Using transmission electron microscopy (TEM) we recently characterized a microglial phenotype that is induced by chronic stress, fractalkine receptor deficiency, aging, or Alzheimer disease pathology. These 'dark' microglia appear overly active compared with the normal microglia, reaching for synaptic clefts, and extensively engulfing pre-synaptic axon terminals and post-synaptic dendritic spines. From these findings we hypothesized that dark microglia could be specifically implicated in the pathological remodeling of neuronal circuits, which impairs learning, memory, and other essential cognitive functions. In the present addendum we further discuss about the possible causes of their dark appearance under TEM.
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http://dx.doi.org/10.1080/19420889.2016.1230575 | DOI Listing |
Front Physiol
January 2025
Departamento de Anatomía, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Introduction: Access to electric light has exposed living organisms to varying intensities of light throughout the 24 h day. Dim light at night (DLAN) is an inappropriate signal for the biological clock, which is responsible for the circadian organization of physiology. During the gestational period, physiological adaptations occur to ensure a successful pregnancy and optimal fetal development.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Department of Neuroscience and Experimental Therapeutics, School of Medicine, Texas A&M Health Science Center, Bryan, TX, 77807-3260, USA.
Background: Disturbances of the sleep-wake cycle and other circadian rhythms typically precede the age-related deficits in learning and memory, suggesting that these alterations in circadian timekeeping may contribute to the progressive cognitive decline during aging. The present study examined the role of immune cell activation and inflammation in the link between circadian rhythm dysregulation and cognitive impairment in aging.
Methods: C57Bl/6J mice were exposed to shifted light-dark (LD) cycles (12 h advance/5d) during early adulthood (from ≈ 4-6mo) or continuously to a "fixed" LD12:12 schedule.
Alcohol
February 2025
Department of Psychiatry, Yale University, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Stress is a major contributing factor to binge drinking and development of alcohol use disorders (AUD), particularly in women. Both stress and chronic ethanol can enhance neuroinflammatory processes, which may dysregulate limbic circuits involved in ethanol reinforcement. Clinical and preclinical studies have identified sex differences in alcohol intake in response to neuroinflammatory triggers.
View Article and Find Full Text PDFBrain Struct Funct
December 2024
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Microglia play important roles in maintaining homeostasis and immunoreactive defense in the central nervous system including retina. To accomplish such a wide range of functions, microglia are highly heterogeneous. Dark microglia (DM) were recently identified by electron microscopy (EM).
View Article and Find Full Text PDFNeuron
December 2024
Neuroscience Initiative, Advanced Science Research Center, The City University of New York (CUNY) Graduate Center, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA; Graduate Program in Biochemistry, CUNY Graduate Center, New York, NY 10016, USA. Electronic address:
The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes.
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