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Cover Illustration: Confocal image of a mature oligodendrocyte in vitro following the addition of netrin‐1, immuno‐labelled for the mitochondrial docking protein syntaphilin (red), the outer mitochondrial membrane protein TOM20 (green), myelin basic protein (white), and Hoechst dye (blue). Syntaphilin is associated with mitochondria in mature oligodendrocytes and recruited to cell processes by netrin‐1...
Triggering receptor expressed on myeloid cell 2 (TREM2), a myeloid cell‐specific signaling molecule, controls essential functions of microglia and impacts on the pathogenesis of Alzheimer's disease and other neurodegenerative disorders. TREM2 is also highly expressed in tumor‐associated macrophages in different types of cancer. Here, we studied whether TREM2 influences glioma progression. We found...
The adult zebrafish brain, unlike mammals, has a remarkable regenerative capacity. Although inflammation in part hinders regeneration in mammals, it is necessary for zebrafish brain repair. Microglia are resident brain immune cells that regulate the inflammatory response. To explore the microglial role in repair, we used liposomal clodronate or colony stimulating factor‐1 receptor (csf1r) inhibitor...
Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels...
Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non‐neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It...
Mutations leading to colony‐stimulating factor‐1 receptor (CSF‐1R) loss‐of‐function or haploinsufficiency cause CSF1R‐related leukoencephalopathy (CRL), an adult‐onset disease characterized by loss of myelin and neurodegeneration, for which there is no effective therapy. Symptom onset usually occurs in the fourth decade of life and the penetrance of disease in carriers is high. However, familial studies...
Gamma‐aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, affects numerous immune cell functions. Microglia, the brain's resident innate immune cells, regulate GABA signaling through GABA receptors and express the complete GABAergic machinery for GABA synthesis, uptake, and release. Here, the use of primary microglial cell cultures and ex vivo brain tissue sections allowed...
Circadian oscillators, defined by cellular 24 h clock gene rhythms, are found throughout the brain. Cerebral cortex‐specific conditional knockout of the clock gene Bmal1 (Bmal1 CKO) leads to depressive‐like behavior, but the molecular link from clock gene to altered behavior is unknown. Further, diurnal proteomic data on the cerebral cortex are currently unavailable. With the aim of determining the...
Resident microglia are important to maintain homeostasis in the central nervous system, which includes the retina. The retinal microglia become activated in numerous pathological conditions, but the molecular signatures of these changes are poorly understood. Here, using an approach based on FACS and RNA‐seq, we show that microglial gene expression patterns gradually change during RGC degeneration...
Brain edema is a feared complication to disorders and insults affecting the brain. It can be fatal if the increase in intracranial pressure is sufficiently large to cause brain herniation. Moreover, accruing evidence suggests that even slight elevations of intracranial pressure have adverse effects, for instance on brain perfusion. The water channel aquaporin‐4 (AQP4), densely expressed in perivascular...
Demyelination in the central nervous system (CNS) is a hallmark of many neurodegenerative diseases such as multiple sclerosis (MS) and others. Here, we studied astrocytes during de‐ and remyelination in the cuprizone mouse model. To this end, we exploited the ribosomal tagging (RiboTag) technology that is based on Cre‐mediated cell type‐selective HA‐tagging of ribosomes. Analyses were performed in...
The expressions of ion channels by Müller glial cells (MGCs) may change in response to various retinal pathophysiological conditions. There remains a gap in our understanding of MGCs' responses to photoreceptor degeneration towards finding therapies. The study explores how an inhibition of store‐operated Ca2+ entry (SOCE) and its major component, Orai1 channel, in MGCs protects photoreceptors from...
In the central nervous system, oligodendrocytes (OLs) produce myelin sheaths that provide trophic support to neuronal axons and increase the propagation speed of action potential. OLs are constantly generated from OL precursor cells (OPCs) throughout life span. The production of myelinating OLs consists of three canonical stages: OPCs, newly‐formed OLs (NFOs), and mature myelinating OLs. Recently,...
Cover Illustration: Confocal microscope image of an immunohistochemical staining of the hippocampal dentate gyrus of a cerebral cortex‐specific circadian clock gene Bmal1 conditional knockout mouse. The image illustrates the resulting increased density and intensity of the astrocytic marker GFAP (green) here combined with a DAPI nuclear stain (blue). (See Bering, T., et al. https://doi.org/10.1002/glia...
The zebrafish retina possesses tremendous regenerative potential. Müller glia underlie retinal regeneration through their ability to reprogram and generate multipotent neuronal progenitors that re‐differentiate into lost neurons. Many factors required for Müller glia reprogramming and proliferation have been identified; however, we know little about the epigenetic and transcriptional regulation of...
Microglia, the major immune cells of the brain, are functionally heterogeneous but in vivo functional properties of these cells are rarely studied at single‐cell resolution. By using microRNA‐9 regulated viral vectors for multicolor labeling and longitudinal in vivo monitoring of individual microglia, we followed their fate in the cortex of healthy adult mice and at the onset of amyloidosis in a mouse...
Zinc finger protein 335 (Zfp335) is a transcription factor that regulates mammalian neurogenesis and neuronal differentiation. It is a causative factor for severe microcephaly, small somatic size, and neonatal death. Here, we evaluated the effects of Zfp335 in the adult mouse brain after lipopolysaccharide (LPS) challenge. We used wild‐type (WT) and Zfp335 knock‐down (Zfp335+/−) mice with LPS administered...
Parkinson's disease (PD) is a common neurodegenerative disease in elderly people, which is characterized by motor disabilities in PD patients. Nav1.6 is the most abundant subtype of voltage‐gated sodium channels (VGSCs) in the brain of adult mammals and rodents. Here we investigated the role of Nav1.6 in the external globus pallidus (GP) involved in the pathogenesis of motor deficits in unilateral...