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The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1−/− (26.42 ± 7...
Accumulative evidence indicates that microglial cells influence the normal development of central nervous system (CNS) synapses. Yet, the functional properties of microglia in relation with synapse development remain unclear. We recently showed that in layer 4 of the whisker‐related barrel field of the mouse somatosensory cortex, microglial cells are recruited only after postnatal day (P)5 in the...
Neuroinflammation underlies a wide variety of pathological processes in the central nerve system (CNS). Although previous experimental and clinical studies indicate that activation of neuroinflammatory signaling occurs early in glaucoma, the mechanisms controlling microglia activation are still poorly defined. In the present study, we investigated the role of the chemokine receptor Cx3cr1 in microglia...
Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia...
Microglia have recently been implicated as key regulators of activity‐dependent plasticity, where they contribute to the removal of inappropriate or excess synapses. However, the molecular mechanisms that mediate this microglial function are still not well understood. Although multiple studies have implicated fractalkine signaling as a mediator of microglia–neuron communications during synaptic plasticity,...
Deficient neuron–microglia signaling during brain development is associated with abnormal synaptic maturation. However, the precise impact of deficient microglia function on synaptic maturation and the mechanisms involved remain poorly defined. Here we report that mice defective in neuron‐to‐microglia signaling via the fractalkine receptor (Cx3cr1 KO) show reduced microglial branching and altered...
Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)‐to‐Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning‐relevant processes during early postnatal development. Until now, the role of microglia in pruning remains under intense investigation...
Microglial activation has been regarded mainly as an exacerbator of stress response, a common symptom in psychiatric disorders. This study aimed to determine whether microglia contribute to adaptive response of the brain and behavior toward stress using a mild and adaptive stress model – chronic restraint stress (CRS) – with wild type (WT) and CX3CR1‐GFP (CX3CR1[G]) mice and human schizophrenia patients'...
Microglia, the brain's resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases...
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...
Neuron–microglia communication through the Cx3cr1–Cx3cl1 axis is essential for the development and refinement of neural circuits, which determine their function into adulthood. In the present work we set out to extend the behavioral characterization of Cx3cr1−/− mice evaluating innate behaviors and spatial navigation, both dependent on hippocampal function. Our results show that Cx3cr1‐deficient mice,...
Fractalkine (FKN) is a membrane‐bound chemokine that can be cleaved by proteases such as ADAM 10, ADAM 17, and cathepsin S to generate soluble fragments. Studies using different forms of the soluble FKN yield conflicting results in vivo. These observations prompted us to investigate the function and pharmacology of two commonly used isoforms of FKN, a human full‐length soluble FKN (sFKN), and a human...
Synucleinopathies refer to a range of neurodegenerative diseases caused by abnormal α‐synuclein (α‐Syn) deposition, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Their pathogenesis is strongly linked to microglial dysfunction and neuroinflammation, which involves the leucine‐rich‐repeat kinase 2 (LRRK2)‐regulated nuclear factor of activated...
Nogo‐A, B, and C are well described members of the reticulon family of proteins, most well known for their negative regulatory effects on central nervous system (CNS) neurite outgrowth and repair following injury. Recent research indicates a relationship between Nogo‐proteins and inflammation. Microglia, the brain's immune cells and inflammation‐competent compartment, express Nogo protein, although...
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...
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