Authors : Manal A. Othman, Raouf Fadel, Yasin Tayem, Ahmed Jaradat, Aisha Rashid, Ayesha Fatima, Ali E. Al-Mahameed, Wael Amin Nasr El-Din
DOI : 10.1007/s00441-022-03735-5
Volume : 392
Issue : 2
Year : 2023
Page No : 443-466
Type 2 diabetes (T2D) is implicated in the injury of several organs, including the brain resulting in neuronal damage, which may lead to cognitive impairment and dementia. Additionally, it is linked to inflammation, cytokine release, apoptosis and various degenerative conditions. Astrocytes and microglia might have a role in mediating these processes. Caffeine, a psychoactive beverage, has been shown to reduce the risk of cognitive and memory impairment. This study proposes anti-inflammatory and anti-apoptotic role of caffeine, which can be mediated via microglia/astrocyte activation and overexpression of pro-inflammatory molecules. T2D was induced in rats by feeding with high fat high sugar diet and injecting a single low dose streptozotocin (STZ) intraperitoneally. Other diabetic rats were given caffeine orally (in two doses) for 5 weeks, starting 1 week before STZ injection. Measurement of plasma cytokines, TNFα and IL6, was performed using enzyme-linked immunosorbent assay (ELISA) technique. After sacrificing animals, brains were obtained and processed for histological evaluation. Immunohistochemistry was also performed using the following primary antibodies, anti-astrocyte marker GFAP, anti-microglia marker CD11b and apoptotic marker (anti-cleaved caspase-3). There was upregulation of IL6 and TNF-α in diabetic rats. Additionally, histological evaluation of the hippocampus of diabetic rats revealed cellular degeneration. There was increased immunostaining of GFAP, CD11b and cleaved caspase-3 in diabetic rats. Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner. In conclusion, caffeine had an ameliorative role in enhancing hippocampal degenerative changes in T2D.