Lifestyle-dependent microglial plasticity: training the brain guardians

Augusto-Oliveira, Marcus; Verkhratsky, Alexei

doi:10.1186/s13062-021-00297-4

Cited by 20 publications

(15 citation statements)

References 150 publications

(152 reference statements)

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“…Using double labeling of Iba-+ and CD68+ [ 63 ], we have previously shown the increased presence of phagocytic microglia cells in the DG of HAB [ 31 ]. Therefore, besides investigating Iba-1 as a marker for microglia [ 64 ], we next aimed to determine the expression levels of the phagocytosis/antigen-presentation marker CD68 within Iba-1+ cells in the DG. We now demonstrate that the EE reduces CD68 expression in microglia in the DG of HAB in association with successful anxiolysis.…”

Section: Discussionmentioning

confidence: 99%

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events

Sah

Rooney

Kharitonova

et al. 2022

IJMS

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Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, “positive environmental stimuli”, which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety.

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Section: Discussionmentioning

confidence: 99%

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events

Sah

Rooney

Kharitonova

et al. 2022

IJMS

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“…The western diet is known to shift immune cell balance, promote cancer progression, and be at the roots of multiple problems in human health during aging, from metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration [4][5][6][7]. The western diet is rich in triglycerides which, once ingested, are processed by gastrointestinal lipases to be assimilated as fatty acids (FA).…”

Section: Introductionmentioning

confidence: 99%

Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis

et al. 2022

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Background In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142–143, 2021; Ilacqua et al. in J Cell Sci 135:1–11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown. Methods We evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers. Results The expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration. Conclusion Synj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux.

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“…Adult hippocampal neurogenesis is a striking form of neural plasticity that occurs in the brains of numerous mammalian species. It is regulated by several lifestyle factors, including exercise, diet, and social interactions ( Valero et al, 2016 ; Augusto-Oliveira and Verkhratsky, 2021 ). Augusto-Oliveira and Verkhratsky (2021) reviewed how the adoption of a healthy lifestyle, including regular exercise, intellectual engagement, and friendly diet, impacts brain physiology from a molecular biological perspective.…”

Section: Brain Reservementioning

confidence: 99%

“…It is regulated by several lifestyle factors, including exercise, diet, and social interactions ( Valero et al, 2016 ; Augusto-Oliveira and Verkhratsky, 2021 ). Augusto-Oliveira and Verkhratsky (2021) reviewed how the adoption of a healthy lifestyle, including regular exercise, intellectual engagement, and friendly diet, impacts brain physiology from a molecular biological perspective. Lifestyle factors are associated with arresting or retarding neurodegenerative alterations, for example, exposure to an enriched environment results in well-characterized beneficial effects on the central nervous system, including boosting adult neurogenesis, synaptic plasticity, cellular physiology, and remodeling of the neuroglia.…”

Section: Brain Reservementioning

confidence: 99%

Aging Brain and Hearing: A Mini-Review

Uchida

Nishita

Otsuka

et al. 2022

Front. Aging Neurosci.

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Brain reserve is a topic of great interest to researchers in aging medicine field. Some individuals retain well-preserved cognitive function until they fulfill their lives despite significant brain pathology. One concept that explains this paradox is the reserve hypothesis, including brain reserve that assumes a virtual ability to mitigate the effects of neuropathological changes and reduce the effects on clinical symptoms flexibly and efficiently by making complete use of the cognitive and compensatory processes. One of the surrogate measures of reserve capacity is brain volume. Evidence that dementia and hearing loss are interrelated has been steadily accumulating, and age-related hearing loss is one of the most promising modifiable risk factors of dementia. Research focused on the imaging analysis of the aged brain relative to auditory function has been gradually increasing. Several morphological studies have been conducted to understand the relationship between hearing loss and brain volume. In this mini review, we provide a brief overview of the concept of brain reserve, followed by a small review of studies addressing brain morphology and hearing loss/hearing compensation, including the findings obtained from our previous study that hearing loss after middle age could affect hippocampal and primary auditory cortex atrophy.

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Lifestyle-dependent microglial plasticity: training the brain guardians

Cited by 20 publications

References 150 publications

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events

Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis

Aging Brain and Hearing: A Mini-Review

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