Effects of novel GLT-1 modulator, MC-100093, on neuroinflammatory and neurotrophic biomarkers in mesocorticolimbic brain regions of male alcohol preferring rats exposed chronically to ethanol

Brain Res Bull. 2024 Apr 1:110935. doi: 10.1016/j.brainresbull.2024.110935. Online ahead of print.ABSTRACTChronic ethanol consumption can lead to increased extracellular glutamate concentrations in key reward brain regions, such as medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), and consequently leading to oxidative stress and neuroinflammation. Previous studies from our lab tested β-lactam antibiotics and novel β-lactam non-antibiotic, MC-100093, and showed these β-lactam upregulated the major astrocytic glutamate transporter, GLT-1, and consequently reduced ethanol intake and normalized glutamate homeostasis. This present study tested the effects of novel synthetic β-lactam non-antibiotic drug, MC-100093, in chronic ethanol intake and neuroinflammatory and trophic factors in subregions of the NAc (NAc core and shell) and mPFC (Prelimbic, PL; and Infralimbic, IL) of male P rats. MC-100093 treatment reduced ethanol intake after 5-week drinking regimen. Importantly, MC-100093 attenuated ethanol-induced downregulation of brain derived neurotrophic factor (BDNF) expression in these brain regions. In addition, MC-100093 attenuated ethanol-induced upregulation of pro-inflammatory cytokines such as TNF-a and HMGB1 in all these brain regions. Furthermore, MC-100093 treatment attenuated ethanol-induced increase in RAGE in these brain regions. MC-100093 prevented neuroinflammation caused by ethanol intake as well as increased neurotrophic factor in mesocorticolimbic b...

Source: Brain Research - April 3, 2024 Category: Neurology Authors: Shelby Travaglianti Ahmed Alotaibi Woonyen Wong Magid Abou-Gharbia Wayne Childers Youssef Sari Source Type: research