Brain, Behavior, and Immunity - Health

Alzheimer's disease (AD) is a progressively neurodegenerative disease without effective treatment. Here, we reported that the levels of expression and enzymatic activity of phosphatase magnesium-dependent 1A (PPM1A) were both repressed in brains of AD patient postmortems and 3 × Tg-AD mice, and treatment of adeno-associated virus (AAV)-ePHP-overexpression (OE)-PPM1A for brain-specific PPM1A overexpression or the new discovered PPM1A activator Miltefosine (MF, FDA approved oral anti-leishmanial drug) for PPM1A enzymatic activation improved the AD-like pathology in 3 × Tg-AD mice. The mechanism was intensively investigated by assay against the 3 × Tg-AD mice with brain-specific PPM1A knockdown (KD) through AAV-ePHP-KD-PPM1A injection. MF alleviated neuronal tauopathy involving microglia/neurons crosstalk by both promoting microglial phagocytosis of tau oligomers via PPM1A/Nuclear factor-κb (NF-κB)/C-X3-C Motif Chemokine Receptor 1 (CX3CR1) signaling and inhibiting neuronal tau hyperphosphorylation via PPM1A/NLR Family Pyrin Domain Containing 3 (NLRP3)/tau axis. MF suppressed microglial NLRP3 inflammasome activation by both inhibiting NLRP3 transcription via PPM1A/NF-κB/NLRP3 pathway in priming step and promoting PPM1A binding to NLRP3 to interfere NLRP3 inflammasome assembly in assembly step. Our results have highly addressed that PPM1A activation shows promise as a therapeutic strategy for AD and highlighted the potential of MF in treating this disease.

Jianlu Lv

Xingyi Shen

Xinya Shen

Xiaoqian Li

Zhuoying Jin

Xingnan Ouyang

Jian Lu

Danyang Zhu

Jiaying Wang

Xu Shen

Brain, behavior, & immunity - health

Brain Behav Immun Health

Miltefosine as a PPM1A activator improves AD-like pathology in mice by alleviating tauopathy via microglia/neurons crosstalk.

米替福新作为PPM1A激活剂通过小胶质细胞/神经元交叉对话减轻Tau病变，改善小鼠类似阿尔茨海默病病理。

Recent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study is a placebo controlled randomized study comparing sertraline vs. placebo in patients with MDD to identify biological markers of therapy resistance. Association of baseline volumes of the lateral ventricles (LVV), choroid plexus volume (CPV) and volume of segments of the CC with treatment response after 4 weeks treatment was evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline vs. placebo was observed, therefore the study characterized prognostic markers of response in the pooled population. Change in depression severity was identified by the ratio of the Hamilton-Depression rating scale 17 (HAMD-17) at week 4 divided by the HAMD-17 at baseline (HAMD-17 ratio). Volumes of the lateral ventricles and choroid plexi were positively correlated with the HAMD-17 ratio, indication worse outcome with larger ventricles and choroid plexus volumes, whereas the volume of the central-anterior corpus callosum was positively correlated with the HAMD-17 ratio. Responders (n = 54) had significantly smaller volumes of the lateral ventricles and CP compared to non-responders (n = 117), whereas the volume of mid-anterior CC was significantly larger compared to non-responders (n = 117), confirming our previous findings. In an exploratory way associations between enlarged LVV and CPV and signs of lipid dysregulation were observed. In conclusion, we confirmed that volumes of lateral ventricles, choroid plexi and the mid-anterior corpus callosum are associated with clinical improvement of depression and may be indicators of metabolic/inflammatory activity.

Harald Murck

Maurizio Fava

Cristina Cusin

Cherise Chin Fatt

Madhukar Trivedi

Brain Behavior & Immunity - Health

Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study

脑室和脉络丛形态作为重度抑郁症治疗反应的预测因子：EMBARC研究的发现

Subarachnoid hemorrhage (SAH), accounting for ∼5% of all strokes, represents a catastrophic subtype of cerebrovascular accident. SAH predominantly results from intracranial aneurysm ruptures and affects ∼30,000 individuals annually in the United States and ∼6 individuals per 100,000 people worldwide. Recent studies have implicated that administering mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may be beneficial in inducing neuroprotective and antiinflammatory effects following SAH. EVs are nanosized particles bound by a lipid bilayer. MSC-EVs comprise a therapeutic cargo of nucleic acids, lipids, and proteins, having the promise to ease SAH-induced long-term brain impairments. This review evaluated the findings of published studies on the therapeutic efficacy of MSC-EVs in the context of SAH. A growing body of evidence points out the therapeutic potential of MSC-EVs for improving brain function in animal models of SAH. Specifically, studies demonstrated their ability to reduce neuronal apoptosis and neuroinflammation and enhance neurological recovery through neuroprotective and antiinflammatory mechanisms. Such outcomes reported in various studies suggest that MSC-EVs hold great potential as a novel and minimally invasive approach to ameliorate SAH-induced neurological damage and improve patient outcomes. The review also discusses the limitations of EV therapy and the required future research efforts toward harnessing the full potential of MSC-EVs in treating SAH.

Kiran Sankarappan

Ashok K Shetty

Promise of mesenchymal stem cell-derived extracellular vesicles for alleviating subarachnoid hemorrhage-induced brain dysfunction by neuroprotective and antiinflammatory effects

间充质干细胞衍生的细胞外囊泡通过神经保护和抗炎作用减轻蛛网膜下腔出血引起的脑功能障碍的潜力

Aidan D. Tyrrell

Giulia Cisbani

Mackenzie E. Smith

Chuck T. Chen

Yue-Tong Chen

Raphael Chouinard-Watkins

Kathryn E. Hopperton

Ameer Y. Taha

Richard P. Bazinet

Lipid Mediators in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review

阿尔茨海默病患者死后脑样本中的脂质介质：系统综述

R. Bortoletto

C. Comacchio

M. Garzitto

F. Piscitelli

M. Balestrieri

M. Colizzi

Palmitoylethanolamide Supplementation for Human Health: A State-Of-The-Art Systematic Review of Randomized Controlled Trials in Patient Populations

棕榈酰乙醇酰胺补充对人类健康的影响：基于患者人群随机对照试验的最新系统综述

Pierluigi Catapano

Mario Luciano

Salvatore Cipolla

Daniela D'Amico

Alessandra Cirino

Maria Chiara Della Corte

Gaia Sampogna

Andrea Fiorillo

What is the relationship between exposure to environmental pollutants and severe mental disorders? A systematic review on shared biological pathways

环境污染物暴露与严重精神障碍之间的关系是什么？关于共享生物途径的系统综述

Shixin Lai

Xiaomin Wu

Yue Liu

Bo Liu

Haiqi Wu

Kongyang Ma

Interaction between Th17 and Central Nervous System in Multiple Sclerosis

Th17细胞与中枢神经系统在多发性硬化中的相互作用

Kimberley A. Stephenson

Aaron Barron

Mark G. Rae

Dervla O’Malley

Inhibition of hippocampal interleukin-6 receptor-evoked signalling normalises long-term potentiation in dystrophin-deficient mdx mice.

抑制海马白细胞介素-6受体信号传导可正常化肌营养不良蛋白缺乏型mdx小鼠的长时程增强。

Abbreviation	Brain Behav. Immun. Health
Journal Impact	3.88
Quartiles(Global)	PSYCHIATRY(Q1)

ISSN	2666-3546
h-index	28

Publication Information	Publisher: Elsevier Inc.，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2020，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%
Journal Fees	$2500Details
Average review cycle	网友分享经验：8 Weeks

Brain, Behavior, and Immunity - Health

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Miltefosine as a PPM1A activator improves AD-like pathology in mice by alleviating tauopathy via microglia/neurons crosstalk.

Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study

Promise of mesenchymal stem cell-derived extracellular vesicles for alleviating subarachnoid hemorrhage-induced brain dysfunction by neuroprotective and antiinflammatory effects

Lipid Mediators in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review

Palmitoylethanolamide Supplementation for Human Health: A State-Of-The-Art Systematic Review of Randomized Controlled Trials in Patient Populations

What is the relationship between exposure to environmental pollutants and severe mental disorders? A systematic review on shared biological pathways

Lipid Mediators in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review

Palmitoylethanolamide Supplementation for Human Health: A State-Of-The-Art Systematic Review of Randomized Controlled Trials in Patient Populations

Interaction between Th17 and Central Nervous System in Multiple Sclerosis

Inhibition of hippocampal interleukin-6 receptor-evoked signalling normalises long-term potentiation in dystrophin-deficient mdx mice.