Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder

Abstract

Alcohol use disorder is a pervasive and detrimental condition that involves changes in neuroplasticity and neurogenesis. Alcohol activates the neuroimmune system and alters the inflammatory status of the brain. Tumour necrosis factor (TNF) is a well characterised neuroimmune signal but its involvement in alcohol use disorder is unknown. In this review, we discuss the variable findings of TNF's effect on neuroplasticity and neurogenesis. Acute ethanol exposure reduces TNF release while chronic alcohol intake generally increases TNF levels. Evidence suggests TNF potentiates excitatory transmission, promotes anxiety during alcohol withdrawal and is involved in drug use in rodents. An association between craving for alcohol and TNF is apparent during withdrawal in humans. While anti-inflammatory therapies show efficacy in reversing neurogenic deficit after alcohol exposure, there is no evidence for TNF's essential involvement in alcohol's effect on neurogenesis. Overall, defining TNF's role in alcohol use disorder is complicated by poor understanding of its variable effects on synaptic transmission and neurogenesis. While TNF may be of relevance during withdrawal, the neuroimmune system likely acts through a larger group of inflammatory cytokines to alter neuroplasticity and neurogenesis. Understanding the individual relevance of TNF in alcohol use disorder awaits a more comprehensive understanding of TNF's effects within the brain.

Novel paradigms for the gut–brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder

“…Some of these correlations of cytokine levels and the arrangement of gut permeability factors coincide with our earlier observations of hyperhomocysteinemia, gut dysfunctions, and markers of excessive drinking (21). As reflected by the alterations in blood markers, these intestinal changes also lead to behavioral changes that could correspondingly be observed with the severity of alcohol abuse (7,8,62). In our study, we found that the derangement of gut-permeability factors and the role of proinflammatory cytokines constituted the gutbrain axis of AUD.…”

Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients

“…In our study, TNF-α (which was not significantly different from AUD patients without withdrawal 43 , Table 2) and HDD90 were associated in AUD patients exhibiting withdrawal. This supports the unique characterization of proinflammatory activity with a heavy drinking marker indicating a relationship with alcohol-associated neuroinflammation 44,45 , leading to or contributing in withdrawal 11 . We could identify a three compartment response system that could be involved in characterizing the gut-brain axis for any of the domains that we studied.…”

Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

“…Perhaps this is why there is not a relationship between BrdU+ cell number and withdrawal severity ( Table 3 ) as there is in males ( Nixon and Crews, 2004 ). Indeed, there are known sex differences in several events surrounding alcohol-induced damage, such as neuroimmune activation ( Wilhelm et al, 2016 ; Barton et al, 2017 ; Rath et al, 2020 ), effects of which notably also interact with the control of adult neurogenesis ( Alvarez Cooper et al, 2020 ; Diaz-Aparicio et al, 2020 ).…”