CCL11 found in aged but not young blood inhibits adult neurogenesis

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Portion of Fig. 1 from Villeda et al. (2011, doi: 10.1038/nature10357) describing the parabiosis procedure. Basically, under complete anesthesia, the peritoneal membranes and the skins of the two mice were sutured together. The young mice were 3–4 months (yellow) and old mice were 18–20 months old (grey).

My last post was about parabiosis and its sparse revival as a technique in physiology experiments. Parabiosis is the surgical procedure that joins two living animals allowing them to share their circulatory systems. Here is an interesting paper that used the method to tackle blood’s contribution to neurogenesis.

Adult neurogenesis, that is the birth of new neurons in the adult brain, declines with age. This neurogenesis has been observed in some, but not all brain regions, called neurogenic niches.

Because these niches occur in blood-rich areas of the brain, Villeda et al. (2011) wondered if, in addition with the traditional factors required for neurogenesis like enrichment or running, blood factors may also have something to do with neurogenesis. The authors made a young and an old mouse to share their blood via parabiosis (see pic.).

Five weeks after the parabiosis procedure, the young mouse had decreased neurogenesis and the old mouse had increased neurogenesis compared to age-matched controls. To make sure their results are due to something in the blood, they injected plasma from an old mouse into a young mouse and that also resulted in reduced neurogenesis. Moreover, the reduced neurogenesis was correlated with impaired learning as shown by electrophysiological recordings from the hippocampus and from behavioral fear conditioning.

So what in the blood does it? The authors looked at 66 proteins found in the blood (I don’t know the blood make-up, so I can’t tell if 66 is a lot or not ) and noticed that 6 of these had increased levels in the blood of ageing mice whether linked by parabiosis or not. Out of these six, the authors focus on CCL11 (unclear to me why that one, my bet is that they tried the others too but didn’t have enough data). CCLL11 is a small signaling protein involved in allergies. So the authors injected it into young mice and Lo and Behold! there was decreased neurogenesis in their hippocampus. Maybe the vampires were onto something, whadda ya know? Just kidding… don’t go around sucking young people’s blood!

This paper covers a lot of work and, correspondingly, has no less than 23 authors and almost 20 Mb of supplemental documents! The story it tells is very interesting and as complete as it gets, covering many aspects of the problems investigated and many techniques to address those problems. Good read.

Reference: Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. (31 Aug 2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 477(7362):90-94. doi: 10.1038/nature10357. Article | FREE Fulltext PDF

By Neuronicus, 6 January 2016


Prions in urine

toilet urine

This is one of the scariest papers I have read.

All prion diseases – like the mad cow disease, scrapie, Kuru or Creutzfeldt-Jacob (CJD) – are incurable and fatal. Up to recently, we thought the only way you can get it is by ingesting the meat of the affected animal. Or, as I reported a couple of months ago, by ingesting drugs derived from the pituitary glands of infected dead humans.

A paper published 4 years ago describes another unexpected way to contract this horrible deadly disease. Using electrophoresis, mass spectrometry and liquid chromatography selected reaction monitoring, Van Dorsselaer et al. (2011) found prion proteins in a class of infertility drugs, the injectable urine-derived gonadotropins. These drugs are given to hundreds of thousands of women in North America for infertility treatment. They are developed from the urine of donor women, who are screened for all sorts of diseases, but the CJD has a long incubation period (decades) and thus it may be un-detectable using non-invasive methods.

Now, this in itself is not so worrisome as additional screening of the final medicine can be done and eliminate the batches with prions. What scared the living you-know-what out of me is the thought that the infected humans pee in the toilet and then that goes to the water treatment plants and then comes to your faucet. My question is: can the purification done at the water treatment plant eliminate the prions? I really, really do not wish to be alarming and panicky, especially in a world where every other news you read/hear seems to be something scary, so I invite anybody with knowledge about water treatment to comment and let us all know that is impossible, or at least highly unlikely, to get prions from the drinkable water. I don’t know how, maybe some step in the water treatment kills proteins as a matter of course or something.

Reference:  Van Dorsselaer A, Carapito C, Delalande F, Schaeffer-Reiss C, Thierse D, Diemer H, McNair DS, Krewski D, & Cashman NR. (23 Mar 2011). Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach. PLoS One, 6(3):e17815. doi: 10.1371/journal.pone.0017815. Article | FREE FULLTEXT PDF

By Neuronicus, 18 November 2015