TGR5 protects against pSNL-induced mechanical allodynia by alleviating neuroinflammation in the injured nerves of male mice DOI Creative Commons

Wenge Shi,

Yao Yao,

Yajing Liang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 12, 2024

Abstract Neuropathic pain is a pervasive medical challenge that currently lacks effective treatment solutions. Molecular changes occurring at the site of peripheral nerve damage contribute to development and central sensitization, which are critical components neuropathic pain. This study aimed investigate role G protein-coupled bile acid receptor (GPBAR1, also known as TGR5) in mechanisms underlying induced by partial sciatic ligation (pSNL) male mice. TGR5 was upregulated injured nerves colocalized predominantly with macrophages. Peri-sciatic administration TGR5-specific agonist INT-777 provided sustained relief from mechanical allodynia. Transcriptome sequencing revealed primarily attributable reduced neuroinflammation. finding corroborated reduction myeloid cells proinflammatory mediators (including CCL3, CXCL9, IL-6, TNF-α), accompanied an increase percentage anti-inflammatory M2 macrophages following administration. Furthermore, cell-specific knockdown pSNL exacerbated both allodynia substantiated data bulk RNA-seq expression levels inflammatory CCL2, TNF-α IL-1β), well increased monocytes/ nerve. Besides, activation microglia ipsilateral dorsal horn spinal cord altered when manipulated. In summary, TGR5, present nerves, plays protective offers potential target for treating

Язык: Английский

Emerging Roles of Bile Acids and TGR5 in the Central Nervous System: Molecular Functions and Therapeutic Implications DOI Open Access
Lorenzo Romero‐Ramírez, Jörg Mey

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9279 - 9279

Опубликована: Авг. 27, 2024

Bile acids (BAs) are cholesterol derivatives synthesized in the liver and released into digestive tract to facilitate lipid uptake during digestion process. Most of these BAs reabsorbed recycled back liver. Some progress other tissues through bloodstream. The presence central nervous system (CNS) has been related their capacity cross blood–brain barrier (BBB) from systemic circulation. However, expression enzymes receptors involved synthesis signaling, respectively, support hypothesis that there is an endogenous source with a specific function CNS. Over last decades, have tested as treatments for many CNS pathologies, beneficial effects. Although they were initially reported neuroprotective substances, also known reduce inflammatory processes. effects activation Takeda G protein-coupled receptor 5 (TGR5). This review addresses new challenges face BA research neuroscience, focusing on molecular functions. We discuss exogenous sources CNS, signaling TGR5 receptor, mechanisms action potential therapeutics neuropathologies.

Язык: Английский

Процитировано

2
NR1H4 ameliorates Parkinson’s disease via inhibiting astrocyte activation and neuroinflammation in a CEBPβ/NF-κB dependent manner DOI Creative Commons
Jingwen Li, Hanshu Liu, Xinyu Hu

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 142, С. 113087 - 113087

Опубликована: Сен. 5, 2024

Язык: Английский

Процитировано

1
TGR5 protects against pSNL-induced mechanical allodynia by alleviating neuroinflammation in the injured nerves of male mice DOI Creative Commons

Wenge Shi,

Yao Yao,

Yajing Liang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 12, 2024

Abstract Neuropathic pain is a pervasive medical challenge that currently lacks effective treatment solutions. Molecular changes occurring at the site of peripheral nerve damage contribute to development and central sensitization, which are critical components neuropathic pain. This study aimed investigate role G protein-coupled bile acid receptor (GPBAR1, also known as TGR5) in mechanisms underlying induced by partial sciatic ligation (pSNL) male mice. TGR5 was upregulated injured nerves colocalized predominantly with macrophages. Peri-sciatic administration TGR5-specific agonist INT-777 provided sustained relief from mechanical allodynia. Transcriptome sequencing revealed primarily attributable reduced neuroinflammation. finding corroborated reduction myeloid cells proinflammatory mediators (including CCL3, CXCL9, IL-6, TNF-α), accompanied an increase percentage anti-inflammatory M2 macrophages following administration. Furthermore, cell-specific knockdown pSNL exacerbated both allodynia substantiated data bulk RNA-seq expression levels inflammatory CCL2, TNF-α IL-1β), well increased monocytes/ nerve. Besides, activation microglia ipsilateral dorsal horn spinal cord altered when manipulated. In summary, TGR5, present nerves, plays protective offers potential target for treating

Язык: Английский

Процитировано

0