2023-10-18 14:55:55
What links Long Covid and the ‘good mood hormone’? After the pandemic, understanding the mechanism that triggers post-infection sequelae remains the global health challenge on which various groups of scientists are focusing their efforts. One of these teams calls serotonin into question – or rather a reduction thereof – as a possible explanation for the persistent concentration difficulties, attention and memory problems and other, often debilitating, symptoms associated with Long Covid. The hypothesis formulated by the authors of the study published in ‘Cell’, and also cited in ‘Science’ online, is that the inflammation triggered in response to the Sars-CoV-2 virus causes a decrease in serotonin – which among the various functions is that it is the ‘chemical messenger’ involved in regulating mood and digestion – and that this decline in turn causes cognitive problems.
I study
The scientific work has as its starting point an observation by Penn Medicine researchers: people who attended a clinic dedicated to post-Covid had lower levels of serotonin in their blood than people who had completely recovered from the infection. Patients with acute Covid also showed this reduction in serotonin in the blood. The researchers wondered whether viral infection could lower levels of this substance. Even more so since some previous studies had already hinted at a link between serotonin levels and post-Covid symptoms (although other research did not show such an association). To verify what they observed, the team infected mice with Sars-CoV-2 or injected them with a drug that stimulates a similar inflammatory response.
Both treatments caused a drop in serotonin in the blood, said study co-author Maayan Levy, a microbiologist at the University of Pennsylvania’s Perelman School of Medicine. “We – explains the team in the study – propose a mechanism that links 4 hypotheses in a single pathway and provides useful information for therapeutic interventions. Viral infection and inflammation driven by type I interferon reduce serotonin through three mechanisms: decreased intestinal absorption of the serotonin precursor, tryptophan; platelet hyperactivation and thrombocytopenia, which affect serotonin storage; and increased serotonin turnover mediated by Mao (monoamine oxidase)”. Peripheral serotonin reduction, “in turn, impedes vagus nerve activity and thus impairs hippocampal responses and memory. These findings provide a possible explanation for the neurocognitive symptoms associated with viral persistence in Long Covid, which may extend to other post-virus syndromes”.
What happen
In other words, what happens is that in the mouse intestine the absorption of dietary tryptophan, a chemical precursor of serotonin present in many foods, including fish and dairy products, is hindered. And the transport of the molecule through platelets into the bloodstream is also compromised. Finally, the activity of an enzyme that breaks down serotonin also appears to be enhanced. These three factors together cause peripheral serotonin levels to be reduced. The researchers linked these changes to the mice’s performance on memory tests. The team inserted objects such as glue sticks and paper clips into the cages, and then added a new object. Because mice prefer novelty, animals with better memories tend to lose interest in familiar objects more quickly. The team found that mice treated with viruses or inflammation-stimulating drugs showed worse recall, and analyzes of their brain tissue revealed reduced activity in the hippocampus.
Researchers could reverse this deterioration by supplementing the animals’ diets with tryptophan or by giving them the antidepressant fluoxetine, a selective serotonin reuptake inhibitor that is believed to work primarily by increasing serotonin levels in the brain. However, no differences were found between treated and untreated mice in brain serotonin levels, only blood serotonin. Other scientists, commenting on the study, note that the work is based mainly on experiments on mice, and that it leaves several questions open.
Co-author Christoph Thaiss, Perelman School of Medicine, says the findings suggest that a reduction in this “peripheral” serotonin circulating outside the brain and spinal cord affects the hippocampus triggering the cascade effect described. An expert from another university, Jeffrey Meyer, a neuroscientist at the University of Toronto, is not convinced that the reduction of peripheral serotonin can explain the patients’ symptoms. However, he adds, the discovery of a reduction in tryptophan could be “interesting and relevant for Long Covid”. It is important to remember that there are probably multiple types of Long Covid, driven by different root causes, finally observes Akiko Iwasaki, immunobiologist at the Yale School of Medicine. A low serotonin level may define a particular type, she says, although more work is needed to know how this might cause cognitive symptoms.
#Long #Covid #memory #loss