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Inflammatory responses mediated by glial cells play a critical role in many pathological situations related to neurodegeneration such as Alzheimer's disease. Tissue plasminogen activator (tPA) is a serine protease which best‐known function is fibrinolysis, but it is also involved in many other physiological and pathological events as microglial activation. Here, we found that tPA is required for Aβ‐mediated...
Activation and proliferation of glial cells and their progenitors is a key process of neuroinflammation associated with many neurodegenerative disorders. Under neuropathological conditions where glial cell activation and proliferation is evident, controlling the population of glia might be of therapeutic importance. The proliferative action of the cytokine tumor necrosis factor alpha (TNFα) on microglia...
Uptake of K+ released by axons during action potential propagation is a major function of astrocytes. Here, we demonstrate the importance of glial inward rectifying potassium channels (Kir) in regulating extracellular K+ ([K+]o) and axonal electrical activity in CNS white matter of the mouse optic nerve. Increasing optic nerve stimulation frequency from 1 Hz to 10–35 Hz for 120 s resulted in a rise...
Schwann cells (SCs) are crucial for peripheral nerve development and regeneration; however, the intrinsic regulatory mechanisms governing postinjury responses are poorly understood. Activation and deacetylation of nuclear factor‐κB (NF‐ κB) in SCs have been implicated as prerequisites for peripheral nerve myelination. Using GFAP‐IκBα‐dn mice in which NF‐ κB transcriptional activation is inhibited...
Neuronal activity is accompanied by a rapid increase in interstitial lactate, which is hypothesized to serve as a fuel for neurons and a signal for local vasodilation. Using FRET microscopy, we report here that the rate of glycolysis in cultured mice astrocytes can be acutely modulated by physiological changes in extracellular lactate. Glycolytic inhibition by lactate was not accompanied by detectable...
Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age‐related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular...
Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll‐like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes...
Rab4 and Rab5 GTPases are key players in the regulation of endocytosis. Although their role has been studied intensively in the past, it is still unclear how they regulate vesicle mobility. In particular, in astrocytes, the most abundant glial cells in the brain, vesicles have been shown to exhibit nondirectional and directional mobility, which can be intermittent, but the underlying switching mechanisms...
Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired‐pulse plasticity of synaptically activated, glutamate transporter‐mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs...
We analyzed cell cycle‐associated proteins, including cyclins, cyclin‐dependent protein kinases (Cdks), and Cdk inhibitors (CdkIs) in the axotomized rat facial nucleus. Immunoblotting revealed that cyclin A and cyclin D are induced 3–5 days after transection. The induced cyclin A was immunohistochemically recognized in microglia. Cdk2 and Cdk4 were also detected in the facial nucleus. The CdkI p21...
The ϵ4 allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for late‐onset Alzheimer's disease (AD), and affects clinical outcomes of chronic and acute brain damages. The mechanisms by which apoE affect diverse diseases and disorders may involve modulation of the glial response to various types of brain damage. We examined glial activation in a mouse model where each of...
Emerging evidence suggests that p53, a tumor suppressor protein primarily involved in cancer biology, coordinates a wide range of novel functions in the CNS including the mediation of pathways underlying neurodegenerative disease pathogenesis. Moreover, an evolving concept in cell and molecular neuroscience is that glial cells are far more fundamental to disease progression than previously thought,...
Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 transgenic (AD) mice at different ages. Mice were studied shortly after the last BrdU...
Formaldehyde is a neurotoxic compound that can be endogenously generated in the brain. Because astrocytes play a key role in metabolism and detoxification processes in brain, we have investigated the capacity of these cells to metabolize formaldehyde using primary astrocyte‐rich cultures as a model system. Application of formaldehyde to these cultures resulted in the appearance of formate in cells...
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