SARS-CoV-2 infection causes dopaminergic neuron senescence, 2024, Yang et al.

SARS-CoV-2 infection causes dopaminergic neuron senescence
Liuliu Yang; Tae Wan Kim; Yuling Han; Manoj S. Nair; Oliver Harschnitz; Jiajun Zhu; Pengfei Wang; So Yeon Koo; Lauretta A. Lacko; Vasuretha Chandar; Yaron Bram; Tuo Zhang; Wei Zhang; Feng He; Chendong Pan; Junjie Wu; Yaoxing Huang; Todd Evans; Paul van der Valk; Maarten J. Titulaer; Jochem K.H. Spoor; Robert L. Furler O’Brien; Marianna Bugiani; Wilma D.J. Van de Berg; Robert E. Schwartz; David D. Ho; Lorenz Studer; Shuibing Chen

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction.

Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response.

High-throughput screening in hPSC-derived DA neurons identified several FDA approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients.

Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Highlights

• hPSC-derived DA neurons are susceptible to SARS-CoV-2 infection

• SARS-CoV-2 infection of DA neurons triggers cellular senescence response

• Several FDA-approved drugs were identified to rescue senescence of DA neurons

• Cellular senescence was found in substantia nigra tissues of COVID-19 patients

Link | PDF (Cell Stem Cell)

 

COVID’s toll on the brain: new clues emerge
https://www.nature.com/articles/d41586-024-00828-9

But how would molecules from the rest of the body influence inflammation in the brain? Research from neuroscientist Matthew Campbell and neurologist Colin Doherty at Trinity College Dublin has found that the blood–brain barrier, which separates the brain from the rest of the body, can break down during SARS-CoV-2 infection.

The team found that this barrier is more permeable in people with both long COVID and ‘brain fog’ — problems with memory, concentration and decision-making — than in uninfected people or people who have long COVID but not brain fog. The results, reported in Nature Neuroscience2, point to a clear route for immune molecules to enter the brain, where they could lead to brain fog.​

Given that other common viruses, like EBV, are known to invade the CNS, it couldn't cause MS otherwise, this could be a common mechanism to many of those symptoms. How do we get to understand this better? Many other pathogens, including bacteria, have been found in brains and elsewhere in the CNS, more often than not with the rabid insistence that they must be harmless, since they haven't been observed to cause "serious pathology". And they could sometimes be. H. pylori causes peptic ulcers, but most of the population carries it in their stomach with no ill effect. Same with MS, most people who contract mono will not develop MS.

I would bet that if a large-scale effort were made to find pathogens in the body, a lot more than expected would be found. And here it appears that the only way to find it is indirectly, since all they can usually find is the impact on blood vessels, and sometimes people had viral particles found in the brain who weren't considered to have LC or something like it.

I desperately hope that we can see AI forcing medicine into a new gear, because I just don't see the current systems being able to work out something as complex as this. Each piece takes years and it takes even more years to put the pieces together, all made even worse because of the supremacy that psychosomatic ideology has achieved in sabotaging all motivation. We are missing the necessary tools here.