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Review
. 2023 Jul;43(5):1885-1904.
doi: 10.1007/s10571-022-01308-2. Epub 2022 Nov 27.

Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration

Surendra Kumar Anand  1 , Mir Hilal Ahmad  1 , Manas Ranjan Sahu  1 , Rhea Subba  1 , Amal Chandra Mondal  2
Affiliations
Review

Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration

Surendra Kumar Anand et al. Cell Mol Neurobiol. 2023 Jul.

Abstract

Alcohol consumption is known to cause several brain anomalies. The pathophysiological changes associated with alcohol intoxication are mediated by various factors, most notable being inflammation. Alcohol intoxication may cause inflammation through several molecular mechanisms in multiple organs, including the brain, liver and gut. Alcohol-induced inflammation in the brain and gut are intricately connected. In the gut, alcohol consumption leads to the weakening of the intestinal barrier, resulting in bacteria and bacterial endotoxins permeating into the bloodstream. These bacterial endotoxins can infiltrate other organs, including the brain, where they cause cognitive dysfunction and neuroinflammation. Alcohol can also directly affect the brain by activating immune cells such as microglia, triggering the release of pro-inflammatory cytokines and neuroinflammation. Since alcohol causes the death of neural cells, it has been correlated to an increased risk of neurodegenerative diseases. Besides, alcohol intoxication has also negatively affected neural stem cells, affecting adult neurogenesis and causing hippocampal dysfunctions. This review provides an overview of alcohol-induced brain anomalies and how inflammation plays a crucial mechanistic role in alcohol-associated pathophysiology.

Keywords: Adult neurogenesis; Alcohol intoxication; Neurodegeneration; Neuroinflammation; Toxicity.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1
Fig. 1
Systematic representation of alcohol-induced inflammation-mediated gut dysbiosis, liver cirrhosis, neurodegeneration, and other brain deformities. Alcohol intoxication results in disruption of the gut epithelial barrier, which causes a leaky gut. This leakage results in the infiltration of bacteria and bacterial endotoxins into the blood circulation resulting in systemic inflammation. The bacteria and endotoxins like Lipopolysaccharides (LPS) cross the blood–brain barrier and activate Toll-like receptor (TLR) signaling cascades. Stimulation of TLRs downstream activation of the transcription factors that induce pro-inflammatory gene expressions, neuroinflammation and neuronal death
Fig. 2
Fig. 2
Proposed mechanism of alcohol-mediated inhibition of NSC activity. Adult neurogenesis occurs in several steps, namely proliferation of NSCs, migration of neuroblasts and differentiation into new neurons. If the new neurons survive, they are integrated into the existing neural circuitry. Alcohol is known to negatively affect NSCs proliferation and new neuron survival. Here, we propose that alcohol may exert its effects by activation of microglia and release of pro-inflammatory cytokines such as TNF-α and IFN-γ, both of which are known to inhibit NSCs proliferation
See this image and copyright information in PMC

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