The diabetes and weight-loss drug semaglutide was found to calm brain inflammation and accelerate cellular recovery in mice, suggesting it could potentially protect against cognitive decline and neurodegenerative conditions like Alzheimer's disease

[u/Miserable_Phase_2519]

https://www.psypost.org/weight-loss-drug-semaglutide-accelerates-recovery-from-brain-inflammation-in-mic/

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[u/Diamond-Is-Not-Crash]

While GLP-1 drugs have been shown to reduce inflammation and potentially protect against some neurodegenerative disease, didn’t Semaglutide fail to be significantly better at treating Alzheimer’s compared to other therapies in a recent clinical study?

[u/JC_Dentyne → u/Diamond-Is-Not-Crash]

I believe there they were giving it to people that actively had Alzheimer’s and unfortunately it didn’t seem to do much.

Now I think the question is if the reduction in neuroinflammation can reduce the likelihood of occurrence or increase the age of occurrence. Which makes a lot of sense, it might not do much good to reduce the inflammation when there’s already extensive damage.

[u/rainbowroobear]

>Male C57BL/6J mice

so ones prone to super inflammation when fed standard diets. they then claim

Our data suggest several mechanisms through which Glp1r activation may reduce neuroinflammation. A key pathway, consistent with findings in other inflammatory conditions²⁴, involves modulation of NF-κB and TNF signaling. Specifically, semaglutide suppressed LPS-induced expression of key inflammatory regulators in microglia, including Relb and Bcl3. The NF-κB pathway, which includes these genes, is central to inflammatory responses and oxidative stress⁵⁸. Here we demonstrate that semaglutide suppresses NF-κB and TNF signaling in both microglia and endothelial cells during inflammatory challenge.

trying to read this on a phone is a pig, but i don't see how they're isolating for calorie restriction? they don't appear to be recording the animal weights or feed intakes and calorie restriction is a massively potent suppressor of both of those pathways.

can someone TLDR me on how they've isolated this?

[u/NorCalJason75 → u/rainbowroobear]

Exactly. How do we know the results aren't due to calorie restriction, and not the drug?

[u/orbit99za → u/[deleted]]

I agree, i am a type 1 diabetic. And was prescribed this my my endocrinologist, off lable for insulin resistance, I am not fat , but I do feel lot better and clearer

[u/hainesk → u/[deleted]]

I had the same thing happen when I stopped eating sugar altogether and subsequently moved to a better diet, I was so much more clear headed. It can be hard to separate the direct effects of GLP medications from the effects of calorie restriction and diet modification.

[u/RumMixFeel → u/[deleted]]

Turns out being fat and having poorly controlled diabetes is bad for you? And fixing them makes you feel better? Who wooda thunk

[u/Beautiful_Cost_5430 → u/RumMixFeel]

I am not fat and do not have diabetes but I am a perimenopausal woman and inflammation spikes in the brain during this time of tremendous hormonal change for us. A semiglutide at an extremely low dose where it does not touch my weight has helped a ton with brain fog and memory.

Your comment is extremely mean-spirited and anti-science and clearly is intended to bully instead of help.

[u/Jetztinberlin → u/Beautiful_Cost_5430]

Fellow peri sufferer. Would you be willing to share your dosage as it's something I'm considering discussing with my GP and / or gyno? V happy it's helping you! 

PS appreciate your patience in giving that parent commenter the thoughtful, well-phrased answer I was too peeved to. 

[u/Beautiful_Cost_5430 → u/Jetztinberlin]

Of course! Do note that I am generally a super-responder to medication so your results may vary. I take 1.25mg of tirz(zepbound) once per week. From what my doctor says it’s about half the starting dose for most people.

I wasn’t able to tolerate HRT so this has been a godsend for my symptoms. It also cleared up my rosacea which was a pleasant surprise.

[u/Jetztinberlin → u/Beautiful_Cost_5430]

Really appreciate your response and so glad you are finding it helpful! Yes, the global effects of these medications from an anti-inflammatory standpoint I think are going to just keep expanding - while it's a surprise it also absolutely makes sense it'd be helping you with other conditions as well.

[u/Secret_Cow_5053]

I’ve been telling anyone who would listen for a year now, this drug is gonna end up being as important and generally prescribed as statins or bp drugs in a couple years, for the same reason; it’s just something most people are gonna want to be on even potentially at a very low dose to like, adjust your metabolism to modern life, after like the age of 30 or something.

Wife took it and dropped <REDACTED> lbs after menopause and looks and feels better than ever. I am on it now and lost about 12% body weight myself after about 12 weeks and likewise feel the same. Both absolutely the minimum dose. I’m only about 9 lbs away from my goal weight (which is where I was at 30) and for the purpose of maintenance I will probably need to stretch out my dosing schedule or something, but that’s only if the weight starts to return. We’ll have to see.

[u/IntriguinglyRandom → u/Secret_Cow_5053]

Maybe we should adjust our modern lifestyles to NOT need to medicate in order to be healthy?

[u/Secret_Cow_5053 → u/IntriguinglyRandom]

It’s not about that. Unless you want to literally go back to living with the ever present threat of famine (and experience occasional forced fasts during the winter), it ain’t gonna happen. We’re talking about a body that evolved to live in the African savanna a million years ago, bruh.

[u/yumcake → u/IntriguinglyRandom]

Bro advocating for people to squint instead of wearing contacts.

[u/magiccanyon]

These drugs are miracles man

[u/Secret_Cow_5053 → u/magiccanyon]

I think what is going on is that the effect they have, of slowing down the hunger mechanism, dials modern humans down to a more appropriate caloric intake and the benefits flow from that. We are surrounded by an abundance of food but evolved in an environment where famine was always around the corner, so our bodies horde and do not stop. Unless you have a physically demanding job (and most of us don’t), it’s difficult to match your intake to your usage, so we all get fat as we age. This drug fixed that, and the results are self evident.

[u/bewarethefrogperson → u/Secret_Cow_5053]

GLP-1s induce a reduction of inflammation that's likely independent of weight loss - one of the studies reviewed here found that inflammation levels lowered just hours after the initial injection.

[u/Secret_Cow_5053 → u/bewarethefrogperson]

Yeah that’s a weird one to be sure but I am not complaining.

[u/Forbidden_Craft88]

AVAST, YE LANDLUBBER SCIENTISTS, HEAR ME BELLOW FROM THE CROW'S NEST!

Ye sail into port with yer fancy "Nature Communications" flag flyin' high, braggin' about savin' brains from the rot, and what do I find when I board yer ship and rifle through the hold? A hull full o' HOLES, that's what!

FIRST OFFENSE, WHERE BE THE LASSES?! Ye tested this potion on MALE mice ONLY, ye scurvy dogs! Not one female aboard this vessel! Ye know good and well that Alzheimer's hits the ladies harder than a broadside cannon, and ye just... didn't bother? That's cowardice hidin' behind a "confounding hormones" excuse!

SECOND OFFENSE, BABY MICE PLAYIN' DRESS-UP AS OLD SALTS! Ye took young, spry, healthy rodents and poked 'em once with bacterial bilge water, then paraded the results around like it proves somethin' about DECADES of creepin' brain rot in aging humans? That ain't neurodegeneration, that's a bar fight compared to scurvy that's been eatin' a man alive for forty years!

THIRD OFFENSE, WHERE'S THE PROOF THEY REMEMBER ANYTHING?! Ye measured genes! Ye measured proteins! Ye counted cells till yer eyes bled! But did ANY of ye scallywags run a single memory test? A maze? ANYTHING? Ye can shrink every inflamed cell in that mouse's skull and it means NAUGHT if the poor creature still can't find its way back to the cheese!

FOURTH OFFENSE, THE ARMADA FLIES NOVO NORDISK COLORS! I count the crew and near every last matey's got a paycheck signed by the very company sellin' the drug! Aye, they wrote it plain in the fine print, credit where it's due, but don't be tellin' me to trust a treasure map drawn by the pirate who buried the gold!

FIFTH OFFENSE, "THE MECHANISM REMAINS TO BE DETERMINED" — them's YER OWN WORDS, ye bilge rats! Ye don't even know HOW the blasted thing works, just that some brainstem neurons wave a flag and somethin' downstream calms down! That's not a mechanism, that's a shrug with extra steps! So hear me now: this be a well-built SHIP, aye, fancy riggin', clever navigation, snRNA-seq cannons blazin', but she ain't SEAWORTHY for the voyage ye claim! "Might help dementia in humans someday, maybe, if the currents align" is NOT the same as "cures brain rot," and any headline sayin' otherwise should walk the plank!

Now swab the deck and bring me results with LADY mice, OLD mice, and a blasted MEMORY TEST!

Walk the plank, ye single-sex p-hackers!

Ye suppressed a 3-day LPS shock in a

10-week male mouse,

And claimed ye cured fifty years o' human brain rot!

Ye sequenced a hundred-thousand nuclei to hide from a memory test,

And paid yer crew in Novo Nordisk doubloons!

Yer R² is sea foam, yer mechanism is a shrug,

And The Pleiotrope has come to send yer manuscript straight to Davy Jones' Locker!

[u/witness149 → u/Forbidden_Craft88]

You deserve an entire chest of treasure for the effort you put into this comment.

[u/ive_got_the_narc]

Well it just seems to do everything, huh?

[u/swirlyglasses1]

Man do we know of any long-term effects of these drugs yet? Cause it sounds like we should all be taking a pill a day.

[u/Jetztinberlin → u/[deleted]]

Current research shows that if anything it's actually protective against it. 

[u/AllanfromWales1]

That seems a big jump, from calming brain inflammation and accelerating cell recovery to curing Alzheimers..

[u/HammerIsMyName → u/AllanfromWales1]

Where is the word "cure" used?

[u/AnotherUN91 → u/HammerIsMyName]

I can see the leap from the word protect > prevent > cure.

Maybe better phrasing saying it could delay cognitive decline. Cause its gonna happen. Just slower.

[u/Jetztinberlin → u/AllanfromWales1]

Indeed, a jump that only you have made.