Astrocyte energy and neurotransmitter metabolism in Alzheimer’s disease: Integration of the glutamate/GABA-glutamine cycle

Progress in Neurobiology, Год журнала: 2022, Номер 217, С. 102331 - 102331

Опубликована: Июль 21, 2022

Язык: Английский

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Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases

CNS Neuroscience & Therapeutics, Год журнала: 2022, Номер 29(1), С. 24 - 36

Опубликована: Окт. 3, 2022

Abstract Astrocytes are the most abundant cells in brain. They have many important functions central nervous system (CNS), including maintenance of glutamate and ion homeostasis, elimination oxidative stress, energy storage glycogen, tissue repair, regulating synaptic activity by releasing neurotransmitters, participating formation. special highly ramified structure. Their branches contact with synapses neurons inwardly, fine structure wrapping synapses; their feet blood vessels brain parenchyma outward, almost whole The adjacent astrocytes rarely overlap communicate each other through gap junction channels. ideal location enables them to sense weak changes surroundings provide structural basis for supply neurons. Neurons closely coupled units metabolism consume a lot ATPs process neurotransmission. metabolic substrates neurons, maintain high neuron, facilitate information transmission This article reviews characteristics glucose metabolism, lipid amino acid astrocytes. interactions between microglia were also detailed discussed. Finally, we classified analyzed role disorder occurrence development neurodegenerative diseases.

Язык: Английский

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Milestone Review: Metabolic dynamics of glutamate and GABA mediated neurotransmission — The essential roles of astrocytes

Journal of Neurochemistry, Год журнала: 2023, Номер 166(2), С. 109 - 137

Опубликована: Март 15, 2023

Abstract Since it was first generally accepted that the two amino acids glutamate and GABA act as principal neurotransmitters, several landmark discoveries relating to this function have been uncovered. Synaptic homeostasis of these transmitters involves cell types working in close collaboration is facilitated by specialized cellular processes. Notably, are extensively recycled between neurons astrocytes a process known glutamate/GABA‐glutamine cycle, which essential maintain synaptic transmission. The cycle intimately coupled energy metabolism relies on metabolic both astrocytes. Importantly, display unique features allowing extensive metabolite release, hereby providing support for neurons. Furthermore, undergo complex adaptations response injury pathology, may greatly affect transmission during disease. In Milestone Review we outline major relation balancing signaling, including uptake, metabolism, recycling. We provide special focus how astrocyte contribute sustain neuronal through transfer. Recent advances reviewed context brain toxicity neurodegeneration. Finally, consider pathological serve potential target intervention. Integrating multitude fine‐tuned processes supporting neurotransmitter recycling, will aid next generation homeostasis. image

Язык: Английский

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Axonal energy metabolism, and the effects in aging and neurodegenerative diseases

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Июль 20, 2023

Abstract Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of (NDAs), such as Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis. Glucose is the major brain fuel glucose hypometabolism has been observed regions vulnerable to NDAs. Many susceptible are topological central hub connectome, linked by densely interconnected long-range axons. Axons, key components have high metabolic needs support neurotransmission other essential activities. Long-range axons particularly injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy often an early sign neurodegeneration. Recent ascribe axonal maintenance failures local dysregulation. With this review, we aim stimulate research exploring metabolically oriented neuroprotection strategies enhance or normalize bioenergetics NDA models. Here start summarizing evidence from human patients animal models reveal correlation between connectomic disintegration aging/NDAs. To encourage mechanistic investigations on how dysregulation occurs during aging/NDAs, first review current literature distinct subdomains: axon initial segments, myelinated arbors harboring pre-synaptic boutons. In each subdomain, focus organization, activity-dependent regulation system, external glial support. Second, mechanisms regulating nicotinamide adenine dinucleotide (NAD + ) homeostasis, molecule for energy metabolism processes, including NAD biosynthetic, recycling, consuming pathways. Third, highlight innate vulnerability connectome discuss its perturbation As deficits developing into NDAs, especially asymptomatic phase, they likely exaggerated further impaired energetic cost neural network hyperactivity, pathology. Future interrogating causal relationship vulnerability, axonopathy, amyloid/tau pathology, cognitive decline will provide fundamental knowledge therapeutic interventions.

Язык: Английский

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Inflammatory aspects of Alzheimer’s disease

Acta Neuropathologica, Год журнала: 2024, Номер 148(1)

Опубликована: Авг. 28, 2024

Язык: Английский

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Glucose Metabolism, Neural Cell Senescence and Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(8), С. 4351 - 4351

Опубликована: Апрель 14, 2022

Alzheimer’s disease (AD), an elderly neurodegenerative disorder with a high incidence and progressive memory decline, is one of the most expensive, lethal, burdening diseases. To date, pathogenesis AD has not been fully illustrated. Emerging studies have revealed that cellular senescence abnormal glucose metabolism in brain are early hallmarks AD. Moreover, disturbance patients may precede amyloid-β deposition or Tau protein phosphorylation. Thus, metabolic reprogramming targeting senescent microglia astrocytes be novel strategy for intervention treatment. Here, we recapitulate relationships between neural cell (e.g., insulin signaling, lactate metabolism) We then discuss potential perspective towards intervention, providing theoretical basis further exploration therapeutic approach toward

Язык: Английский

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Glial Glutamine Homeostasis in Health and Disease

Neurochemical Research, Год журнала: 2022, Номер 48(4), С. 1100 - 1128

Опубликована: Ноя. 2, 2022

Язык: Английский

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Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models

Molecular Psychiatry, Год журнала: 2023, Номер 28(9), С. 3966 - 3981

Опубликована: Сен. 1, 2023

Accumulation of amyloid β-peptide (Aβ) is a driver Alzheimer's disease (AD). Amyloid precursor protein (App) knock-in mouse models recapitulate AD-associated Aβ pathology, allowing elucidation downstream effects accumulation and their temporal appearance upon progression. Here we have investigated the sequential onset AD-like pathologies in AppNL-F AppNL-G-F mice by time-course transcriptome analysis hippocampus, region severely affected AD. Strikingly, energy metabolism emerged as one most significantly altered pathways already at an early stage pathology. Functional experiments isolated mitochondria from hippocampus both confirmed upregulation oxidative phosphorylation driven activity mitochondrial complexes I, IV V, associated with higher susceptibility to damage Ca2+-overload. Upon increasing pathologies, brain shifts state hypometabolism reduced abundancy presynaptic terminals. These late-stage also displayed enlarged areas abnormal synaptic vesicles autophagosomes, latter ultimately leading local autophagy impairment synapses. In summary, report that Aβ-induced App key observed AD brain, our data herein adds comprehensive understanding including dysregulated synapses timewise find new therapeutic approaches for

Язык: Английский

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Astrocytes regulate inhibitory neurotransmission through GABA uptake, metabolism, and recycling

Essays in Biochemistry, Год журнала: 2023, Номер 67(1), С. 77 - 91

Опубликована: Фев. 21, 2023

Abstract Synaptic regulation of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) is essential for brain function. Cerebral GABA homeostasis tightly regulated through multiple mechanisms and directly coupled to metabolic collaboration between neurons astrocytes. In this essay, we outline discuss fundamental roles astrocytes in regulating synaptic signaling. A major fraction removed from synapse by astrocytic uptake. Astrocytes utilize as a substrate support glutamine synthesis. The astrocyte-derived subsequently transferred where it serves precursor neuronal flow collectively termed GABA-glutamine cycle sustain synthesis certain areas, are even capable synthesizing releasing modulate transmission. majority oxidative metabolism takes place astrocytes, which also leads GABA-related metabolite γ-hydroxybutyric (GHB). physiological endogenous GHB remain unclear, but may be related tonic inhibition plasticity. Disrupted signaling dysfunctional astrocyte handling implicated several diseases including epilepsy Alzheimer’s disease. under control uptake, metabolism, recycling therefore serve relevant targets ameliorate pathological

Язык: Английский

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Astrocytic modulation of neuronal signalling

Frontiers in Network Physiology, Год журнала: 2023, Номер 3

Опубликована: Июнь 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Язык: Английский

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