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Ischemic preconditioning (IPC) is a phenomenon whereby a brief, non‐injurious ischemic exposure enhances tolerance to a subsequent ischemic challenge. The mechanism of IPC has mainly been studied in rodent stroke models where gray matter (GM) constitutes about 85% of the cerebrum. In humans, white matter (WM) is 50% of cerebral volume and is a critical component of stroke damage. We developed a novel...
Neuropathic pain is a prevalent and debilitating chronic disease that is characterized by activation in glial cells in various pain‐related regions within the central nervous system. Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to identify...
Astrocytes, the most abundant glial cells in the mammalian brain, directly associate with and regulate neuronal processes and synapses and are important regulators of brain development. Yet little is known of the molecular mechanisms that control the establishment of astrocyte morphology and the bi‐directional communication between astrocytes and neurons. Here we show that neuronal contact stimulates...
Microglia are increasingly being recognized as druggable targets in neurodegenerative disorders, and good in vitro models are crucial to address cell biological questions. Major challenges are to recapitulate the complex microglial morphology and their in vivo transcriptome. We have therefore exposed primary microglia from adult rhesus macaques to a variety of different culture conditions including...
Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)‐derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy...
Many patients with systemic lupus erythematosus (SLE) live with chronic pain despite advances in medical management in reducing mortality related to SLE. Few animal studies have addressed mechanisms and treatment for chronic pain caused by SLE. In this study, we provide the first evidence for the analgesic effects of a GPR109A specific agonist (MK1903) and its action mechanisms in thermal hyperalgesia...
Alzheimer pathology is accompanied by astrogliosis. Reactive astrocytes surrounding amyloid plaques may directly affect neuronal communication, and one of the mechanisms by which astrocytes impact neuronal function is by affecting K+ homeostasis. Here we studied, using hippocampal slices from 9‐month‐old Alzheimer mice (APP/PS1) and wild‐type littermates, whether astrocyte function is changed by analyzing...
Cover Illustration: Confocal laser scanning microscopy image of astrocytes interacting with an amyloid‐ß plaque in the middle molecular layer of the dentate gyrus in the APPswe/PSEN1dE9 mouse model for Alzheimer's disease. Astrocytes display cytoskeletal (glial fibrillary acidic protein – green) changes and enclose the Aβ plaque deposit (red). (See Huffels, CF et al, https://doi.org/10.1002/glia.24137...
The auditory nerve (AN) of the inner ear is the primary conveyor of acoustic information from sensory hair cells to the brainstem. Approximately 95% of peripheral AN fibers are myelinated by glial cells. The integrity of myelin and the glial‐associated paranodal structures at the node of Ranvier is critical for normal AN activity and axonal survival and function in the central auditory nervous system...
Microglial cells (MGCs) are highly dynamic and have been implicated in shaping discrete neural maps in several unimodal systems. MGCs respond to numerous cues in their microenvironment, including the neuronally expressed chemokine, fractalkine (CX3CL1), via interactions with its corresponding fractalkine receptor (CX3CR1). The present study examines microglial and CX3CL1 patterns with regard to the...
Stressful environmental events in early life have long‐lasting consequences on later stress responses. We previously showed that heat conditioning of 3‐day‐old chicks during the critical period of heat‐response development leads to heat vulnerability later in life. Here we assessed the role of early‐life heat stress on the inflammatory response in the chick anterior hypothalamus (AH), focusing on...
A major challenge for studying neuron‐astrocyte communication lies in visualizing the tripartite synapse, which is the physical site where astrocytic processes contact and interact with neuronal synapses. While conventional light microscopy cannot resolve the anatomical details of the tripartite synapse, electron microscopy only provides ultrastructural snapshots that tell us little about its living...
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