Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations.

OBJECTIVE: To explore the mechanism involved in variable phenotypes of epilepsy models induced by γ-aminobutyric acid type A γ2 subunit (GABRG2) mutations. METHODS: The zebrafish carrying wild-type (WT) GABRG2, mutant GABRG2(P282S), GABRG2(F343L) and GABRG2(I107T) were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video-Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio-signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different GABRG2 mutations. RESULTS: The established Tg(hGABRG2P282S ) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in Tg(hGABRG2P282S ) zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of Tg(hGABRG2P282S ) zebrafish. In addition, the behavioral activity, production of pro-inflammatory factors, and activation of the IL-2 receptor signal pathway varied among the three mutant zebrafish lines. CONCLUSION: We successfully established transgenic zebrafish epileptic models expressing human mutant GABRG2(P282S), in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS/JAK/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by GABRG2 mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.

Blood SSR1: A Possible Biomarker for Early Prediction of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease associated with age. Early diagnosis of PD is key to preventing the loss of dopamine neurons. Peripheral-blood biomarkers have shown their value in recent years because of their easy access and long-term monitoring advantages. However, few peripheral-blood biomarkers have proven useful. This study aims to explore potential peripheral-blood biomarkers for the early diagnosis of PD. Three substantia nigra (SN) transcriptome datasets from the Gene Expression Omnibus (GEO) database were divided into a training cohort and a test cohort. We constructed a protein-protein interaction (PPI) network and a weighted gene co-expression network analysis (WGCNA) network, found their overlapping differentially expressed genes and studied them as the key genes. Analysis of the peripheral-blood transcriptome datasets of PD patients from GEO showed that three key genes were upregulated in PD over healthy participants. Analysis of the relationship between their expression and survival and analysis of their brain expression suggested that these key genes could become biomarkers. Then, animal models were studied to validate the expression of the key genes, and only SSR1 (the signal sequence receptor subunit1) was significantly upregulated in both animal models in peripheral blood. Correlation analysis and logistic regression analysis were used to analyze the correlation between brain dopaminergic neurons and SSR1 expression, and it was found that SSR1 expression was negatively correlated with dopaminergic neuron survival. The upregulation of SSR1 expression in peripheral blood was also found to precede the abnormal behavior of animals. In addition, the application of artificial intelligence technology further showed the value of SSR1 in clinical PD prediction. The three classifiers all showed that SSR1 had high predictability for PD. The classifier with the best prediction accuracy was selected through AUC and MCC to construct a prediction model. In short, this research not only provides potential biomarkers for the early diagnosis of PD but also establishes a possible artificial intelligence model for predicting PD.

p75NTR Interacts with the Zinc Finger Protein Glis2 and Participates in Neuronal Apoptosis Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a serious condition with a particularly high mortality rate. Gli-similar 2 (Glis2) has been reported to play an important role in the pathogenesis of ICH; however, its underlying mechanisms and biological significance remains unclear. In the present study, a specific interaction between Glis2 and p75NTR, a member of the tumor necrosis factor receptor superfamily, was identified both in vivo and in vitro. These experiments further indicated that p75NTR may interact with Glis2, and that the complex was transported into the nucleus, initially, inducing neuronal death. Furthermore, the mechanism of neuronal death was explored, and may have been mediated via the activation of the mitochondrial-dependent apoptotic pathway, and this was further investigated in the pathogenesis of ICH in rats in vivo. The study may provide evidences for regulating p75NTR-Glis2 complex as a potential reliable treatment for the secondary damage following ICH.

Astrocyte Pannexin 1 Suppresses LPS-Induced Inflammatory Responses to Protect Neuronal SH-SY5Y Cells.

Reactive astrogliosis is a key hallmark of inflammatory responses in the pathogenesis of brain injury, including Parkinson's disease (PD), but its role and regulatory mechanisms are not fully understood. Pannexin 1 (Panx 1) is a membrane channel that mediates substance release in many neurodegenerative diseases. However, the role of astrocyte Panx 1 in the regulation of PD-like neuroinflammation remains elusive. Here, we characterized the expression of Panx 1 in isolated primary astrocytes and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. The functions of Panx 1 in inflammatory cytokines expression and the viability of neuronal SH-SY5Y cells were examined in cultured cells treated with lipopolysaccharide (LPS) and 1-methyl-4-phenylpyridinium (MPP+). We found that Panx 1 expression was significantly increased under both LPS- and MPP+-treated conditions. Panx 1 downregulation suppressed LPS-induced pro-inflammatory cytokine expression but did not significantly affect MPP+-induced astrocyte apoptosis or inflammatory cytokine expression through treatment with the Panx 1 inhibitor carbenoxolone (CBX) and Panx 1 siRNA. Moreover, silencing Panx 1 in reactive astrocytes had a potentially protective effect on the viability of neuronal SH-SY5Y cells. Therefore, we propose that Panx 1 may serve as a key regulator in reactive astrocytes to intervene in the inflammatory response and maintain neuronal viability in the context of PD-like conditions.

SKP-SCs transplantation alleviates 6-OHDA-induced dopaminergic neuronal injury by modulating autophagy.

Parkinson's disease is a common neurodegenerative disease. Cell transplantation is a promising therapeutic option for improving the survival and function of dopaminergic neurons, but the mechanisms underlying the interaction between the transplanted cells and the recipient neurons remain to be studied. In this study, we investigated the effects of skin precursor cell-derived Schwann cells (SKP-SCs) directly cocultured with 6-OHDA-injured dopaminergic neurons in vitro and of SKP-SCs transplanted into the brains of 6-OHDA-induced PD mice in vivo. In vitro and in vivo studies revealed that SKP-SCs could reduce the damage to dopaminergic neurons by enhancing self-autophagy and modulating neuronal autophagy. Thus, the present study provides the first evidence that cell transplantation mitigates 6-OHDA-induced damage to dopaminergic neurons by enhancing self-autophagy, suggesting that earlier transplantation of Schwann cells might help alleviate the loss of dopaminergic neurons.

Role of the Peripheral Nervous System in PD Pathology, Diagnosis, and Treatment.

Studies on Parkinson disease (PD) have mostly focused on the central nervous system-specifically, on the loss of mesencephalic dopaminergic neurons and associated motor dysfunction. However, the peripheral nervous system (PNS) is gaining prominence in PD research, with increasing clinical attention being paid to non-motor symptoms. Researchers found abnormal deposition of α-synuclein and neuroinflammation in the PNS. Attempts have been made to use these pathological changes during the clinical diagnosis of PD. Animal studies demonstrated that combined transplantation of autologous peripheral nerves and cells with tyrosine hydroxylase activity can reduce dopaminergic neuronal damage, and similar effects were observed in some clinical trials. In this review, we will systematically explain PNS performance in PD pathology and its clinical diagnostic research, describe PNS experimental results [especially Schwann cell (SC) transplantation in the treatment of PD animal models] and the results of clinical trials, and discuss future directions. The mechanism by which SCs produce such a therapeutic effect and the safety of transplantation therapy are briefly described.

PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons.

BACKGROUND: Prostaglandin E1 (PGE1) exerts various pharmacological effects such as membrane stabilization, anti-inflammatory functions, vasodilation, and platelet aggregation inhibition. We have previously demonstrated that PGE1 has a beneficial impact on patients suffering from intracerebral hemorrhage (ICH). The related mechanism underlying PGE1's beneficial effect on ICH treatment needs further exploration. METHODS: The present study elucidates the mechanism of PGE1 on ICH treatment using a neuronal apoptosis model in vitro. The mouse primary cortical neurons were pretreated with different concentrations of PGE1, followed by the treatment with hemin, the main catabolite in whole blood, to mimic the clinical ICH. RESULTS: Comparing with the vehicle-treated group, PGE1 prevented cultured cortical neurons from the accumulation of inhibited intracellular levels of reactive oxygen species (ROS), amelioration of mitochondrial membrane potential, and hemin-induced apoptosis. The reduction of ROS and apoptosis were associated with the up-regulation of Heme oxygenase-1 (HO-1) expression. Knockdown of nuclear transcription factor erythroid 2-related factor (Nrf2) by siRNA attenuated the upregulation of HO-1 as well as the protective effect of PGE1. CONCLUSIONS: Our work suggests that the Nrf2/HO-1 molecular pathway may play a crucial role in treating ICH patients with PGE1 and may represent novel molecular targets, resulting in discovering new drugs for ICH treatment.

Effects of homocysteine-induced endoplasmic reticulum protein on endoplasmic reticulum stress, autophagy, and neuronal apoptosis following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is defined as bleeding into the brain parenchyma with a high mortality and morbidity rate. Unfortunately, it remains an unresolved medical problem. Therefore, it is necessary to find ways to reduce cellular apoptosis after ICH. Homocysteine-induced endoplasmic reticulum protein (HERP), a 54 kD transmembrane protein, is an early stress response protein encoded by ubiquitin-like domain member 1 (Herpud1) gene. In the present work, our group investigated the role of HERP after ICH and hemin stimulation, HERP expression was examined in mouse and primary cortical neurons after ICH and hemin stimulation by western blot and Immunofluorescent labeling. Using shRNA-HERP plasmid and recombinant adenovirus, we also investigated how HERP affected neuronal apoptosis after ICH and hemin stimulation. In addition, behavioral evaluation was used to ensure our models' success. In vivo and vitro studies, the expression of HERP was increased following ICH and hemin-exposed primary cortical neurons. HERP depletion activated the endoplasmic reticulum (ER) stress pathway and apoptosis in hemin-exposed primary cortical neurons, but inhibited autophagy in hemin-exposed primary cortical neurons. Overexpression of HERP inhibited the ER stress pathway and apoptosis, but activated autophagy in hemin-exposed primary cortical neurons. Consequently, we confirm that HERP plays a protective role in ICH model.

Skin-derived precursor Schwann cells protect SH-SY5Y cells against 6-OHDA-induced neurotoxicity by PI3K/AKT/Bcl-2 pathway.

Skin-derived precursors (SKPs) are self-renewing and pluripotent adult stem cell sources that have been successfully obtained and cultured from adult tissues of rodents and humans. Skin-derived precursor Schwann cells (SKP-SCs), derived from SKPs when cultured in a neuro stromal medium supplemented with some appropriate neurotrophic factors, have been reported to play a neuroprotective effect in the peripheral nervous system. This proves our previous studies that SKP-SCs' function to bridge sciatic nerve gap in rats. However, the function of SKP-SCs in Parkinson disease (PD) remains unknown. This study was aimed to investigate the possible neuroprotective effects of SKP-SCs in 6-OHDA-induced Parkinson's disease (PD) model. Our results showed that the treatment with SKP-SCs prevented SH-SY5Y cells from 6-OHDA-induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl-2 and Bax) and the decreased expression of active caspase-3. Furthermore, we confirmed that SKP-SCs might exert protective effects and increase the mitochondrial membrane potential (MMP) through PI3K/AKT/Bcl-2 pathway. Taken together, our results demonstrated that SKP-SCs protect against 6-OHDA-induced cytotoxicity through PI3K/AKT/Bcl-2 pathway in PD model in vitro, which provides a new theoretical basis for the treatment of PD.

The p35/CDK5 signaling is regulated by p75NTR in neuronal apoptosis after intracerebral hemorrhage.

The p75 neurotrophin receptor (p75NTR), a member of tumor necrosis factor receptor superfamily, involves in neuronal apoptosis after intracerebral hemorrhage (ICH). It has been previously demonstrated that phosphorylation of p35 is a crucial factor for fighting against the proapoptotic p25/CDK5 signaling in neuronal apoptosis. Then, in ICH models of rats and primary cortical neurons, we found that the expressions of p75NTR, p-histone H1 (the kinase activity of CDK5), p25, Fas-associated phosphatase-1 (FAP-1), and phosphorylated myocyte enhancer factor 2D (p-MEF2D) were enhanced after ICH, whereas the expression of p35-Thr(138) was attenuated. Coimmunoprecipitation analysis indicated several interactions as follows: p35/p25 and CKD5, p75NTR and p35, as well as p75NTR and FAP-1. After p75NTR or FAP-1 depletion with double-stranded RNA interference in PC12 cells, the levels of p25 and p-histone H1 were attenuated, whereas p35-Thr(138) was elevated. Considering p75NTR has no effect of dephosphorylation, our results suggested that p75NTR might promote the dephosphorylation of p35-Thr(138) via interaction with FAP-1, and the p75NTR/p35 complex upregulated p25/CDK5 signaling to facilitate the neuronal apoptosis following ICH. So, in the study, we aimed to provide a theoretical and experimental basis that p75NTR could be regulated to reduce neuronal apoptosis following ICH for potential clinical treatment.

Cab45s inhibits neuronal apoptosis following intracerebral hemorrhage in adult rats.

Recent studies have shown that Cab45s, belonging to the CREC family, can fight against apoptosis in the cancer cell lines. Here, we report that Cab45s may involve in neuronal apoptosis at the early stage of intracerebral hemorrhage (ICH) in pathophysiology. We found that expression of Cab45s was enhanced in areas contiguous to hematoma following ICH in adult rats, and that so were the expressions of Glucose-regulated protein 78 (GRP78), pro-apoptotic Bcl-2-associated X protein (Bax) and active caspase-3. In vitro, coimmunoprecipitation analysis indicated the interaction between Cab45s and GRP78. Depletion of Cab45s attenuated the expression of GRP78, but increased the expressions of Bax and caspase-3 in PC12 cells treated with hemin, which finally promoted apoptosis. Together, these results reveal that Cab45s might exert its anti-apoptotic function against neuronal apoptosis. Thus, the study may provide evidences for regulating Cab45s as a potentially reliable treatment for the secondary damage following ICH.

Heart rate variability after endovascular coiling is associated with short-term outcomes in patients with subarachnoid hemorrhage.

OBJECTIVE: to evaluate whether postoperative heart rate variability (HRV) predicts short-term outcomes in patients undergoing coil embolization of ruptured aneurysms. METHODS: Consecutive patients receiving endovascular coiling to treat aneurysmal subarachnoid hemorrhage (SAH) were retrospectively reviewed between November 2011 and December 2014 in the authors' institution. Heart rate (HR) and blood pressure (BP) recorded in the initial 24 h after endovascular treatment were extracted along with other clinical data. HR variability (HRV) and BP variability (BPV) were determined as standard deviation (SD) and successive variation (SV) of every 2-h HR and BP. The correlation between HRV and clinical outcomes as assessed by Glasgow Outcome Scale (GOS) scores at discharge were analyzed statistically. RESULTS: Compared to the 310 patients with favorable outcomes (GOS 4-5), the 35 with unfavorable outcomes (GOS 1-3) had significantly higher HR, HRV, and BPV in the first postoperative day. Furthermore, HRV-SD remained to be an independent predictor of unfavorable recovery in multivariate logistic analysis (OR = 1.14; 95% CI, 1.02-1.29; P = 0.026) after adjusting for age, postoperative fever, and Glasgow Coma Scale scores on admission, which have been identified as predictors of poor prognosis. The area under the receiver operating characteristic curves for HRV-SD and BPV-SV were found to be 0.745 (95% CI, 0.658-0.833) and 0.633 (95% CI, 0.524-0.741), respectively (P < 0.05). CONCLUSIONS: Higher HRV in the first day after coil embolization was associated with unfavorable outcomes in patients with SAH. Early detection and appropriate treatment of the overactive sympathetic activity might promote functional recovery after SAH. Abbreviation: BP: Blood pressure; CI: Confidence interval; DBP: Diastolic blood pressure; GCS: Glasgow coma scale; GOS: Glasgow outcome scale; HR: Heart rate; HRV: Heart rate variability; OR: Odds ratio; ROC: Receiver operating characteristics; SD: Standard deviation; SAH: Subarachnoid hemorrhage; SV: Successive variation; SBP: Systolic blood pressure.

Postoperative blood pressure variability exerts an influence on clinical outcome after coil embolization of ruptured intracranial aneurysms.

OBJECTIVE: The present study was conducted to evaluate the effect of postoperative blood pressure (BP) variability on functional outcome in patients after coil embolization of ruptured aneurysms. METHODS: The authors retrospectively reviewed their database of patients undergoing endovascular coiling to treat subarachnoid hemorrhage (SAH) between November 2011 and December 2014. BP values were recorded every 2 hours in the initial 24 hours after endovascular obliteration of ruptured aneurysms. BP variability was determined as standard deviation (SD) and successive variation (SV). Clinical outcome at discharge was assessed by the modified Rankin Scale (mRS) and Glasgow Coma Scale (GCS) Score. BP variability obtained were correlated to patient outcome and analyzed statistically. RESULTS: Favorable outcomes (mRS 0-1) achieved in 308 (83.7%) of the 368 patients. On univariate logistic analysis, postoperative systolic blood pressure variability (SBPV)-SD, SBPV-SV, diastolic blood pressure variability (DBPV)-SD and DBPV-SV were associated with clinical outcome at discharge. SBPV-SV remained to be an independent predictor for functional recovery (OR, 0.93; 95% CI, 0.88-0.98; P = 0.009) after adjusting for age, postoperative fever, and Hunt-Hess grade by multivariate analysis. Furthermore, patients with higher SBPV had lower GCS grade at discharge (P < 0.001). There was no association between clinical outcome and mean systolic BP (SBP) (P = 0.360) or mean diastolic BP (DBP) (P = 0.105) after coiling. CONCLUSION: Postoperative SBPV was a strong predictor of clinical outcome in patients undergoing coil embolization of aneurysms, independent of mean SBP or DBP and seemed to be a potential therapeutic target in aneurysmal SAH.

Characteristics of Blood Pressure Profiles After Endovascular Coiling as Predictors of Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Accurate identification of patients who will achieve a favorable outcome is almost impossible preoperatively or postoperatively in poor-grade (Hunt and Hess Grade IV and V) aneurysmal subarachnoid hemorrhage (SAH). Whether characteristics of blood pressure profiles during the first 24 hours after endovascular coiling could predict prognosis in poor grade patients was explored. METHODS: Data were obtained retrospectively on all patients undergoing endovascular treatment with poor-grade SAH from November 2011 to June 2016. Blood pressure during the initial 24 hours was measured at 2-hour intervals after coil embolization. Studied features of mean systolic blood pressure (MSBP) and systolic blood pressure variability (SBPV) as well as demographics, medical history, clinical characteristics, and neurologic outcomes were documented. SBPV was determined as standard deviation and successive variation of systolic blood pressure. Logistic regression analysis was used to identify predictors of favorable outcome assessed on modified Rankin Scale score of 0 to 2. RESULTS: The patients with favorable and unfavorable outcome were comparable with respect to systolic blood pressure on admission and MSBP after coiling. However, MSBP between 120 and 140 mm Hg was one of independent predictors of good outcomes at discharge (odds ratio 7.1; P = 0.002). SBPV-successive variation after embolization was associated with functional recovery (odds ratio 0.87; P = 0.011) in multivariate logistic analysis and mortality by Cox proportional hazard regression (hazard ratio, 1.10; P = 0.001) at 6-month follow-up. CONCLUSIONS: Characteristics of blood pressure profiles after coiling appeared to be simple and convenient indexes for the prognosis of patients with poor-grade SAH.

Association of Different Stenting Procedures with Symptomatic Thromboembolic Complications in Stent-Assisted Coiling of Ruptured Wide-Necked Intracranial Aneurysms.

OBJECTIVE: This study aimed to evaluate the association of different stenting procedures with the procedure-related complications in stent-assisted coiling (SAC) of ruptured wide-necked aneurysms. METHODS: Consecutive patients undergoing SAC of ruptured wide-necked aneurysms were retrospectively reviewed between December 2011 and June 2016. They received 1 of the 3 stenting procedures during SAC: 1) the coiling microcatheter was "jailed" outside of the stent and the coil embolization proceeded above the stent; 2) initial stent deployment followed by the coils through the stent's strut technique; or 3) the coil-then-stent technique. The effect of different stenting procedures on clinical complications and outcomes was estimated by logistic regression models. RESULTS: Of the 93 patients enrolled in this study, 11 of them (11.8%) suffered from symptomatic thromboembolic events and 10 of them (10.8%) had hemorrhagic complications. SAC with different stenting procedures (odds ratio [OR] = 4.10, 95% confidence interval [CI]: 1.20-13.97, P = 0.024) was the only independent risk factor for symptomatic thromboembolic events. The coil-then-stent technique had a higher ischemic complications rate than the other 2 stenting procedures (P = 0.023). Serum glucose (OR = 1.48, P = 0.014) and systolic blood pressure on admission (OR = 0.97, P = 0.046) were independent predictors of hemorrhagic complications during SAC. However, different stenting procedures and stent types were correlated with neither aneurysm occlusion at the end of procedure (P = 0.498 and 0.176, respectively) nor favorable outcome at discharge (P = 0.710 and 0.928, respectively). CONCLUSION: Different stenting procedures were associated with thromboembolic but not hemorrhagic complications in SAC of ruptured wide-necked aneurysms.

Up-Regulation of TAB3 Is Involved in Neuronal Apoptosis After Intracerebral Hemorrhage.

Human transforming growth factor ß-activated kinase (TAK1)-binding protein 3 (TAB3) is a regulator of NF-κB which has been mainly found in a variety of cancers. While TAB3 is highly expressed in brain tissue, little is known about the function of TAB3 in central nervous system. Our group established an animal ICH model with autologous whole blood injected into brain, and also a cell ICH model with hemin stimulation. Our Western blot result showed up-regulation of TAB3 during neuronal apoptosis in the model of intracerebral hemorrhage (ICH), which was also approved by immunofluorescence and immunohistochemistry result. Besides, increasing TAB3 level was accompanied by the increased expression of active-caspase-3, active-caspase-8, and decreased expression of Bcl-2. Furthermore, in in vitro study, the level of neuronal apoptosis was decreased by applying TAB3- RNA interference in PC12 cells. All the results above suggested that TAB3 probably participates in the process of neuronal apoptosis following ICH.

Investigation of Long Non-coding RNA Expression Profiles in the Substantia Nigra of Parkinson's Disease.

Genetics is considered as an important risk factor in the pathological changes of Parkinson's disease (PD). Substantia nigra (SN) is thought to be the most vulnerable area in this process. In recent decades, however, few related long non-coding RNAs (lncRNAs) in the SN of PD patients had been identified and the functions of those lncRNAs had been studied even less. In this study, we sought to investigate the lncRNA expression profiles and their potential functions in the SN of PD patients. We screened lncRNA expression profiles in the SN of PD patients using the lncRNA mining approach from the ArrayExpress database, which included GSE20295. The samples were from 11 of PD and 14 of normal tissue samples. We identified 87 lncRNAs that were altered significantly in the SN during the occurrence of PD. Among these lncRNAs, lncRNA AL049437 and lncRNA AK021630 varied most dramatically. AL049437 was up-regulated in the PD samples, while AK021630 was down-regulated. Based on the results, we focused on the potential roles of the two lncRNAs in the pathogenesis of PD by the knockdown of the expression of AL049437 or AK021630 in human neuroblastoma SH-SY5Y cell line. Results indicated that the reduction in AL049437 level increased cell viability, mitochondrial transmembrane potential (Δψm), mitochondrial mass, and tyrosine hydroxylase (TyrH) secretion. By contrast, the knockdown of AK021630 resulted in the opposite effect. Based on these results, we speculated that lncRNA AL049437 likely contributed to the risk of PD, while lncRNA AK021630 likely inhibited the occurrence of PD.

OTUB1 attenuates neuronal apoptosis after intracerebral hemorrhage.

OTUB1 is a member of deubiquitinating enzymes, which was shown as a proteasome-associated DUB to be involved in the proteins Ub-dependent degradation. Previous studies have indicated that OTUB1 was expressed in brain. But its distribution and function in the brain remain unclear. In this study, we explored the roles of OTUB1 protein in the pathophysiology of intracerebral hemorrhage (ICH). From the results of Western blot, immunohistochemistry, and immunofluorescence, we found an obvious up-regulation of OTUB1 in neurons adjacent to the hematoma after ICH. Furthermore, we also found that the increase of OTUB1 expression was accompanied by the enhanced expression of Bax and active caspase-3, and decreased expression of Bcl-2 in the pathological process of rat ICH. What's more, our in vitro study, using OTUB1 RNA interference in PC12 cells, suggested that OTUB1 might exert its anti-apoptotic function in neuronal apoptosis. Therefore, OTUB1 may play a role in protecting the brain from secondary damage following ICH.

Upregulation of PRDM5 Is Associated with Astrocyte Proliferation and Neuronal Apoptosis Caused by Lipopolysaccharide.

PRDM5 (PR domain containing 5) belongs to PRDM family which consists of transcriptional regulators that modulate cellular processes such as cell growth, differentiation and apoptosis. However, the function of PRDM5 in central nervous system (CNS) inflammatory response is unknown. In recent study, an adult rat neuroinflammation model via lipopolysaccharide (LPS) lateral ventricle injection was constructed. PRDM5 expression was increased in activated astrocytes and apoptotic neurons of the adult rat cerebral cortex after LPS injection. In vitro studies showed that the remarkable upregulation of PRDM5 might be involved in rat primary astrocyte proliferation and rat primary neuronal apoptosis in the cerebral cortex following LPS administration. In addition, using PRDM5 RNA interference both in rat primary asrtocytes and neurons, further indicated that PRDM5 was required for astrocyte proliferation and neuronal apoptosis induced by LPS. Our findings on the cellular signaling pathway may provide a new therapeutic strategy against neuroinflammation in the CNS.