Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function

Sun, Jian; Zhu, Kun; Wang, Yumeng; Wang, Dan-jie; Zhang, Mi-zhen; Sarlus, Heela; Benito-Cuesta, Irene; Zhao, Xiaoqiang; Zou, Zaofeng; Zhong, Qing-yang; Yue, Feng; Wu, Shuai; Wang, Yan-Qing; Harris, R. Adron; Wang, Jun

doi:10.1038/s41401-022-01000-7

Cited by 10 publications

(8 citation statements)

References 62 publications

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“…Whether the effects of LIPUS could be beneficial or detrimental to resolution of neuroinflammation largely depends on the underlying mechanisms and pathways it engages. For example, the activation of TRPA1 receptors may exacerbate myelin damage and reduce cognitive outcomes 112 , while activating TRPV1 receptor facilitates myelin repair which are important mechanisms for functional recovery 113 . Several channels and receptors can modulate microglial activity including microglial migration, ramification, and surveillance 85,[113][114][115] .…”

Section: Discussionmentioning

confidence: 99%

“…For example, the activation of TRPA1 receptors may exacerbate myelin damage and reduce cognitive outcomes 112 , while activating TRPV1 receptor facilitates myelin repair which are important mechanisms for functional recovery 113 . Several channels and receptors can modulate microglial activity including microglial migration, ramification, and surveillance 85,[113][114][115] . Notably, the activation of TRPV1 receptors boosts the microglia migration 113 , potentially contributing to the observed increase in microglial migration on day 1 and day 3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Several channels and receptors can modulate microglial activity including microglial migration, ramification, and surveillance 85,[113][114][115] . Notably, the activation of TRPV1 receptors boosts the microglia migration 113 , potentially contributing to the observed increase in microglial migration on day 1 and day 3 (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

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Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

Li,

Gallego,

Tirko

et al. 2023

Preprint

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Microglia are important players in surveillance and repair of the brain. Their activation mediates neuroinflammation caused by intracortical microelectrode implantation, which impedes the application of intracortical brain-computer interfaces (BCIs). While low-intensity pulsed ultrasound stimulation (LIPUS) can attenuate microglial activation, its potential to modulate the microglia-mediated neuroinflammation and enhance the bio-integration of microelectrodes remains insufficiently explored. We found that LIPUS increased microglia migration speed from 0.59±0.04 to 1.35±0.07 µm/hr on day 1 and enhanced microglia expansion area from 44.50±6.86 to 93.15±8.77 µm2/min on day 7, indicating improved tissue healing and surveillance. Furthermore, LIPUS reduced microglial activation by 17% on day 6, vessel-associated microglia ratio from 70.67±6.15 to 40.43±3.87% on day 7, and vessel diameter by 20% on day 28. Additionally, microglial coverage of the microelectrode was reduced by 50% in week 1, indicating better tissue-microelectrode integration. These data reveal that LIPUS helps resolve neuroinflammation around chronic intracortical microelectrodes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

Li,

Gallego,

Tirko

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, TRPV2 mediates PDK1/Akt-dependent phagocytosis and increased mRNA expression of phagocytosis related receptors, crucial for autophagy [87]. Moreover, CBD effectively reduces neuroinflammation by improving mitochondrial function and ATP production via TRPV2 activation [88]. Therefore, TRPV2 and other TRP channels/receptors, along with TREM2 and TREM1, could also be potential therapeutic targets in AD.…”

Section: Pharmacological Interventions For Ecs In Alzheimer's Diseasementioning

confidence: 99%

Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer’s Disease

Kanwal,

Sangineto,

Ciarnelli

et al. 2024

IJMS

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Alzheimer’s disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.

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“…This protective mechanism may entail capsaicin's pharmacological stimulation of TRPV1, which targets the mTOR-HIF-1α pathway. Capsaicin restores microglial energy metabolism, improves phagocytosis, and facilitates the degenerative processes identified in AD and PD disease models [ 44 , 142 , 146 , 147 ].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

Huang,

Wang,

Chen

et al. 2023

Aging and disease

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Neurodegenerative diseases (ND) are conditions defined by progressive deterioration of the structure and function of the nervous system. Some major examples include Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). These diseases lead to various dysfunctions, like impaired cognition, memory, and movement. Chronic neuroinflammation may underlie numerous neurodegenerative disorders. Microglia, an important immunocell in the brain, plays a vital role in defending against neuroinflammation. When exposed to different stimuli, microglia are activated and assume different phenotypes, participating in immune regulation of the nervous system and maintaining tissue homeostasis. The immunological activity of activated microglia is affected by glucose metabolic alterations. However, in the context of chronic neuroinflammation, specific alterations of microglial glucose metabolism and their mechanisms of action remain unclear. Thus, in this paper, we review the glycometabolic reprogramming of microglia in ND. The key molecular targets and main metabolic pathways are the focus of this research. Additionally, this study explores the mechanisms underlying microglial glucose metabolism reprogramming in ND and offers an analysis of the most recent therapeutic advancements. The ultimate aim is to provide insights into the development of potential treatments for ND.

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Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function

Cited by 10 publications

References 62 publications

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer’s Disease

Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation

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