New study on exercise, ketones, and BDNF

[marthaNH]

https://elifesciences.org/content/5/e15092

Mouse study, but encouraging and achievable. There is also an article today in the New York Times about it, but the author seems to actually discourage anyone from trying to act on the information. I find their coverage to be very defeatist when it comes to weight, exercise, etc.

[Julie G]

LOL, yes exercise is incredibly dangerous. We'd best remain sedentary until this connection is proven in humans . FWIW, here's the article from the NYT. FWIW, the author's not particularly discouraging this time.

[circular]

Oooo, good study.

The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly [ie not exclusively?] promoter I, which is activity-dependent. [Emphasis added]

I'm a little confused by the phrase 'activity-dependent'. It seems like the paper is also suggesting that ketosis generally induces BDNF in the hippocampus. I'm looking for some solace. These exercise studies always require a level of intensity I can't (yet?) achieve because of other health issues, and I'm heteroz on the BDNF SNP, but I hope my ketogenic diet will stand in for some of the exercise intensity I miss out on.

For example:

In order to mimic the increases in DBHB in the brain observed after exercise, we injected mice with 2-deoxy-d-glucose (2-DG), a structural analog of glucose that inhibits glycolysis and increases the brain’s capacity to utilize ketone bodies as fuel. 2-DG is transported by glucose transporters into the cell where it binds to, but cannot be phosphorylated by hexokinase, resulting in the inhibition of the first step of glycolysis (Ralser et al., 2008). This inhibition leads to the activation of a compensatory mechanism resulting in the production of ketone bodies by the liver. By activating this alternative energy pathway, 2-DG treatment induces DBHB levels in the brain. Interestingly, we found that 2-DG injection, like exercise, also induces both DBHB levels and Bdnf expression in the hippocampus to a similar extent (Fig 6A and B).

[circular]

Interestingly, according to Promethease's summary, there are at least 3 BDNF SNPs that when heterozygous increase risk of AD among non-e4 carriers. I'm heteroz on all three, but have one e4, so I wonder if this is neutral for me or takes my e3 and raises the risk of that portion of my apoe gene.

[PMID 17293537OA-icon.png] Alzheimer's disease risk for non ApoE4 carriers is affected by the heterozygous form of rs6265, as well as the diplotypes of rs6265, rs11030104, and rs2049045. [Huang involved in this one]

The paper itself:

METHODS:
We examined 11 SNPs that spanned the gene on chromosome 11p14 in 220 Alzheimer's patients and 128 control spouses.
RESULTS:
Not all of the SNPs were informative, due to minor allele frequencies of <2%. Neither C270T nor two SNPs that reside proximal to exon V had significant association with the disease. However, we did find that the heterozygous form of the rs6265 SNP (Val66Met), as well as the diplotype of three SNPs (rs6265, rs11030104, rs2049045; H1-GTC/H2-ACG) all were highly significant in APOE 4 non-carriers (OR = 2.734; p = 0.0096).