What’s In Your Brain?

I am going to mention COVID only briefly today to point out how the virus has lost its mojo with respect to the general bulk of the population. The situation is a far cry from 2020 and 2021 when the vaccines made a tremendous impact in reducing critical illness and death for the high risk population. The recent CDC tables highlight that any predicted summer wave of COVID has yet to begin, and that the virus now accounts for the lowest number of hospitalizations per 100,000 people since the Pandemic initially ramped up. It looks right now like the risk of hospitalization from COVID for generally healthy folks is running on par with getting hit by lightening while scuba diving. Certainly lots of people are still catching COVID, but accumulated immunity has turned it into just another pesky upper respiratory illness that few people are testing for. That community-wide immunity barrier also helps protect the people with immune defects or other very significant co-morbidities, since there are fewer potential encounters with the virus, and it’s likely that ill people are secreting less virus and for shorter periods of time.

Let’s move on to one of my favorite parasites—there are so many fascinating critters that it is hard to choose. Toxoplasma gondii is a unicellular parasite of a wide host range of mammals, birds and humans. When I first learned about it in medical school, we were taught that the initial infection might be somewhat symptomatic; but assuming you had a fairly normal immune system, these parasites which especially like to disseminate from the initial introduction in the GI tract to your nervous system and brain, would be completely controlled and quiescent for your lifetime. If you were unlucky enough to acquire a significant insult to the immune system, say HIV infection, or drug-induced immune suppression needed for the treatment of a variety of diseases or transplantation, then those inert toxoplasma cysts could reactivate and begin destroying your brain, spinal cord, or retina. I often wondered if those supposedly inert cysts of toxoplasmosis truly did nothing at all—I suppose I just didn’t fancy the idea of other residents in my brain, since I do enjoy a nice steak tartare. You probably know that this infection is acquired by intentionally ingesting undercooked (raw) meat, or unintentionally ingesting toxoplasma cysts in the feces of cats. If you are thinking this must be a pretty rare infection, that’s not correct, 10-30% of humans around the world are infected, with about an 11% rate in the US. That translates to an estimated 1000-4000 fetuses infected in the US every year, which can happen when the mother acquires the infection for the first time during pregnancy. The outcomes for the fetus can be devastating.

Observational studies have found that persons with schizophrenia have statistically higher rates of toxoplasmosis infection compared to matched groups without this mental disorder. That is determined simply by looking for the presence or absence of antibodies in the blood. Other studies have found an association of higher rates of schizophrenia and other mental disorders in children raised in households with outdoor cats than children from a cat free environment. Cats allowed outdoors are, of course, more likely to acquire toxoplasmosis through their hunting behaviors. Other published studies have found that individuals with toxoplasma infection are judged to be more attractive to the opposite sex, and that women with the infection have statistically lower BMI (body mass index), and a higher number of lifetime sex partners. If that’s not a reason to go out to the pet store and purchase a kitty I don’t know what is. Now these studies are all association with no inference on causality, and given the right approach at data analysis it’s possible to “prove” that the density of crows on the telephone lines around your house is associated with your risk of halitosis or pancreatic cancer. Yes, somebody is paying for all these “scientific” association studies, which are published by the hundreds or maybe thousands every year.

But there is some more interesting experimental evidence suggesting that perhaps all those toxoplasma cysts in all those brains might be having a negative effect after all. Mice chronically infected with toxoplasma, and otherwise apparently well, loose their ability to smell cat urine—a pretty important survival skill if you’re a mouse. A June 16th article published in Plos Pathogens looks at previously unsuspected effects that “inert”toxoplasma cysts may be having in the brain. Nervous tissue is made up of neurons and critically important support cells called astrocytes, and communication between them is largely controlled by neuronal secretion of vacuoles containing a large number of proteins and other chemicals. These investigators found that chronically infected mouse neurons with toxoplasma cysts secrete fewer of these EV (extracellular vacuoles) and that their contents are highly different from uninfected neurons. This includes an important protein which controls the metabolism of glutamate (a critical neurotransmitter), and also that these EVs contain toxoplasma proteins and other compounds which ramp up the inflammatory cascade. We just might be on the verge of elucidating a plausible mechanistic explanation of prior observational data, and giving me a solid reason to regret all that beef tartare.

Toxoplasma gondii infection of neurons alters the production and content of extracellular vesicles directing astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain. Published: June 16, 2025

https://doi.org/10.1371/journal.ppat.1012733

The evolutionary question of where viruses came from is fascinating. Since they are totally dependent on the cells they infect to replicate their genetic material, it seems reasonable to presume that they must have evolved after unicellular organisms. There is a theory that viruses were more complex organisms which became simpler over time until they shed all the metabolic machinery of complex cells, and even the machinery to replicate their genetic material, instead hijacking an infected cell to do the job. Last month scientists reported in a bioRxiv pre-print the discovery of a minute parasite living inside the cells of a marine dinoflagellate (single celled organism). It was revealed by its tiny circular DNA containing only 189 genes, almost all of which appear to be related to reproducing its genome, and lacking any of the usual enzymes needed for cellular metabolism. Dubbed Sukunaarchaeum by the discoverers, the organism’s genetic sequences are typical of primitive unicellular life forms called archaeons—a lineage of living organisms distinct from bacteria and eukaryotic cells (that’s cells like ours, cactuses and fruit flies, which have the DNA contained in a nucleus separate from the rest of the cell). It just might be a living fossil showing us a previously more complex organism on an evolutionary trajectory toward becoming a virus.

A cellular entity retaining only its replicative core: Hidden archaeal lineage with an ultra reduced genome retaining only its replicative core. https://doi.org/10.1101/2025.05.02.651781

Over the last couple of years I have reported several times on Dengue, likely the most common serious viral disease transmitted by mosquitos, and the increasing yearly epidemics around the world. There is great variability among people with regard to how severe this infection can be; it was determined some time ago that genetics play a major role, and that African ancestry conveyed relative protection compared to a European genetic profile. (Are we allowed to talk about a “health disparity” here?). Another factor of course is the presence of antibodies from a prior dengue infection which can inadvertently cause a subsequent infection to be worse, the phenomenon of Antibody Dependent Enhancement (ADE). The first line of defense when an infected mosquito bites you is of course what happens in your dermis. Our skin is a large organ of protection and immunity with resident immune cells as well as other transiting immune cells which move from the vascular system into the dermis. There is an interesting study this month in PNAS from the dermatology and public health departments at Pitt School of Medicine. Using donated human skin they looked at genetic markers of single nucleotide variations and the response of the skin cells to infection with Dengue virus. They were looking at individuals with no prior evidence of Dengue, and found that the skin cells of individuals of European ancestry had markedly greater inflammatory responses to the virus than people of African ancestry. With increased inflammation there is increased infiltration of the skin by macrophages, which are cells responding to attack the virus; however with Dengue the macrophages become infected and may assist in faster dissemination of the virus around the body. People living in Africa where Dengue was endemic for millenniums selected for the trait of lower inflammatory response from the innate immune system in the skin, and that leads to less “friendly fire” attack on the rest of the body.

Genetic ancestry shapes dengue virus infection in human skin explants

http://dx.doi.org/10.1073/pnas.2502793122

That’s it for the science this go round. I will remark that a great deal of what’s wrong in our country currently is a lack of clear and present thinking. New York City appears to be on the verge of electing a young Communist, Islamist celebrating, racist, anti-semite. Don’t take my word for it, look at what he has said in person and broadcast on social media. Reasonable people may disagree on what a resolution to the conflict in Israel, Gaza and the West Bank should look like, but celebrating Hamas through its fund raising group, as Mandami has done, is despicable. Now I won’t deny that, anti-zionist, Jew-hatred has become all the rage recently among young “progressive”, university indoctrinated urbanites—but the Communism stuff shows a complete lack of activity above the brainstem. We have a pretty good track record in the twentieth century to understand that Communism is a guaranteed failure over and over, and leaves in its wake a gigantic body count—only tenured professors of Nonsense at our elite universities, divorced from any reality of having to occasionally be right to keep their jobs, could still be spouting this dreck. Yes, and the feeble minded young acolytes they turn loose on society, like Mandami. As far as the anti-semitism—well that’s a defect of the mind and sole that isn’t amenable to fixing by logical argument, that apparently is always bubbling beneath the surface in some individuals, but has been green lighted as a current cause celebre by the same university environments. Many people are blaming the Democrat party for choosing to run a flawed candidate like Cuomo, and as flawed an individual as he may be, its a simple exercise in clear and present thinking to see who would do less damage and perhaps some good to New York.

Go ahead pound that like button as if it’s your favorite politician to despise. I do not ever sell that information to the FBI, your boss, the DNC, RNC, your scoutmaster or religious leader. Comments are welcome about anything other than the outcome of the Diddy trial.