The role of neuroinfammation in glaucoma

Glaucoma is a chronic neurodegener-ative disorder characterized by progressive damage and loss of retinal ganglion cells （RGCs）. It is considered one of the leading causes of irreversible blindness in the older population. There are estimates that glaucoma will affect 80 million individuals worldwide by the end of this de-cade, and yet we are still not able to identify the signals and the mechanisms that trigger this neurodegenerative disease. Various hypotheses have been generated to ad-dress the causes of the progressive RGC death that char-acterizes the disease. Age and increased intraocular pres-sure （IOP） have been established as the main risk factors for the development of glaucoma. Recent studies have identifed additional factors that play a role in the patho-genesis of this complex multifactorial disease, including infammation, oxidative stress, vascular dysregulation, disrupted axonal transport of neurotrophic factors, and the release of neurotoxic agents such as glutamate, nitric oxide and free radicals. The currently approved therapies for glaucoma that seek to reduce IOP, including medica-tions, laser treatment, and surgery, are unable to reliably stop RGC loss and functional impairment. Considering the signifcant personal, medical and socio-economic im-pacts of glaucoma as a leading cause of blindness, there is a pressing need for new innovative treatment strategies. Here we focus on the role of neuroinfammation in glau-coma and the opportunities that new fndings in this area have for the development of future therapeutics.

Chemical exposures and suspected impacton Gulf War Veterans

Gulf War Illness(GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not limited to)exposures to chemical agents and a foreign environment(e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants,may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure.

Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease

The accumulation of pathological α-synuclein(α-syn)in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease(PD).Recently,the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution ofα-syn in PD patients.Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells,which contributes to the clearance of α-syn.However,the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons,which promotes the spread of α-syn pathology.In this article,we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis,highlighting the relationships between glial responses and the spread ofα-syn pathology.

Interactions Between Astrocytes and Oligodendroglia in Myelin Development and Related Brain Diseases

Astrocytes(ASTs)and oligodendroglial lineage cells(OLGs)are major macroglial cells in the central nervous system.ASTs communicate with each other through connexin(Cx)and Cx-based network structures,both of which allow for quick transport of nutrients and signals.Moreover,ASTs interact with OLGs through connexin(Cx)-mediated networks to modulate various physiological processes in the brain.In this article,following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk,we focus on recapitulating how the interactions between these two types of glial cells modulate myelination,and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier(BBB)and regulating synaptogenesis and neural activity.Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases,such as multiple sclerosis.A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.

miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice

Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavailable.Here,we established a mouse model of PSD through photothrombosis-induced focal ischemia.By using a combination of brain imaging,transcriptome sequencing,and bioinformatics analysis,we found that the hippocampus of PSD mice had a signifcantly lower metabolic level than other brain regions.RNA sequencing revealed a signifcant reduction of miR34b-3p,which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E(eIF4E).Furthermore,silencing eIF4E inactivated microglia,inhibited neuroinfammation,and abolished the depression-like behaviors in PSD mice.Together,our data demonstrated that insufcient miR34b-3p after stroke cannot inhibit eIF4E translation,which causes PSD by the activation of microglia in the hippocampus.Therefore,miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.