Is TGR5 a therapeutic target for the treatment of spinal cord injury?

• Published in: Journal of neurochemistry Vol. 164; no. 4; pp. 454 - 467
• Main Authors: Smaling, Anna, Romero‐Ramírez, Lorenzo, Mey, Jörg
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2023
• Subjects: Animal models; Animals; Apoptosis; Bile; bile acid; Bile acids; Blood-brain barrier; Combinatorial analysis; Diet; Herbal medicine; Hydrogels; Inflammation; Lipid metabolism; Lipids; Models, Animal; Nervous system; Receptors, G-Protein-Coupled - physiology; Sensorimotor system; Spinal cord injuries; Spinal Cord Injuries - pathology; spinal cord injury; Stem cells; Taurochenodeoxycholic Acid - pharmacology; Taurochenodeoxycholic Acid - therapeutic use; Tauroursodeoxycholic acid; TGR5; Therapeutic targets; spinal cord injury; TGR5; apoptosis; bile acid; inflammation
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.15727

Bile acids, which are synthesized in liver and colon, facilitate the digestion of dietary lipids. In addition to this metabolic function, they also act as molecular signals with activities in the nervous system. These are mediated primarily by a G‐protein‐coupled bile acid receptor (known as TGR5). Preceded by a long tradition in Chinese medicine, bile acids are now being investigated as therapeutic options in several neuropathologies. Specifically, one bile acid, tauroursodeoxycholic acid (TUDCA), which passes the blood–brain barrier and shows anti‐inflammatory and anti‐apoptotic effects, has been tested in animal models of spinal cord injury (SCI). In this review, we discuss the evidence for a therapeutic benefit in these preclinical experiments. At the time of writing, 12 studies with TGR5 agonists have been published that report functional outcomes with rodent models of SCI. Most investigations found cytoprotective effects and benefits regarding the recovery of sensorimotor function in the subacute phase. When TUDCA was applied in a hydrogel into the lesion site, a significant improvement was obtained at 2 weeks after SCI. However, no lasting improvements with TUDCA treatment were found, when animals were assessed in later, chronic stages. A combination of TUDCA with stem cell injection failed to improve the effect of the cellular treatment. We conclude that the evidence does not support the use of TUDCA as a treatment of SCI. Nevertheless, cytoprotective effects suggest that different modes of application or combinatorial therapies might still be explored. This review discusses animal studies with bile acids to treat spinal cord injury (SCI). Treatment with tauroursodeoxycholic acid (TUDCA) produced cytoprotective effects and improved recovery in the subacute phase but had no lasting effects on sensorimotor functions. a Chemical formula of TUDCA; b rat spinal cord after SCI; c motor recovery in the subacute phase after contusion SCI; SCI‐control – treatment with saline, SCI‐TUDCA – treatment with two injections of 300 mg/kg TUDCA; *significant difference (p < 0.05) between TUDCA and saline‐treated groups, data from Wu et al. 2022.