Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Язык: Английский

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The link between neuroinflammation and the neurovascular unit in synucleinopathies

Science Advances, Год журнала: 2023, Номер 9(7)

Опубликована: Фев. 15, 2023

The neurovascular unit (NVU) is composed of vascular cells, glial and neurons. As a fundamental functional module in the central nervous system, NVU maintains homeostasis microenvironment integrity blood-brain barrier. Disruption interactions among its components are involved pathophysiology synucleinopathies, which characterized by pathological accumulation α-synuclein. Neuroinflammation contributes to including Parkinson's disease, multiple system atrophy, dementia with Lewy bodies. This review aims summarize neuroinflammatory response cells NVU. We also neuroinflammation context cross-talk between pericytes, microglia astroglia. Last, we discuss how α-synuclein affects influences aggregation spread analyze different properties synucleinopathies.

Язык: Английский

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Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6521 - 6521

Опубликована: Июнь 13, 2024

Glutamate is the main excitatory neurotransmitter in brain wherein it controls cognitive functional domains and mood. Indeed, areas involved memory formation consolidation as well fear emotional processing, such hippocampus, prefrontal cortex, amygdala, are predominantly glutamatergic. To ensure physiological activity of brain, glutamatergic transmission finely tuned at synaptic sites. Disruption mechanisms responsible for glutamate homeostasis may result accumulation excessive levels, which turn leads to increased calcium mitochondrial abnormalities, oxidative stress, eventually cell atrophy death. This condition known glutamate-induced excitotoxicity considered a pathogenic mechanism several diseases central nervous system, including neurodevelopmental, substance abuse, psychiatric disorders. On other hand, these disorders share neuroplasticity impairments areas, accompanied by structural remodeling neurons. In current narrative review, we will summarize role both pathophysiology therapeutic interventions neurodevelopmental adult mental with focus on autism spectrum disorders, drugs under preclinical clinical development treatment different that dysfunctions. Although evidence still limited more studies required, regulation attracting attention potential crucial target control diseases.

Язык: Английский

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Astrocyte regulation of synaptic signaling in psychiatric disorders

Neuropsychopharmacology, Год журнала: 2022, Номер 48(1), С. 21 - 36

Опубликована: Май 16, 2022

Язык: Английский

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The Crosstalk Between Neurons and Glia in Methamphetamine-Induced Neuroinflammation

Neurochemical Research, Год журнала: 2022, Номер 47(4), С. 872 - 884

Опубликована: Янв. 4, 2022

Язык: Английский

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Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

PLoS Biology, Год журнала: 2024, Номер 22(7), С. e3002687 - e3002687

Опубликована: Июль 11, 2024

Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms unclear. We used optogenetic chemogenetic tools to identify crucial roles of hippocampal CA1 decline. Our results showed that repeated stimulation induced impairment mice decreased synaptic long-term potentiation (LTP), which was accompanied by appearance inflammatory astrocytes. Mechanistic studies conducted using knockout animal models neuronal cultures lipocalin-2 (LCN2), derived from reactive astrocytes, mediated decreasing LTP through reduction NMDA receptors. Sustained provided similar results. Conversely, these phenomena were attenuated a metabolic inhibitor Fiber photometry GCaMP revealed high level astrocyte activation model. findings suggest hippocampus sufficient required induce LCN2 release modulation. This abnormal glial–neuron interaction may contribute pathogenesis disturbances neuroinflammation-associated brain conditions.

Язык: Английский

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Inflammaging and Brain Aging

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10535 - 10535

Опубликована: Сен. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Язык: Английский

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The interaction between central and peripheral immune systems in methamphetamine use disorder: current status and future directions

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 15, 2025

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive drug-seeking behavior and substantial neurotoxicity, posing a considerable burden on individuals society. Traditionally perceived as localized central nervous system disorder, recent preclinical clinical studies have elucidated that MUD multifaceted influenced various biological systems, particularly the immune system. Emerging evidence suggests both peripheral responses play crucial role in initiation persistence of MUD. Conceptualizing it systemic process prompts significant inquiries regarding mechanisms communication between compartments. Also, whether this intercommunication could serve diagnostic biomarkers or therapeutic targets. This review begins offering an overview mechanistic pertaining to neuroimmune systems. Finally, future directions are suggested through integration innovative technologies multidimensional data promote translation basic research into interventions.

Язык: Английский

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Bidirectional Communication Between Microglia and Astrocytes in Neuroinflammation

Current Neuropharmacology, Год журнала: 2022, Номер 21(10), С. 2020 - 2029

Опубликована: Дек. 2, 2022

Abstract: Neuroinflammation is a common feature of diverse nervous system pathologies. In many instances, it begins at an early stage the disease, paving way for further exacerbations. The main drivers neuroinflammation are brain-resident glial cells, such as microglia and astrocytes. Microglia primary responders to any insult brain parenchyma, translating signals into molecules. These molecules derived from can regulate stimuli-dependent reactivity Once activated, astrocytes in turn, control phenotypes. Recent evidence indicates that crosstalk between these cells plays important role delaying or accelerating overall disease progression. To date, various have been recognized key mediators bidirectional communication current review aims discuss novel identified recently, which play critical interglial crosstalk, highlighting their therapeutic potential.

Язык: Английский

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Gut-derived bacterial LPS attenuates incubation of methamphetamine craving via modulating microglia

Brain Behavior and Immunity, Год журнала: 2023, Номер 111, С. 101 - 115

Опубликована: Апрель 1, 2023

Язык: Английский

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