CX3 chemokine receptor 1 defciency leads to reduced dendritic complexity and delayed maturation of newborn neurons in the adult mouse hippocampus

Feng, Xiao; Xu, Junmei; Jiang, Xinghua

doi:10.4103/1673-5374.156979

Cited by 24 publications

(13 citation statements)

References 37 publications

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“…To further examine the role of microglia in obesity-induced cognitive decline, we used transgenic Cx3cr1 ϩ/Ϫ mice, in which one allele of Cx3cr1 is replaced with the gene for GFP (Jung et al, 2000). We decided to use heterozygous Cx3Cr1 ϩ/Ϫ instead of homozygous Cx3Cr1 Ϫ/Ϫ mice because greater abnormalities in hippocampal structure and cognitive behavior have been observed with the complete knock-out (Rogers et al, 2011;Xiao et al, 2015;Sellner et al, 2016). Consistent with what we observed for WT mice, adult Cx3cr1 ϩ/Ϫ mice fed HFD for 12 weeks were significantly heavier than control-fed Cx3cr1 ϩ/Ϫ mice (Fig.…”

Section: Hfd Induces Obesity In Cx3cr1-deficient Micementioning

confidence: 99%

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

et al. 2018

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Obesity affects >600 million people worldwide, a staggering number that appears to be on the rise. One of the lesser known consequences of obesity is its deleterious effects on cognition, which have been well documented across many cognitive domains and age groups. To investigate the cellular mechanisms that underlie obesity-associated cognitive decline, we used diet-induced obesity in male mice and found memory impairments along with reductions in dendritic spines, sites of excitatory synapses, increases in the activation of microglia, the brain's resident immune cells, and increases in synaptic profiles within microglia, in the hippocampus, a brain region linked to cognition. We found that partial knockdown of the receptor for fractalkine, a chemokine that can serve as a "find me" cue for microglia, prevented microglial activation and cognitive decline induced by obesity. Furthermore, we found that pharmacological inhibition of microglial activation in obese mice was associated with prevention of both dendritic spine loss and cognitive degradation. Finally, we observed that pharmacological blockade of microglial phagocytosis lessened obesity-associated cognitive decline. These findings suggest that microglia play an active role in obesity-associated cognitive decline by phagocytosis of synapses that are important for optimal function. Obesity in humans correlates with reduced cognitive function. To investigate the cellular mechanisms underlying this, we used diet-induced obesity in mice and found impaired performance on cognitive tests of hippocampal function. These deficits were accompanied by reduced numbers of dendritic spines, increased microglial activation, and increased synaptic profiles within microglia. Inhibition of microglial activation by transgenic and pharmacological methods prevented cognitive decline and dendritic spine loss in obese mice. Moreover, pharmacological inhibition of the phagocytic activity of microglia was also sufficient to prevent cognitive degradation. This work suggests that microglia may be responsible for obesity-associated cognitive decline and dendritic spine loss.

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Section: Hfd Induces Obesity In Cx3cr1-deficient Micementioning

confidence: 99%

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

et al. 2018

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“…Independently of its actions on microglia, IL-34 can also activatetheCSF-1R expressed on capillary endothelial cells and restore BBB integrity by upregulating tight junction proteins [99]. The roles of microglia in neuronal development are based on [35,57,87–90,92,94–97]. Abbreviations: Cb, cerebellum; CC, corpuscallosum; Cx, cortex; Hp, hippocampus; MΦ, macrophage; M1–M3 denote microglial activation states with M1 representing inflammatory microglia; M2, alternatively activated, trophic microglia; and M3 rapidly proliferating microglia that are not M1-or M2- polarized; NB, neuroblast; OB, olfactorybulb; RMS, rostral migratory stream; St, striatum; SVZ, subventricular zone; YS, yolk sac.…”

Section: Figurementioning

confidence: 99%

Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

Chiţu

Gökhan

Nandi

et al. 2016

Trends in Neurosciences

267

227

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The colony stimulating factor-1 receptor (CSF-1R) kinase regulates tissue macrophage homeostasis, osteoclastogenesis, and Paneth cell development. However, recent studies in mice have revealed that CSF-1R signaling directly controls the development and maintenance of microglia, and cell autonomously regulates neuronal differentiation and survival. While the CSF-1R-cognate ligands, CSF-1 and interleukin-34 (IL-34), compete for binding to the CSF-1R, they are expressed in a largely non-overlapping manner by mature neurons. The recent identification of a dominantly inherited, adult-onset, progressive dementia associated with inactivating mutations in the CSF-1R highlights the importance of CSF-1R signaling in the brain. We review the roles of the CSF-1R and its ligands in microglial and neural development and function, and their relevance to our understanding of neurodegenerative disease.

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“…Indeed, fractalkine signaling was shown to regulate learning and memory (Maggi et al, 2011), social behaviors (Zhan et al, 2014), and microglial neurotoxicity during inflammation and stroke (Cardona et al, 2006; Tang et al, 2014). Under epileptic conditions, recent studies found that fractalkine deficiency resulted in reduced dendritic complexity and delayed maturation of adult newborn neurons (Xiao et al, 2015). However, the exact role of fractalkine signaling in seizure-induced microglia–neuron physical interactions has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Physical Microglia–Neuron Interactions by Fractalkine Signaling after Status Epilepticus

Eyo

Peng

Murugan

et al. 2016

eNeuro

108

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Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia–neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid– or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia–neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1–CX3CR1 communication axis as a modulator of potentially neuroprotective microglia–neuron physical interactions during conditions of neuronal hyperactivity.

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CX3 chemokine receptor 1 defciency leads to reduced dendritic complexity and delayed maturation of newborn neurons in the adult mouse hippocampus

Cited by 24 publications

References 37 publications

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

Regulation of Physical Microglia–Neuron Interactions by Fractalkine Signaling after Status Epilepticus

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