Advances in neurobiology, Journal Year: 2023, Volume and Issue: unknown, P. 255 - 310
Published: Jan. 1, 2023
Language: Английский
Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 18(11), P. 2327 - 2340
Published: March 2, 2022
Abstract Objective Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test hypothesis that neuroinflammation is directly involved development synaptic/neuronal loss and cognitive decline. Background Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful mitigating AD‐associated impairment. Identification new drug targets needed. Neuroinflammation a therapeutic target neurodegenerative disorders, TNF‐α pivotal neuroinflammatory driver. New chronic drives progressive Pharmacologically microglial/astrocyte activation without altering Aβ generation will define role AD progression. Major challenges Difficulty TNF‐α‐lowering compounds reaching brain, identification therapeutic‐time window preserve beneficial processes. Linkage other major theories Microglia/astroglia are heavily implicated maintenance synaptic plasticity/function healthy brain disrupted by Aβ. Mitigation gliosis can restore homeostasis/cognitive function.
Language: Английский
Citations
125
Developmental Neurobiology, Journal Year: 2021, Volume and Issue: 81(5), P. 568 - 590
Published: Feb. 14, 2021
Synapses are fundamental structures of neural circuits that transmit information between neurons. Thus, the process circuit formation via proper synaptic connections shapes basis brain functions and animal behavior. continuously undergo repeated elimination throughout lifetime an organism, reflecting dynamics function. The structural transformation synapses has been described mainly in relation to activity-dependent strengthening weakening functions, is, functional plasticity synapses. An increasing number studies have unveiled roles microglia, brain-resident immune cells survey parenchyma with highly motile processes, synapse as well regulating Over past 15 years, molecular mechanisms underlying microglia-dependent regulation thoroughly studied, researchers reported disruption causes dysfunction leads diseases. In this review, we will broadly introduce report microglia possible mechanisms.
Language: Английский
Citations
124
Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 96 - 107
Published: Dec. 6, 2022
Microglia are resident immune cells in the central nervous system, playing critical roles brain development and homeostasis. Increasing evidence has implicated microglia dysfunction pathogenesis of various disorders ranging from psychiatric to neurodegenerative diseases. Using a human cell-based model illuminate functional mechanisms will promote pathological studies drug development. The recently developed microglia-containing organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features brain, have provided new avenue pathology. However, MC-HBOs generated different methods differ origin, proportion, fidelity within organoids, may produced inconsistent results. To help researchers develop robust reproducible recapitulates in-vivo signatures study pathology, this review summarized current used generate opinions on use for disease modeling studies.
Language: Английский
Citations
82
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13
Published: Feb. 2, 2023
Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.
Language: Английский
Citations
75
Inflammation Research, Journal Year: 2023, Volume and Issue: 72(3), P. 443 - 462
Published: Jan. 4, 2023
Language: Английский
Citations
51
Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(8), P. 2424 - 2437
Published: March 18, 2024
Language: Английский
Citations
18
Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 80 - 99
Published: Jan. 6, 2024
Language: Английский
Citations
17
Clinical Interventions in Aging, Journal Year: 2022, Volume and Issue: Volume 17, P. 665 - 674
Published: April 1, 2022
Abstract: Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), precise pathophysiology this deadly illness remains unclear and no effective remedies capable inhibiting progression have been discovered. In addition to deposition extracellular Aβ plaques intracellular neurofibrillary tangles, neuroinflammation has identified third core characteristic crucial AD. More more evidence from laboratory clinical studies suggested that anti-inflammatory treatments could defer or prevent occurrence review, we will discuss multifaceted presented AD newly emerged targets both pre-clinical Keywords: disease, neuroinflammation, disease‐modifying therapy, treatment
Language: Английский
Citations
54
Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)
Published: Sept. 6, 2023
The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces decline accompanied by alterations the gut microbiota. However, of microbiota SD-induced dysfunction and underlying mechanisms remain unclear. Here, we found that dysbiosis following pretreatment with broad-spectrum antibiotics worsens impairment mice. Fecal transplantation from SD mice to healthy induced Additionally, abundance Akkermansia muciniphila (A. muciniphila) mouse was significantly reduced after 7 days SD. A. alleviated prevented synaptic reduction hippocampus inhibited extensive microglial activation engulfment Metabolomics analysis revealed increased serum acetate butanoic acid levels Finally, short-chain fatty acids (SCFAs) neuronal loss primary microglia-neuron co-culture LPS stimulation. Together, our findings illustrate an essential activating at synapses. supplementation may be novel preventative strategy for dysfunction, increasing SCFAs production maintaining homeostasis.
Language: Английский
Citations
39
Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(30)
Published: July 11, 2023
Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo -inositol as a component that promotes development. We determined it is most abundant in during early lactation when neuronal connections rapidly form infant brain. Myo promoted synapse abundance excitatory neurons well cultured rat and acted dose-dependent manner. Mechanistically, enhanced ability to respond transsynaptic interactions induce synapses. developing were tested mice, its dietary supplementation enlarged postsynaptic sites maturing cortex. Utilizing an organotypic slice culture system, additionally bioactive mature tissue, treatment slices with this increased number size specializations density. This study advances our understanding impact identifies breast formation connections.
Language: Английский
Citations
29