Microglial regulation of satiety and cognition

Luca, Simone N. De; Miller, Alyson A.; Sominsky, Luba; Spencer, Sarah J.

doi:10.1111/jne.12838

Cited by 22 publications

(19 citation statements)

References 121 publications

(304 reference statements)

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“…In addition, microglia depletion by diphtheria toxin was not associated with any evidence of impairment in learning and memory as measured by short-term memory in a novel object and place recognition tasks [16]. Further studies indicate that the anorexia induced by administration of diphtheria toxin to Cx3cr1-Dtr rats is actually due to disruption of the gustatory circuitry a the level of the paraventricular nucleus of the hypothalamus [15], indicating the complex role microglia play in brain functions additional to their traditional role in regulating neuroinflammation [24].…”

Section: Discussionmentioning

confidence: 89%

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Vichaya

Malik

Sominsky

et al. 2020

J Neuroinflammation

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Background: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation. Methods: Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonist of colony stimulating factor-1 receptor, and in rats by a knock-in model in which the diphtheria toxin receptor was expressed under the control of the endogenous fractalkine receptor (CX3CR1) promoter sequence. After successful microglia depletion, mice and rats were injected with a sickness-inducing dose of lipopolysaccharide according to a 2 (depletion vs. control) × 2 (LPS vs. saline) factorial design. Sickness was measured by body weight loss and decreased locomotor activity in rats and mice, and reduced voluntary wheel running in mice. Results: Chronic administration of PLX5622 in mice and administration of diphtheria toxin to knock-in rats depleted microglia and peripheral tissue macrophages. However, it did not abrogate the inducible expression of proinflammatory cytokines in the brain in response to LPS and even exacerbated it for some of the cytokines. In accordance with these neuroimmune effects, LPS-induced sickness was not abrogated, rather it was exacerbated when measured by running wheel activity in mice. Conclusions: These findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.

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Section: Discussionmentioning

confidence: 89%

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Vichaya

Malik

Sominsky

et al. 2020

J Neuroinflammation

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“…In addition, microglia depletion by diphtheria toxin was not associated with any evidence of impairment in learning and memory as measured by short term memory in a novel object and place recognition tasks (16). Further studies indicate that the anorexia induced by administration of diphtheria toxin to Cx3cr1-Dtr rats is actually due to disruption of the gustatory circuitry a the level of the paraventricular nucleus of the hypothalamus (15), indicating the complex role microglia play in brain functions additional to their traditional role in regulating neuroinflammation (22).…”

Section: Discussionmentioning

confidence: 89%

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Vichaya

Malik

Sominsky

et al. 2020

Preprint

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Background: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation.Methods: Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonist of colony stimulating factor-1 receptor, and in rats by a knock-in model in which the diphtheria toxin receptor was expressed under the control of the endogenous fractalkine receptor (CX3CR1) promoter sequence. After successful microglia depletion, mice and rats were injected with a sickness-inducing dose of lipopolysaccharide according to a 2 (depletion versus control) x 2 (LPS versus saline) factorial design. Sickness was measured by body weight loss and decreased locomotor activity in rats and mice, and reduced voluntary wheel running in mice. Results: Chronic administration of PLX5622 in mice and administration of diphtheria toxin to knock-in rats depleted microglia and peripheral tissue macrophages. However, it did not abrogate the inducible expression of proinflammatory cytokines in the brain in response to LPS and even exacerbated it for some of the cytokines. In accordance with these neuroimmune effects, LPS-induced sickness was not abrogated, rather it was exacerbated when measured by running wheel activity in mice. Conclusions: These findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.

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mentioning

confidence: 99%

Microglial ablation in rats disrupts the circadian system

et al. 2020

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Research is increasingly revealing new roles for microglia in the developed brain beyond their well-known function in protecting it from pathogens and injury. 1,2 For example, recent work has demonstrated microglia are likely to be important for memory processing and executive function. [3][4][5][6] Microglial activity directed at pruning of synapses mediates memory degradation in a complement-dependent manner in a contextual fear conditioning task. 3 Likewise, spatial learning is impaired in animals that are unable to reduce their CA1 microglial density during task acquisition 7 and recognition memory is improved when microglia repopulate the brain after depletion. 8 Roles for microglia have also emerged for regulation of feeding and satiety, 9 and in modifying pain responses. 10,11

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Microglial regulation of satiety and cognition

Cited by 22 publications

References 121 publications

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Microglial ablation in rats disrupts the circadian system

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