We have located links that may give you full text access.
Novel mechanism of action for the mood stabilizer lithium.
Bipolar Disorders 2020 October 10
BACKGROUND: Bipolar Disorder (BD) is associated with a decrease in cellular resilience. Despite the half a century old discovery of lithium's efficacy for the treatment of BD, its exact mechanisms remain elusive. Accumulating data suggest that lithium's cytoprotective properties involve the modulation of several UPR proteins, such as GRP78. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum resident protein that regulates proteostasis through directly interacting with GRP78. The purpose of this study was to determine whether lithium increases MANF expression using cellular and rodent models and, if so, to elucidate the cellular mechanisms of action.
PROCEDURE: Mouse striatal neuroblasts were treated with PBS, lithium, or lithium + Activator Protein-1 (AP-1) inhibitor for 24-72 hours. Once cells were harvested, mRNA was extracted. In vivo experiments included, intraperitoneal injections of lithium or saline to male Sprague Dawley rats twice daily for 14 consecutive days. Following drug treatment, brain tissue was isolated, and mRNA was extracted from various regions. MANF gene expression was measured using RT-qPCR.
RESULTS: In vitro studies showed lithium-treated cells displayed a significant increase in MANF mRNA expression compared to controls. In contrast, cells treated with lithium and AP-1 inhibitor showed no increase in expression. Similarly, in vivo studies revealed that lithium-treated rats compared to controls had a significant increase in MANF expression in the PFC and striatum.
CONCLUSION: Taken together, these data suggest that lithium's therapeutic mechanism involves the maintenance of ER homeostasis via increased MANF gene expression mediated by the AP-1 transcription factor.
PROCEDURE: Mouse striatal neuroblasts were treated with PBS, lithium, or lithium + Activator Protein-1 (AP-1) inhibitor for 24-72 hours. Once cells were harvested, mRNA was extracted. In vivo experiments included, intraperitoneal injections of lithium or saline to male Sprague Dawley rats twice daily for 14 consecutive days. Following drug treatment, brain tissue was isolated, and mRNA was extracted from various regions. MANF gene expression was measured using RT-qPCR.
RESULTS: In vitro studies showed lithium-treated cells displayed a significant increase in MANF mRNA expression compared to controls. In contrast, cells treated with lithium and AP-1 inhibitor showed no increase in expression. Similarly, in vivo studies revealed that lithium-treated rats compared to controls had a significant increase in MANF expression in the PFC and striatum.
CONCLUSION: Taken together, these data suggest that lithium's therapeutic mechanism involves the maintenance of ER homeostasis via increased MANF gene expression mediated by the AP-1 transcription factor.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app