Liraglutide is neurotrophic and neuroprotective in neuronal cultures and mitigates mild traumatic brain injury in mice. (18th June 2015)

• Record Type: Journal Article
• Authors: Li, Yazhou; Bader, Miaad; Tamargo, Ian; Rubovitch, Vardit; Tweedie, David; Pick, Chaim G.; Greig, Nigel H.
• Is Part Of: Journal of neurochemistry. Volume 135:Number 6(2015:Dec.)
• Page Start: 1203
• Page End: 1217
• Publication Date: 2015-06-18
• Subjects: apoptosis -- cAMP‐response element binding protein -- glucagon‐like peptide‐1 -- liraglutide -- neuroprotection -- traumatic brain injury; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13169
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Traumatic brain injury (TBI), a brain dysfunction for which there is no present effective treatment, is often caused by a concussive impact to the head and affects an estimated 1.7 million Americans annually. Our laboratory previously demonstrated that exendin‐4, a long‐lasting glucagon‐like peptide 1 receptor (GLP‐1R) agonist, has neuroprotective effects in cellular and animal models of TBI. Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP‐1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose‐dependent proliferation in SH‐SY5Y cells and in a GLP‐1R over‐expressing cell line at reduced concentrations. Pre‐treatment with liraglutide rescued neuronal cells from oxidative stress‐ and glutamate excitotoxicity‐induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin‐4 in vitro . The cAMP/PKA/pCREB pathway appears to play an important role in this neuroprotective activity of liraglutide. Furthermore, our findings in cell culture were well‐translated in a weight drop mTBI mouse model. Post‐treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI when evaluated 7 and 30 days post trauma. These data cross‐validate former studies of exendin‐4 and suggest that liraglutide holds therapeutic potential for the treatment of mTBI. Exendin‐4, a long‐lasting glucagon‐like peptide 1 receptor (GLP‐1R) agonist, has neuroprotective effects in cellular and animal models of traumatic brain injury (TBI). Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP‐1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose‐dependent proliferation in SH‐SY5Y cells and in a GLP‐1R over‐expressing cell line at reduced concentrations. Pretreatment with liraglutide rescued neuronal cells from oxidative stress‐ and glutamate excitotoxicity‐induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin‐4 in vitro, likely involving the cAMP/PKA/pCREB pathway. Our findings in cell culture were well‐translated in a weight‐drop mTBI mouse model. Post‐treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI. Abstract : Exendin‐4, a long‐lasting glucagon‐like peptide 1 receptor (GLP‐1R) agonist, has neuroprotective effects in cellular and animal models of traumatic brain injury (TBI). Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP‐1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose‐dependent proliferation in SH‐SY5Y cells and in a GLP‐1R over‐expressing cell line at reduced concentrations. Pretreatment with liraglutide rescued neuronal cells from oxidative stress‐ and glutamate excitotoxicity‐induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin‐4 in vitro, likely involving the cAMP/PKA/pCREB pathway. Our findings in cell culture were well‐translated in a weight‐drop mTBI mouse model. Post‐treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI. Read the Editorial Highlight for this article on page 1059 .