Adding more concern to the reported increase in heavy alcohol consumption among adolescents is the emerging science regarding alcohol’s effect on the brain. This research just published in the Proceedings of the National Academy of Sciences elucidates the mechanism by which binge drinking damages the developing brain.

“Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis…”

The authors made a number of startling observations regarding the effect of alcohol on the brain’s center for short-term memory and adrenal regulation, the hippocampus:

“Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis…Alcohol significantly decreased the number of actively dividing type 1, 2a, and 2b cell types…suggesting that alcohol interferes with the division and migration of hippocampal preneuronal progenitors. Furthermore, the lasting alcohol-induced reduction in hippocampal neurogenesis paralleled an increase in neural degeneration mediated by nonapoptotic pathways.”

Yikes. The authors sum up their findings with these memorable comments:

“Altogether, these results demonstrate that the hippocampal neurogenic niche during adolescence is highly vulnerable to alcohol… This lasting effect, observed 2 mo after alcohol discontinuation, may underlie the deficits in hippocampus-associated cognitive tasks that are observed in alcoholics.”

A fascinating paper published last month in the Journal of Neuroscience now reveals how alcohol feeds an immune inflammatory attack on the brain:

“Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation.”

This is an extremely persuasive argument for moderation for anyone interesting in preserving brain health.

The authors go on to report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells by demonstrating that ‘turning off’ TLR4 prevents the neuroinflammatory brain damage:

“Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates…cytokine levels [interleukin (IL)-1β, tumor necrosis factor-{alpha}, IL-6] in the cerebral cortex,…TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.”

For us the main message is that excessive alcohol consumption fires up the brain’s glial cells (immune cells) and the resultant neuroinflammation does serious damage to the brain. This important research was highlighted in an editorial published last week in Science Translational Medicine which contains some notable comments:

“Ethanol is the most widely used psychotropic substance in the world, and chronic ethanol abuse leads to harmful changes in virtually every organ system in the body. Notably, this includes the brain, where consumption of alcohol can lead to irreversible changes in cognition, mood, and behavior. Although it has been known that this often involves degenerative, inflammatory-mediated processes, their precise nature has not been characterized. In a recent article, Alfonso-Loeches and colleagues report that much of the ethanol-induced inflammation in the brain depends on signaling through Toll-like receptors (TLRs). These receptors participate in innate immunity responses to infection but are also implicated in reactions to injury and degeneration in the brain.”

The editorial concludes with the compelling comparison of the brain damage done by activation by alcohol of neuroinflammation through Toll-like receptors with other common neurodegenerative conditions:

“These results suggest that TLRs play a critical role in alcohol-related brain changes, just as they have been previously implicated in Alzheimer’s disease, ischemic brain injury, and HIV infection.”

Besides curtailing excess and enjoying alcohol only in moderation we may be able to use coffee as protective therapy. There is abundant evidence of the benefit of coffee for the liver, including this recent study published in the journal Inflammation Research. The authors present data that:

“Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells… Furthermore, caffeine decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation and inhibited the necrosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α), whereas Kupffer cells from caffeine treatment mice produced less ROS and TNF-α.”

The authors conclude:

“These findings suggest that caffeine may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress and inflammatory response.”

Could this protective effect extend to the brain? There’s a lot of emerging evidence that suggests the answer is ‘yes’. Fascinating research published last month in the journal Experimental Neurology demonstrates that caffeine protects the brain from the kind of damage involved in Parkinson’s disease caused by pesticides:

“Environmental exposures suspected of contributing to the pathophysiology of Parkinson’s disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as…caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8 weeks.”

The data led to a conclusion that increases my enthusiasm for exercising the French press:

“Caffeine at 20 mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.”

As for Alzheimer’s disease, a supplemental issue of the Journal of Alzheimer’s Disease has no less than 22 papers on the benefits of caffeine for AD and other neurodegenerative disorders. I suggest you have a look, drink alcohol in moderation (or not at all if you prefer), and enjoy your coffee and tea if there are no contraindications.

With alcohol, as with so many other substances and stimuli, we can appreciate the principle of hormesis: a small amount may have benefit while a larger amount is harmful.

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A study just published in the journal Environmental Health Perspectives began with this observation: “Insecticides that target the nervous system may play a role in the development of childhood brain tumors (CBTs).” Naturally, as the authors note, there are significant genetic differences in the ability to metabolize such toxic chemicals. Indeed, they “observed strong interactions between genotype and insecticide exposure during childhood.” Their considerate conclusion: “Based on known effects of these variants, these results suggest that exposure in childhood to organophosphorus and perhaps to carbamate insecticides in combination with a reduced ability to detoxify them may be associated with CBT.”

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