Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases

Bickford, Paula C.; Flowers, Antwoine; Grimmig, Bethany

doi:10.1016/j.exger.2017.01.027

Cited by 33 publications

(23 citation statements)

References 41 publications

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“…Activated microglia driving chronic neuroinflammation have also been shown to substantially contribute to aging of the CNS [ 259 , 260 ], epilepsy [ 261 ], chronic neuropathic pain [ 262 ], mental diseases [ 35 , 263 , 264 ] and neurodegenerative diseases, including Alzheimer’s disease [ 222 ], Parkinson’s disease [ 265 ], amyotrophic lateral sclerosis (ALS) [ 34 ] and multiple sclerosis [ 33 ]. Aging goes in parallel with systemic chronic activation of the immune system and polarization towards a low-level inflammatory status [ 266 , 267 ].…”

Section: Introductionmentioning

confidence: 99%

“…Aging goes in parallel with systemic chronic activation of the immune system and polarization towards a low-level inflammatory status [ 266 , 267 ]. This process also affects the CNS and thus microglia [ 259 , 268 ], which interferes with CNS homeostasis, especially adult neurogenesis [ 269 ], the function and structure of myelination [ 270 ] and synapses, as well as the BBB. Mental and neurodegenerative diseases have then probably to be seen as focal processes of age-related activated and dysfunctional microglia [ 45 , 271 – 274 ]).…”

Section: Introductionmentioning

confidence: 99%

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Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

et al. 2017

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Microglia cells are the unique residential macrophages of the central nervous system (CNS). They have a special origin, as they derive from the embryonic yolk sac and enter the developing CNS at a very early stage. They play an important role during CNS development and adult homeostasis. They have a major contribution to adult neurogenesis and neuroinflammation. Thus, they participate in the pathogenesis of neurodegenerative diseases and contribute to aging. They play an important role in sustaining and breaking the blood-brain barrier. As innate immune cells, they contribute substantially to the immune response against infectious agents affecting the CNS. They play also a major role in the growth of tumours of the CNS. Microglia are consequently the key cell population linking the nervous and the immune system. This review covers all different aspects of microglia biology and pathology in a comprehensive way.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

et al. 2017

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“…The capacity for microglia to stay regulated can be conceptualized as a key component to the brain's resilience against future neurological disease 169,170 . When microglia become primed, as they do following TBI, the immune system of the CNS becomes less resilient to future internal or external stressors.…”

Section: Potential Clinical Implicationsmentioning

confidence: 99%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

150

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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“…This process is altered in aged microglia (Hayashi et al, 2006 ). Furthermore, aging leads to impaired microglial function, which results in reduced brain resiliency, thereby increasing susceptibility to neurodegenerative diseases (Bickford et al, 2017 ).…”

Section: Nmda Receptor Microglia Dendritic Spines and Agingmentioning

confidence: 99%

Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

et al. 2017

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Molecular changes associated with neuronal aging lead to a decrease in cognitive capacity. Here we discuss these alterations at the level of brain regions, brain cells, and brain membrane and cytoskeletal proteins with an special focus in NMDA molecular changes through aging and its effect in cognitive decline and Alzheimer disease. Here, we propose that some neurodegenerative disorders, like Alzheimer's disease (AD), are characterized by an increase and acceleration of some of these changes.

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Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases

Cited by 33 publications

References 41 publications

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

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