Lipid Metabolism Crosstalk in the Brain: Glia and Neurons

Barber, Casey N.; Raben, Daniel M.

doi:10.3389/fncel.2019.00212

Cited by 127 publications

(113 citation statements)

References 45 publications

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“…Fatty acids and KBs form the second metabolic compartment between neurons and astroglia (Fig. ) . KBs, consisting of acetoacetate (AA), acetone, and β‐hydroxybutyrate (BHB), are alternative substrates for glucose.…”

Section: Fatty Acid and Kbmentioning

confidence: 99%

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Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and microvasculature in the brain gray matter. They play a pivotal role in brain metabolism as well as in the regulation of cerebral blood flow, taking advantage of their unique anatomical location. In particular, the astroglial cellular metabolic compartment exerts supportive roles in dedicating neurons to the generation of action potentials and protects them against oxidative stress associated with their high energy consumption. An impairment of normal astroglial function, therefore, can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuroimmunological diseases, in which metabolic derangements accelerate neuronal damage. The neurovascular unit (NVU), the major components of which include neurons, microvessels, and astroglia, is a conceptual framework that was originally used to better understand the pathophysiology of cerebral ischemia. At present, the NVU is a tool for understanding normal brain physiology as well as the pathophysiology of numerous neurological disorders. The metabolic responses of astroglia in the NVU can be either protective or deleterious. This review focuses on three major metabolic compartments: (i) glucose and lactate; (ii) fatty acid and ketone bodies; and (iii) D‐ and L‐serine. Both the beneficial and the detrimental roles of compartmentalization between neurons and astroglia will be discussed. A better understanding of the astroglial metabolic response in the NVU is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.

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Section: Fatty Acid and Kbmentioning

confidence: 99%

“…4). [126][127][128][129][130][131] KBs, consisting of acetoacetate (AA), acetone, and β-hydroxybutyrate (BHB), are alternative substrates for glucose. KBs, rather than glucose, are the main energy substrates in the brains of infants.…”

Section: Kbs Produced From Fatty Acids Serve As Energy Substrates Formentioning

confidence: 99%

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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“…Neuron-glial cell communication in lipid metabolism is necessary to regulate the neuronal functions such as neurotransmission and neural development [15]. It is well-known that astrocytes provide lactate and ketone bodies to neurons through the catabolism of MCFAs [4].…”

Section: Discussionmentioning

confidence: 99%

“…They contribute to the maintenance of neuro-immune interactions [13,14]. Celluler communication between neurons and astrocytes is important for neuronal functions such as neurotransmitter release, protection of activity-induced lipotoxicity, and the maintenance of neuronal environment [15,16]. Astrocytes produce growth factors and cytokines in response to extracellular stimuli [17,18].…”

Section: Introductionmentioning

confidence: 99%

Lauric acid promotes neuronal maturation mediated by astrocytes in primary cortical cultures

Nakajima

2020

Heliyon

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Previous studies have suggested the potential efficacy of middle chain fatty acids (MCFAs) in the treatment of mood disorders and cognitive dysfunction. MCFAs are metabolized to ketone bodies in astrocytes; however, their effects on neuronal development including neurotrophic factor level are not well-understood. In the present study, we examined the effect of MCFAs on the mRNA expression of growth factors and cytokines in primary cultures of cortical astrocytes. The effect of MCFAs on neuron-astrocyte interaction in neuronal maturation was also determined using co-culture and astrocyte-conditioned medium. Lauric acid (LA) typically increased the mRNA expression of glial-derived neurotrophic factor (Gdnf), interleukin-6 (Il6), and CC motif chemokine 2 (Ccl2) in astrocytes. LA-induced phosphorylation of extracellular signalregulated kinase contributed to these changes. In primary cultures of cortical neurons containing astrocytes, LA enhanced the presynaptic protein levels. Astrocyte-conditioned medium after LA treatment also enhanced the presynaptic protein levels in the cortical neuron cultures. These results suggest that LA increase the mRNA expression of GDNF and cytokines in astrocytes, and thereby, enhances the presynaptic maturation.

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“…Many of the >60 LSDs display neuropathological phenotypes, highlighting the essential role of the endolysosomal system in brain cells. Endolysosomes are critical to the processing of metabolites in astrocytes, ensuring that reactive metabolites are sequestered from the neuron and converted into storage or energy precursors for neuronal use [ 7 , 16 , 17 ]. Endolysosomal dysfunction in LSDs thus impacts on the neuro-supportive role of astrocytes and exacerbates neurologic deficits.…”

Section: Astrocytes In Lysosomal Storage Diseasesmentioning

confidence: 99%

Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes

Wong

2020

IJMS

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Most common neurodegenerative diseases (NDs) are characterized by deposition of protein aggregates that are resulted from misfolding, dysregulated trafficking, and compromised proteolytic degradation. These proteins exert cellular toxicity to a broad range of brain cells and are found in both neurons and glia. Extracellular monomeric and oligomeric ND-associated proteins are taken up by astrocytes, the most abundant glial cell in the brain. Internalization, intracellular trafficking, processing, and disposal of these proteins are executed by the endosomal-lysosomal system of astrocytes. Endosomal-lysosomal organelles thus mediate the cellular impact and metabolic fate of these toxic protein species. Given the indispensable role of astrocytes in brain metabolic homeostasis, the endosomal-lysosomal processing of these proteins plays a fundamental role in altering the trajectory of neurodegeneration. This review aims at summarizing the mounting evidence that has established the essential role of astrocytic endosomal-lysosomal organelles in the processing of amyloid precursor proteins, Apolipoprotein E (ApoE), tau, alpha synuclein, and huntingtin, which are associated with NDs such as Alzheimer’s, Parkinson’s, and Huntington diseases.

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Lipid Metabolism Crosstalk in the Brain: Glia and Neurons

Cited by 127 publications

References 45 publications

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Lauric acid promotes neuronal maturation mediated by astrocytes in primary cortical cultures

Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes

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