GLP-1(7-36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

Mol Biol Rep. 2024 Feb 19;51(1):313. doi: 10.1007/s11033-024-09244-8.

Abstract

Background: Glucagon-like peptide-1 (GLP-1) (7-36) amide, an endogenous active form of GLP-1, has been shown to modulate oxidative stress and neuronal cell survival in various neurological diseases.

Objective: This study investigated the potential effects of GLP-1(7-36) on oxidative stress and apoptosis in neuronal cells following traumatic brain injury (TBI) and explored the underlying mechanisms.

Methods: Traumatic brain injury (TBI) models were established in male SD rats for in vivo experiments. The extent of cerebral oedema was assessed using wet-to-dry weight ratios following GLP-1(7-36) intervention. Neurological dysfunction and cognitive impairment were evaluated through behavioural experiments. Histopathological changes in the brain were observed using haematoxylin and eosin staining. Oxidative stress levels in hippocampal tissues were measured. TUNEL staining and Western blotting were employed to examine cell apoptosis. In vitro experiments evaluated the extent of oxidative stress and neural apoptosis following ERK5 phosphorylation activation. Immunofluorescence colocalization of p-ERK5 and NeuN was analysed using immunofluorescence cytochemistry.

Results: Rats with TBI exhibited neurological deterioration, increased oxidative stress, and enhanced apoptosis, which were ameliorated by GLP-1(7-36) treatment. Notably, GLP-1(7-36) induced ERK5 phosphorylation in TBI rats. However, upon ERK5 inhibition, oxidative stress and neuronal apoptosis levels were elevated, even in the presence of GLP-1(7-36).

Conclusion: In summary, this study suggested that GLP-1(7-36) suppressed oxidative damage and neuronal apoptosis after TBI by activating ERK5/CREB.

Keywords: Apoptosis; Glucagon-like peptide-1; Hippocampal CA fields; Oxidative stress; Traumatic brain injury.

MeSH terms

  • Animals
  • Apoptosis
  • Brain Injuries, Traumatic* / drug therapy
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disease Models, Animal
  • Glucagon-Like Peptide 1* / pharmacology
  • Glucagon-Like Peptide 1* / therapeutic use
  • Hippocampus
  • Male
  • Mitogen-Activated Protein Kinase 7 / drug effects
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Glucagon-Like Peptide 1
  • Neuroprotective Agents
  • Peptide Fragments
  • Mitogen-Activated Protein Kinase 7
  • Creb1 protein, rat
  • Cyclic AMP Response Element-Binding Protein