Science Sub-Journal: Reveals that drinking alcohol causes small glial cells to devour and trim synapses, triggering anxiety.

!--webeditor:page title" -- --- Alcohol abuse (also translated as alcoholism) is associated with pathophysiological changes in the brain and exosynia organs, many of which can lead to life-threatening conditions.
effects of alcohol on the central nervous system (CNS) often lead to behavioural impairments (including anxiety, cognitive decline and motor dysfunction) and impaired synapses.
synapse function is a major feature of alcohol abuse and may be the basis for such behavioral defects.
alcohol has an adverse effect on the secretion/recycling of synactal front and synnapse chambers, as well as neurotransmitters, which eventually leads to the destruction of excitability and inhibitory nerve transfer.
harmful effects of alcohol on synapses may be attributed to the well-known effects of alcohol on neurons, or to the under-aware effects of alcohol on glial cells.
Small glial cells are the main group of innocular immune cells in the brain that maintain the dynamic balance of nerve tissue and monitor the essence of CNS by continuously extending and retracting their cell protrusions, monitoring tissue damage or infection, and examining the functional state of synapses.
when CNS tissue is damaged or infected, small glial cells are activated, changing their morphology (turning into amoeba-like shapes), phagocytosis, and transcriptional characteristics to restore tissue stability.
However, in many neuropsymatological disorders, the impaired immune function of small glial cells often leads to excessive production of inflammatory media and increased phagocytosis activity, which can be harmful to synapses and have a negative impact on behavior.
in animal models of alcoholism and alcoholism, changes in the function of small glial cells are associated with neuroimmune activation and may be directly related to certain neurotoxicity and bad behavior in alcohol intake.
activation of the innate immune system helps to adapt to nerves in brain regions associated with increased alcohol intake, tolerance, dependence and recurrence.
Consistent with the neuroimmune hypothesis of alcohol addiction, knocking out multiple genes involved in the immune response reduces voluntary alcohol intake in mice;
In a new study, researchers from the University of Porto in Portugal found that in male mice, drinking alcohol for 10 consecutive days (on average, a person drinks about five times a day for humans) enhanced Src-TNF signal transductivity in small glial cells in the pre-cortical cortical cortical layer, enhancing their swallowing capacity and leading to abnormal synaptic pruning, which ultimately led to synaptic loss and anxiety-like behavior.
, these results suggest that abnormal synhapus pruning of small glial cells may play an important role in synactical delivery defects caused by alcohol abuse.
study was published in the September 22, 2020 issue of the Journal of Science Signaling under the title "Daily alcohol triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior."
authors of the paper are Renato Socodato, Teresa Sumavielle and João B. Relvas of the University of Porto.
is thought to be a major factor in brain damage caused by alcohol. Several previous studies of
, including 20 weeks of alcohol consumption in 5-week-old female mice with an ethanol concentration of approximately 140 mg/dl, and 5 weeks of liquid diet with ethanol concentration of approximately 215 mg/dl in female mice between 6 and 8 weeks of age, have shown that heavy drinking triggers inflammatory cytokine expression characteristics, accompanied by neuroglial growth.
However, although repetitive drinking levels induced neuroimmune activation and inflammatory synapse loss, in the new study, the authors found that in male mouse models, this did not produce classic inflammatory cytokine expression.
Instead, their data were more in line with previous transcriptional histological studies, particularly an RNA sequencing study: long-term exposure of small glial cells from the pre-frontal cortical cortical layer to alcohol (using a two-bottle selection pattern the next day) did not induce typical inflammatory cytokine expression characteristics.
Similarly, in the ethanol exposure model developed by the authors, transcriptional expression of TLR4 decreased significantly, which was more consistent with a previous study that showed that acute exposure to alcohol in in-body cultured human perveloped blood monocytes inhibited TLR4 signal transducation.
, the dose and duration of ethanol exposure appear to affect neuroimmune activation and small glial cell-promoting signal transductivity in different ways.
In this new study, Gene Ontology analysis of pathogenic abundance shows that ethanol intake, also known as alcohol, induces TLR2 and inflammatory cytokine TNF expression, and that these pathways may be co-regulated in small glial cells.
's TLR2-dependent recruitment and activation of Src kinase stimulates several immune-related pathways in small glial cells, including NF-B activation, binding of phospholipidase C to an integrator, reactive oxygen production, the production of lecithin 12 (IL-12) and, ultimately, the production of inflammatory media, including TNF.
ethanol enhances Src's activity, leading to a nuclear trans-position of p65 sub-base in the NF-B complex, which eventually leads to the production and secretion of NF-B-dependent TNF in small glial cells.
similar to the effect of blocking TNF with pomalidomide (PMD), inhibiting Src with AZD0530, a clinically relevant Src inhibitor, can also prevent small glial cell growth.
Src inhibitor also inhibits anxiety-like behavior caused by ethanol intake, suggesting that targeting the Src-NF-B-TNF pathway in small glial cells may prevent the anxiety-causing effects of alcohol.
the exact signal transducting mechanism of small glial cell Src activation and NF-B dependent transcription caused by alcohol exposure is worth further study.
Similarly, although the authors' small glial cell ablation experiments showed that small glial cells were the primary producers of TNF in the pre-preleteal cortical cortical layer during ethanol exposure, they could not rule out that the TNF produced by external organs (such as the liver) or even astrocytes in response to ethanol exposure may also contribute to their observed small glial cell esophation.
!--/ewebeditor:page--!--ewebeditor:page title="--the pre-pre-cortical cortical layer contains glutamate-energy excitable neurons that locally form synapses or far-end projections to the cortical and lower cortical layers.
the inability to establish and maintain proper excitability connections can lead to an imbalance in neuron activity throughout the network, which may at least explain some of the behavioral defects found in multiple neurological disorders.
Thus, the loss of excitable synapses in the pre-cortical cortical layer caused by ethanol may be sufficient to disrupt the excitation/inhibition balance of the pre-presteal cortical neurons projected into the anxiety-related centers of the lower cortical region, suggesting that the loss of ethanol-induced pre-cortical synapses may directly affect alcohol-related anxiety.
while this is reasonable, the authors' data do not formally rule out the possibility that small glial cells can be activated directly in other brain regions, such as the amygdala, to trigger an anxiety-promoting effect of ethanol.
anxiety is also associated with alcohol withdrawal.
However, given that the authors' behavioral analysis was conducted at a time when ethanol levels in mice were expected to be 100 to 120 mg/dl, the increase in anxiety-like behavior they observed may reflect a sustained increase in ethanol intake rather than alcohol-induced anxiety leading to a more persistent state of anxiety.
note that the esolyses observed in this study were reported only in male mice.
differences in emotional responses in mice, such as those associated with anxiety-like behavior, are well documented and may be associated with changes in sexual hormone levels during the emotional cycle.
The transcription of glial cells in female mice and glial cells in male mice is also very different, and the fact that female mice are more likely to develop alcohol-related inflammation and neuron damage suggests that further research is needed using female mice to better understand the effects of ethanol exposure on small glial cell-dependent synhapl pruning, synhap function, and anxiety-related behavior.
alcohol intake allows small glial cells to trim synapses, pictured is Science Signaling, 2020, doi:10.1126/scisignal.aba5754.
small glial cells participate in synactal remodeling by devouring synth endings.
the new study, the authors found that ethanol exposure may increase the phagocytosty of small glial cells by enhancing their ability to devour synth structures.
In contrast, ethanol reduces the phagocytosis of small glial cells on E. coli and amyloid proteins, and also inhibits the phagocytosis of small glial cells triggered by P2X4 subject activation, suggesting that ethanol may alter the ability of small glial cells to devour depending on the circumstances.
In addition, given the significant differences in the removal activity of small glial cells between different brain regions, it is conceivable that small glial cells in the pre-frontal cortical cortical layer are more likely to devour and trim synapses than small glial cells in the hippocellus after exposure to alcohol.
While further in-depth research is needed to identify the exact mechanisms that cause these regional differences and the heterogeneity of small glial cells, the authors found that small glial cells can devour the synaptic back chamber in the pre-cortical cortical layer, providing important new evidence on how the brain's immune system causes damage to synaptic transmission, a major harmful consequence of alcohol abuse.
(bioon.com) Reference: Renato Socodato et al. Daily alcohol triggers aberrant synaptic pruning leads to synapse loss and anxiety-like behavior. Science Signaling, 2020, doi:10.1126/scisignal.aba5754.!--/ewebeditor:page--.