Neuro‐inflammation induced in the hippocampus of ‘binge drinking’ rats may be mediated by elevated extracellular glutamate content

Abstract

The neuropathological and immune changes induced in the brain by ‘binge drinking’ have been investigated in a rat model. Evidence of neuro‐inflammation was identified in the ‘binge drinking’ rat model of alcohol abuse after 3 weeks of administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two consecutive days, followed by 5 days of abstinence: Firstly, alveolar macrophages, isolated from these animals, showed significant increases in inducible nitric oxide synthase, as assayed by nitrite release, both before and after lipopolysaccaharide stimulation. Secondly, significant numbers of activated microglia were present in the dentate gyrus region of the hippocampus of the ‘binge drinking’ model, after major histocompatibility complex class II staining, by comparison with the control. Microdialysis studies in the ventral hippocampus identified a significant increase in the basal extracellular concentration of glutamate, in both the 2 and 3 g/kg administered ‘binge drinking’ rats. In contrast, no changes in the hippocampal extracellular concentrations, of GABA and taurine, or the dopamine and serotonin metabolites were observed under basal conditions. A further dose of EtOH induced a significant decrease in the concentrations of both 3,4‐dihydroxyphenylacetic acid and 5‐hydroxyindoleacetic acid, whereas glutamate, taurine and GABA levels were unaffected. There was no evidence that EtOH preference was initiated by the ‘binge drinking’ regimen. Our results suggest that the possible toxicity associated with ‘binge drinking’ maybe directed by the elevated glutamate levels, which in turn, activate phagocytic cells to release their inflammatory cytokines and chemokines, ultimately leading to neuro‐inflammation.

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

“…At the production conditions used here (15.000 IMA/cm 2 ), we examined whether the composition of conditioned medium changed drastically. As elevated extracellular L-glutamate (L-Glu) content has been reported in previous inflammation models (Castillo et al 2002;Ward et al 2009), we also investigated whether this could be the cause of neurotoxicity in our model. Amino acid analysis showed that cytokine-conditioned medium differed for few amino acids from control supernatant, but many constituents, including L-Glu, remained largely unchanged (Fig.…”

Lifetime Alcohol Intake, Binge Drinking Behaviors, and Breast Cancer Risk

“…Additionally, experimental studies demonstrate that binge drinking increases inflammation levels as well as insulin resistance (9,10). Inflammation and insulin resistance are hypothesized to be key biological mechanisms for the development of cancer, and thus binge drinking could be particularly relevant for breast cancer risk (11).…”

Ethanol intake-induced apoptosis in glial cells and axonal disorders in the cerebellar white matter of UChA rats (voluntary ethanol consumers)

“…The ethanol intoxication causes an increase in the microglial biomarkers (Crews et al, 2006;He and Crews, 2008;Ward et al, 2009) which can be activated in a neuroprotective way (Zhao et al, 2012), lastly reducing the apoptotic damage (Lalancette-Hebert et al, 2007). Our study provides evidence that the chronic ethanol intake can cause apoptotic responses in the glial cells leading to a microenvironmental imbalance, and consequently allowing the axons to be severely affected by degradation because of slow axonal transmission and low neuronal capacity.…”