Mechanism of depression as a risk factor in the development of Alzheimer’s disease: the function of AQP4 and the glymphatic system

Xia, Maosheng; Yang, Li; Sun, Guangfeng; Qi, Shuang; Li, Baoman

doi:10.1007/s00213-016-4473-9

Cited by 116 publications

(133 citation statements)

References 59 publications

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“…Brain tissue was immersed in 4% paraformaldehyde and cut into 50 μm slices. As our previous described, 20…”

Section: Immunohistochemistrymentioning

confidence: 59%

“…Total RNA was reverse transcribed and PCR amplification was performed in a Robo-cycler thermocycler, as our previous description. 20,22 Briefly, relative quantity of transcripts was assessed using five folds serial dilutions of RT product (200 ng). RNA quantity was normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) before calculating relative expression of DMT1 or Ndfip1.…”

Section: Quantitative Pcr (Qpcr)mentioning

confidence: 99%

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Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Xia¹,

Liang²,

Li³

et al. 2020

Preprint

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Metal implants are used worldwide, with millions of metal nails, plates and fixtures grafted during orthopaedic surgeries. Iron is the most common element of these metal implants. As time passes metal elements can be corroded and iron can be released from the implants in the form of ferric (Fe 3+ ) or ferrous (Fe 2+ ). These iron ions can permeate the surrounding tissues and enter circulation; importantly both Fe 3+ and Fe 2+ freely pass blood brain barrier (BBB). Can iron from implants represent a risk factor for neurological diseases? This remains an unanswered question. In this study, we discovered that the probability of metal implants delivered through orthopaedic surgeries was higher in patients of Parkinson's diseases (PD) or ischemic stroke than in healthy subjects. This finding instigated subsequent study of iron effects on neuronal cells. In experiments in vivo, we found that iron selectively decreased presence of divalent metal transporter 1 (DMT1) in neurones through increasing the expression of Ndfip1, which degrades DMT1 and rarely exists in glial cells. At the same time iron accumulation increased expression of DMT1 in astrocytes and microglial cells and triggered reactive astrogliosis and microglial activation. Facing the attack of excess iron, glial cells act as neuroprotectors to uptake more extracellular iron by up-regulating DMT1, whereas neurones limit iron uptake through decreasing DMT1 operation. Cerebral accumulation of iron was associated with impaired cognition, locomotion and mood. Excess iron thus affects neural cells and could increase the risk of neurodegeneration.

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“…Brain tissue was immersed in 4% paraformaldehyde and cut into 50 μm slices. As our previous described, 20…”

Section: Immunohistochemistrymentioning

confidence: 59%

Section: Quantitative Pcr (Qpcr)mentioning

confidence: 99%

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Xia¹,

Liang²,

Li³

et al. 2020

Preprint

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“…As per our previous description 27 , time of staying on rotating rod indicates motion balance ability. Each mouse was placed on a rotating bar, which was set to a rotation speed of up to 20 rpm during the test.…”

Section: Rotating Rod Testmentioning

confidence: 91%

“…The open field test is an anxiety-based test, as previously described 27 . The mice were placed in the centre square of an open field box (60 × 60 × 40 cm) divided into nine squares, and behaviours were recorded for 6 min.…”

Section: Open Field Testmentioning

confidence: 99%

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Fluoxetine improves behavioural deficits induced by chronic alcohol addiction by alleviating RNA editing of 5-HT_2C receptors in astrocytes

Liang

et al. 2019

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The alcoholism and major depressive disorder are common comorbidity, with alcohol-induced depressive symptoms being eased by selective serotonin re-uptake inhibitors (SSRIs), although the mechanisms underlying pathology and therapy are poorly understood. Chronic alcohol consumption affects the activity of serotonin 2C receptors (5-HT2CR) by regulating adenosine deaminases acting on RNA (ADARs) in neurones. Astrogliopathic changes contribute to alcohol addiction, while decreased release of ATP from astrocytes can trigger depressive-like behaviours in mice. In this study, we discovered that chronic alcohol addiction increased editing of RNA of 5-HT2CR via up-regulating the expression of ADAR2, consequnetly reducing the release of ATP from astrocytes induced by 5-HT2CR agonist, MK212. At the same time SSRI antidepressant fluoxetine decreased the expression of ADAR2 through the transactivation of EGFR/PI3K/AKT/cFos signalling pathway. Reduction in ADAR2 activity eliminated the RNA editing of 5-HT2CR in vivo and increased release of astroglial ATP which was suppressed by chronic alcohol consumption. Meanwhile, fluoxetine improved the behavioural and motor symptoms induced by alcohol addiction and decreased the alcohol intake. Our study suggests that the astrocytic 5-HT2CR contribute to alcohol addiction; fluoxetine thus can be used to alleviate depression, treat alcohol addiction and improve motor coordination.

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Enlarged perivascular spaces in patients with migraine: a case–control study based on 3T MRI

Yuan,

Li,

Tang

et al. 2023

Ann Clin Transl Neurol

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Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

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Mechanism of depression as a risk factor in the development of Alzheimer’s disease: the function of AQP4 and the glymphatic system

Cited by 116 publications

References 59 publications

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Fluoxetine improves behavioural deficits induced by chronic alcohol addiction by alleviating RNA editing of 5-HT_2C receptors in astrocytes

Enlarged perivascular spaces in patients with migraine: a case–control study based on 3T MRI

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Mechanism of depression as a risk factor in the development of Alzheimer’s disease: the function of AQP4 and the glymphatic system

Cited by 116 publications

References 59 publications

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Fluoxetine improves behavioural deficits induced by chronic alcohol addiction by alleviating RNA editing of 5-HT2C receptors in astrocytes

Enlarged perivascular spaces in patients with migraine: a case–control study based on 3T MRI

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Fluoxetine improves behavioural deficits induced by chronic alcohol addiction by alleviating RNA editing of 5-HT_2C receptors in astrocytes