Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)–related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS counter transport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation.Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg×2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injetions was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity.

Rationale: Eclampsia, an obstetric emergency frequently seen in pregnant or puerperal women, is a risk factor for posterior reversible encephalopathy syndrome (PRES). Most cases of eclampsia occur postpartum. We report a woman with PRES associated with eclampsia 10 weeks post-delivery, the latest onset ever reported. Patient concerns: A 23-year-old healthy woman presented headache and nausea 10 weeks after delivery. Two days later, she generalized tonic-clonic seizure. Her brain MRI presented the foci which is typical of PRES. Diagnosis: The patient was diagnosed as PRES associated with eclampsia. Interventions: The patient received levetiracetam and edaravone. Outcomes: Her clinical course was uneventful and she fully recovered without neurological complications Lessons: The possible diagnosis of late onset postpartum eclampsia, even weeks post-delivery, should be considered, since initiation of early treatment averts severe complications and decreases mortality. Sharing our experience may increase awareness of PRES induced by late-onset postpartum eclampsia.

We previously established an animal model of Parkinson's disease (PD) induced by chronic low-dose rotenone as an environmental neurotoxic pesticide that reproducible central and enteric neurodegenerative features of PD, and also found that rotenone-induced enteric neurodegeneration is caused by dysfunction of enteric glia using primary cultured enteric cells. However, the mechanism of enteric neurodegeneration and inflammation are still obscure. In this study, we examined changes in enteric cellular environment in the enteric epithelium and myenteric plexus of the rotenone-induced PD model mice. Chronic subcutaneous administration with low-dose rotenone (2.5 mg/kg/day) for 4 weeks using an osmotic mini pump reduced the number of dopamine neurons in the substantia nigra and the intestinal myenteric neurons and glial cells of mice. Furthermore, it produced disruption of mucosal epithelial barrier and marked translocation of HMGB1 to the cytosol beside nuclear membrane towards the apical lumen side. These results suggest that the rotenone-induced dysfunctions of epithelial barrier and HMGB1 transportation are involved in the inflammatory reactions and dysfunction of enteric glia and consequent enteric neurodegeneration.