅲ-Ⅵ of Frontal and Parietal Lobes of Mice Following Cerebral Ischemia/Reperfusion / 中国医师杂志

Objective To explore the relationship between ischemia/reperfusion (IR) and the expression ET-3 and GFAP. Methods Thirty-six adult male mice were randomly divided into three groups: ⑴ ischemia/reperfusion group(IR,n=24), bilateral common carotid arteries(BCCA) of mice were ligated for 7 minutes and reperfused for 1day,3day,5day and 10day; ⑵ a sham operation group (SO, n=6); ⑶ normal control group(NG, n=6). The ET-3 and GFAP expressions in the layers Ⅲ-Ⅵ of frontal and parietal lobes of mice in the three groups was detected by immunohistochemisty. Results The expressions of ET-3 and GFAP in the layers Ⅲ-Ⅵ of frontal and parietal lobes significantly increased in I/R group(P

Expression of ubiquitin in neurofibrillary tangles and senile plaque neurites in hippocampal formation of Alzheimer's disease brain / 中华神经科杂志

Objectives To detect the expression and distribution of ubiquitin in neurofibrillary tangles(NFT) and senile plaque neurites in the hippocampal formation of Alzheimer's disease brain and explore the significance of ubiquitin in pathological mechanism of Alzheimer's disease.Methods The expression of ubiquitin in the hippocampal formation of 7 patients with Alzheimer's disease and 5 non-dementia elderly was detected using immunohistochemical technique.Results Neurofibrillary tangles and senile plaque neuritis were labeled by the antibody of ubiquitin in hippocampal formation of Alzheimer's disease brain, but pretangle neurons were not stained. Containing NFT neurons stained by ubiqutin antibody immunoreactive products were distributed more in the CA1 and CA2 (42.13?0.65, 30.57?0.78 respectively)than those in CA3 and CA4 (12.43?0.24?18.34?0.81 respectively)of the hippocampal formation (P