Inflammatory Milieu Induces Mitochondrial Alterations and Neuronal Activations in Hypothalamic POMC Neurons in a Time-Dependent Manner

Liao, Yi-Chun; Lim, Yeou San; Chu, Pei-Wen; Chen, Shau-Kwaun

doi:10.1007/s12035-022-03128-3

Cited by 4 publications

(4 citation statements)

References 54 publications

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“…Mitochondrial dysfunction is key for neurodegenerative diseases [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ]. Mitochondria are at the core of cellular energy production and interruption of the crosstalk between cell signaling and mitochondrial functions and biogenesis, and result in mitochondrial dysfunction, proteotoxic stress, accumulation of defective mitochondria, and the production of reactive oxygen species due to defective mitophagy and major alterations in the ubiquitin–proteasome system [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ,…”

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

“…Since myelination is an energy-consuming event, as described by Gil et al [ 108 ], oligodendrocyte development and mitochondrial-mediated mechanisms to oligodendrocyte bioenergetics and development, as well as mitochondrial development in utero are also relevant to neurodegeneration [ 109 , 110 , 111 , 112 ]. Inflammatory environments negatively impact mitochondria, as shown by Liao et al [ 113 ], using conditioned medium from LPS-activated macrophages in mice hypothalamic neurons resulting in elevated intracellular ROS/RNS levels and reduced antioxidant enzymes. Interestingly, LPS exposures not only affected mitochondrial respiration and functions, but also resulted in the elongation of mitochondria after a 24 h treatment.…”

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

“…Interestingly, LPS exposures not only affected mitochondrial respiration and functions, but also resulted in the elongation of mitochondria after a 24 h treatment. The authors concluded that LPS chronic exposure significantly increased oxidative stress, decreased mitochondrial respiration, and altered mitochondrial dynamics [ 113 ]—the issue is of utmost importance in urbanites exposed to LPS-associated fine particulate matter [ 123 ].…”

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

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APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

Calderón‐Garcidueñas

Hernández-Luna²,

Aiello-Mora

et al. 2023

Biomolecules

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This Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM2.5), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden—as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs—in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aβ42)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer’s Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aβ42 abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM2.5, UFP, and NP emissions from all sources are urgently needed. Alzheimer’s Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported.

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Section: Apoe4 Brain Effectsmentioning

confidence: 99%

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

See 1 more Smart Citation

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

Calderón‐Garcidueñas

Hernández-Luna²,

Aiello-Mora

et al. 2023

Biomolecules

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“…Both MIGF2 secretome or rIGF2 reduced mitochondrial dysfunction, trigger by α-syn oligomers. The mitochondrial oxygen consumption by neurons is very variable, ranging from approximately 6 to 7% in resting situation to up to 80% in firing neurons; thus, deterioration in mitochondrial respiration capacity is crucial to neuronal viability (88,89). rIGF2 or MIGF2 secretome probably prevents the neuronal death by restore of mitochondrial activity in PD cellular model.…”

mentioning

confidence: 99%

IGF2-reprogrammed macrophages ameliorate the inflammatory response and protects against the neurodegenerative and neuroinflammatory process in Parkinson`s disease models.

Grunenwald,

Huerta,

Sepulveda

et al. 2024

Preprint

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Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra, which causes motor deficits. The most common histopathological feature of PD is the presence of α-synuclein (α-syn) misfolding protein and neurotoxic accumulations which leads to neuronal loss. Additionally, the inflammatory response arises as a relevant factor engage in modulate the neurodegeneration process in PD. An increase of proinflammatory cytokines in the blood and brain samples has been reported in PD patients. Also, peripheral blood T cells recognized α-syn, triggering a chronic inflammation in the blood and brain tissue in PD. IGF2 signaling has been involved on cellular reprogramming of macrophages to anti-inflammatory phenotype by epigenetic changes. Moreover, recently a decrease of IGF2 levels was reported in blood samples from PD patients. Methods: The inflammatory response was analyzed by flow cytometry, and qPCR in PBMCs from Chilean PD patients and macrophages isolated from α-syn overexpression transgenic mouse (ASO). We evaluated the motor impairment, systemic inflammation, neurodegeneration, α-syn accumulation and microglial activation in ASO mice treated via intravenous with IGF2-reprogrammed macrophages (MIGF2). Results: We showed a significant increase of proinflammatory markers in PBMCs from PD patients. Also, IGF2 prevented the proinflammatory phenotype triggered by exposure to α-syn PFF in murine primary macrophages. Furthermore, MIGF2 treatment significant decrease the motor impairment, systemic inflammation, and reduce neurodegeneration, α-syn accumulation and microglial activation levels in Substancia Nigra brain region during disease progression in ASO mice. Conclusions: PBMCs from Chilean PD patients showed an increase in proinflammatory profile. Additionally, MIGF2 has a neuroprotective effect in-vitro and in-vivo PD model. MIGF2 prevents motor impairment, neurodegeneration, and inflammation in the brain tissue of ASO mice in different stages of disease progression, suggesting its further application as a possible treatment for PD patients.

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Mitochondrial influences on smooth muscle phenotype

Pearce

2024

American Journal of Physiology-Cell Physiology

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Smooth muscle cells transition reversibly between contractile and non-contractile phenotypes in response to diverse influences, including many from mitochondria. Numerous molecules including myocardin, pro-contractile miRNAs, and the mitochondrial protein Prohibitin-2 promote contractile differentiation; this is opposed by mitochondrial reactive oxygen species (mtROS), high lactate concentrations, and metabolic reprogramming induced by mitophagy and/or mitochondrial fission. A major pathway through which vascular pathologies such as oncogenic transformation, pulmonary hypertension, and atherosclerosis cause loss of vascular contractility is by enhancing mitophagy and mitochondrial fission with secondary effects on smooth muscle phenotype. Pro-proliferative miRNAs and the mitochondrial translocase TOMM40 also attenuate contractile differentiation. Hypoxia can initiate loss of contractility by enhancing mtROS and lactate production while simultaneously depressing mitochondrial respiration. Mitochondria can reduce cytosolic calcium by moving it across the inner mitochondrial membrane via the Mitochondrial Calcium Uniporter, and then through Mitochondria Associated Membranes to and from calcium stores in the sarcoplasmic/endoplasmic reticulum. Through these effects on calcium, mitochondria can influence multiple calcium-sensitive nuclear transcription factors and genes, some of which govern smooth muscle phenotype, and possibly also the production of genomically encoded mitochondrial proteins and miRNAs (mitoMirs) that target the mitochondria. In turn, mitochondria also can influence nuclear transcription and mRNA processing through Mitochondrial Retrograde Signaling, which is currently a topic of intensive investigation. Mitochondria also can signal to adjacent cells by contribution to the content of exosomes. Considering these and other mechanisms, it is becoming increasingly clear that mitochondria contribute significantly to regulation of smooth muscle phenotype and differentiation.

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Inflammatory Milieu Induces Mitochondrial Alterations and Neuronal Activations in Hypothalamic POMC Neurons in a Time-Dependent Manner

Cited by 4 publications

References 54 publications

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

IGF2-reprogrammed macrophages ameliorate the inflammatory response and protects against the neurodegenerative and neuroinflammatory process in Parkinson`s disease models.

Mitochondrial influences on smooth muscle phenotype

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