The Professionals: Fanfiction: Wondering Why?
20 Mar 2026 02:07 pmAuthor:
Rating: Teen and up
Summary: Spoilers for the episode Spy Probe. Doyle wonders where he went wrong.
Pairing: Bodie/Doyle
Word Count: 200
( Wondering Why? )

1. What was the reason you began a Dreamwidth or LiveJournal account (or both)?
I started LiveJournal in 2002 when a new friend (soon girlfriend) heard me saying that I wanted to write more and suggested LiveJournal. "What's LiveJournal?" I said, and she gave me an invite code, and here I am.
I moved to DW in 2011, I can't remember which exact thing made me do it but it was after Strikethrough, before things got very Russian but I think they were getting pretty Russian.
2. How many DW or LJ communities do you subscribe to?
Five.
3. Do you have a favorite community or one you check out often to see what's new?
I mean, they're all on my reading page. Most are pretty quiet; one I made for covid-cautious people and don't use much myself any more either (its name is a pun based on "herd immunity," that's how old it is...). The best are
thisfinecrew, for U.S. political actions people can taken (often online or relatively low-spoons) and
thissterlingcrew, the British version of the same thing. Very useful communities to have In These Times.
4. How did you pick your user name?
This one was picked by D and another friend (I now cannot remember who) independently when I was looking for a new one.
5. If you could change your user name, would you?
It's clearly from a very specific time in my life, when I was using the name Cosmo and studying linguistics.
As for changing it, I mean, I could. I have. My LJ went through a couple of names too. I almost never re-use user names either; I just use whatever sounds like a good idea at the time. I can barely remember what it was before, and would probably prefer that one now. I did make a concerted effort to get away from puns, things based on my real-life first name, or both; no wonder this is what my friends suggested for me, this is my Brand.
While I'm here, another point I've been meaning to make under this tag for a bit but haven't gotten around to: having been writing about my life for half of it now, I find myself wishing there was a way for tags to become, like, dormant or something. There are lots of tags that I want to keep having but am not going to add new entries to, so I wish I didn't always have to look at them in the list or when I'm choosing tags.

If only Voldemort had thought of that.*
* EDIT: Yeah, okay, so he did. I totally forgot about that! Ooops.

psst if you sign up for the $5/month tier on my patreon you can see the (very nsfw) thirst pic
How are you doing?
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We need a theme.
- It has to be a socially conscious theme.
One that reflects the students' growing awareness of...
...and involvement in the world around them.
Here’s the other cognition/aging/Alzheimer’s paper that caught my eye. In a similar way to the work I highlighted yesterday on proteins released by the liver affecting the blood-brain barrier and overall brain function, this one is finding another external signal, from from an unexpected direction.
The authors studied the intestinal microbiomes of mice as they aged, and found that species that produce medium-chain fatty acids become more and more prevalent. Then a complex series of events start taking place: these metabolites are ligands for the human GPR84 protein and can drive inflammation in myeloid cells through that activation. This in turn weakens the neural traffic through the vagal system, and this loss of “interoceptive” signaling to the brain leads to a decline in hippocampal function. Impaired memory, in other words.
Now that’s one that I wouldn’t have seen coming, but as the paper shows in its references, there are a number of other reports pointing in this microbiome/memory direction. Now overall, the signal/noise of microbiome work is not as high as it should be, but papers like this new one are an important step in shoring up such hypotheses, trying to bridge some of the “by some mechanism that we haven’t figured out yet” gaps. It’s not that new and interesting ideas have to eliminate all of those leaps, but if you have to invoke that sort of thing too many times you’re asking for trouble. Here’s how you avoid that (hint: it involves an awful lot of work).
One experiment done here was to house very young (two-month old) mice with old (18-month-old) ones, which led to exchange of microbiome species between the two cohorts and an equilibrium that looked quite a bit more like the old ones. This didn’t seem to have any real effects on physical health and energy levels (or even things like exploratory behavior), but the short-term and long-term memory task performance of the young mice declined. To control for social effects, the team tried things like direct faecal microbiome transplants from the old mice into the young ones, and this recapitulated the memory effects all by itself. Meanwhile, co-housing gnotobiotic (germ-free) mice of both age groups did not affect the memories of the younger ones. Similarly, treating regular groups of young and old mice with two weeks of antibiotics also restored memory task performance in both cohorts.
And yes, the aged germ-free mice also performed much better on memory tests than the ones with typical microbiomes, so all of these results point in the same direction. There appears to be a gut microbial factor that impairs memory in older mice. Looking at the bacterial species that were present across different ages, Parabacteroides goldsteinii looked like the top candidate. (That one has already been the subject of a great deal of microbiome work in humans, as that link will show) Colonizing either germ-free or post-antibiotic mice with this species alone brought on the memory trouble, but this effect could not be demonstrated with other species that increased with age, nor with some that showed no real change as the mice aged.
Looking at the brains of the impaired mice, it appeared that neuronal function was disrupted in the hippocampus and in several areas known to be involved with sensory processing. A weird and interesting result was that many of the neurons involved in the vagus nerve’s gut-to-brain connections express the TRPV1 vanilloid receptor. Chemogenetic silencing of this receptor gave memory behavior similar to the aged mice, while activation of it seemed to restore function in the elderly cohort. That extended even to such low-tech methods as giving the mice capsaicin as a TRPV1 agonist (!) Other gut-responsive signals such as CCK or GLP-1 showed improvements in the presence of added agonists, although their underlying levels were not changed with aging and/or P. goldsteinii infection.
Further experiments showed that (as mentioned above) medium-chain fatty acids produced by those bacteria seem to be the actual signal driving these effects. Oral administration of things like decanoic acid and 3-hydroxyoctanoic acid were enough to affect cognition by themselves, and demonstrated effects along the whole causal chain the above work had laid out (vagus nerve activation and the sensory and hippocampal brain regions). These are known to be ligands for GPR84, and the team showed that mice with inactivating mutations in that receptor were immune to the effects of added medium-chain acids and showed delayed onset of memory trouble in general as compared to wild-type mice. The receptor is largely found in myeloid cells (macrophages, monocytes, and neutrophils) and ablating these also restored memory function (demonstrated through a set of bone-marrow experiments).
This looks to me like a very solid paper where the authors have tried to shore up every step of their hypothesis. Inflammation-driven defects in interoceptive signaling truly does look like a cause of memory decline in mice: but does it work that way in humans? You can bet that work is going on as we speak to find that out, but this pathway fits in very well with the overall idea that inappropriate inflammation is a driver of age-related brain dysfunction. But I have to say, we weren’t looking for it first in the gut rather than directly in the brain! There’s clearly a lot of work to be done here, and direct pharmacological intervention in these interoceptive pathways could really be beneficial. Starting with more hot sauce, given those capsaicin results? Try it today!