Aging and its 11 hippocampal genes

Aging is being quite extensively studied these days and here is another advance in the field. Pardo et al. (2017) looked at what happens in the hippocampus of 2-months old (young) and 28-months old (old) female rats. Hippocampus is a seahorse shaped structure no more than 7 cm in length and 4 g in weight situated at the level of your temples, deep in the brain, and absolutely necessary for memory.

First the researchers tested the rats in a classical maze test (Barnes maze) designed to assess their spatial memory performance. Not surprisingly, the old performed worse than the young.

Then, they dissected the hippocampi and looked at neurogenesis and they saw that the young rats had more newborn neurons than the old. Also, the old rats had more reactive microglia, a sign of inflammation. Microglia are small cells in the brain that are not neurons but serve very important functions.

After that, the researchers looked at the hippocampal transcriptome, meaning they looked at what proteins are being expressed there (I know, transcription is not translation, but the general assumption of transcriptome studies is that the amount of protein X corresponds to the amount of the RNA X). They found 210 genes that were differentially expressed in the old, 81 were upregulated and 129 were downregulated. Most of these genes are to be found in human too, 170 to be exact.

But after looking at male versus female data, at human and mouse aging data, the authors came up with 11 genes that are de-regulated (7 up- and 4 down-) in the aging hippocampus, regardless of species or gender. These genes are involved in the immune response to inflammation. More detailed, immune system activates microglia, which stays activated and this “prolonged microglial activation leads to the release of pro-inflammatory cytokines that exacerbate neuroinflammation, contributing to neuronal loss and impairment of cognitive function” (p. 17). Moreover, these 11 genes have been associated with neurodegenerative diseases and brain cancers.

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These are the 11 genes: C3 (up), Cd74  (up), Cd4 (up), Gpr183 (up), Clec7a (up), Gpr34 (down), Gapt (down), Itgam (down), Itgb2 (up), Tyrobp (up), Pld4 (down).”Up” and “down” indicate the direction of deregulation: upregulation or downregulation.

I wish the above sentence was as explicitly stated in the paper as I wrote it so I don’t have to comb through their supplemental Excel files to figure it out. Other than that, good paper, good work. Gets us closer to unraveling and maybe undoing some of the burdens of aging, because, as the actress Bette Davis said, “growing old isn’t for the sissies”.

Reference: Pardo J, Abba MC, Lacunza E, Francelle L, Morel GR, Outeiro TF, Goya RG. (13 Jan 2017, Epub ahead of print). Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats. Hippocampus, doi: 10.1002/hipo.22703. ARTICLE

By Neuronicus, 25 January 2017

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Your blood is better than my blood

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Siamese tomatoes. Taken from here.

Parabiosis is a surgical procedure that lets two animals to share the same blood; it’s a case of reverse conjoined twins restricted to the circulatory system.

The procedure is over 150 years old and is a useful technique in physiology, though rarely used, probably due to the perceived cruelty towards the animals, although today is performed under anesthesia and aseptic condition. It delivered good data; for example, it was a parabiosis experiment with rodents that showed is not the sugar in the blood that causes cavities but the sugar in the mouth. Similarly, parabiosis has been proven useful in cancer, diabetes, and ageing research.

Scudellari (2015) wrote a News piece for Nature describing some advancements in the ageing field using the parabiosis technique. Namely, by joining the circulatory systems of a young and an old mouse, researchers have observed that the old mouse is faster, smarter, with rejuvenated muscles and glossier fur. Now the race is to find out what in the blood does it. Researchers caution that the young blood is not effectively reversing ageing, but may have factors circulating in it that promote tissue repair. Already a muscle-rejuvenating protein has been identified.

I am not going through the original papers themselves as I usually do (they are provided as links in the Reference paper). Instead, I am featuring the news piece by Scudellari because in addition of looking at parabiosis and ageing result, it also provides a nice historical account of the use of parabiosis. Enjoy!

Reference: Scudellari, M. (22 Jan 2015). Ageing research: Blood to blood. Nature, 517: 426-429. Article | FREE Fulltext PDF

By Neuronicus, 4 January 2015