1: Oligodendrocytic Na +-K +-Cl - co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain.
Science of the Month - November 2021
Yoshihiko Yamazaki*, Yoshifumi Abe*, Satoshi Fujii, Kenji F Tanaka. (*equal contribution)
Myelin-forming oligodendrocytes (OLs) depolarize when neural activity increases, further accelerating axonal conduction velocity (GLIA 2014). As a result, synaptic transmission efficiency increases (J Neurosci 2019). In this study, we determined that these facilitatory effects are high in the brains of young individuals and low in adult brains, and that the responsible molecule is NKCC1 expressed in OLs. Our next challenge was to address the question, "Can memory and learning be improved simply by increasing the expression of NKCC1 in OLs, which has decreased in adulthood?" The answer was yes. This paper demonstrates that rejuvenating OL function is a viable option for rejuvenating brain function. Incidentally, the diuretic furosemide is an inhibitor of NKCC1, but since furosemide does not cross the blood-brain barrier, you can rest assured that it does not cause aging of OL function.
(Kenji Tanaka, 76th Graduating Class, and Yoshifumi Abe, equivalent to the 89th Graduating Class, Division of Brain Science, Institute for Advanced Medical Research)
2: Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians.
Nature.
2021 Jul 29. doi: 10.1038/s41586-021-03832-5.
Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, Kearney SM, Suda W, Takeshita K, Sasaki T, Okamoto S, Skelly AN, Okamura Y, Vlamakis H, Li YX, Tanoue T, Takei H, Nittono H, Narushima S, Irie J, Itoh H, Moriya K, Sugiura Y, Suematsu M, Moritoki N, Shibata S, Littman DR, Fischbach MA, Uwamino Y, Inoue T, Honda A, Hattori M, Murai T, Xavier RJ, Hirose N, Honda K.
In this study, with the cooperation of Dr. Yasumichi Arai and Dr. Nobuyoshi Hirose of the Center for Supercentenarian Medical Research, we collected fecal samples from domestic supercentenarians (average age 107) and analyzed their gut microbiota and metabolites. As a result, we found that compared to younger (20–50 years old) and elderly (80–90 years old) individuals, the intestinal tracts of supercentenarians showed an increase in bacterial gene clusters related to bile acid metabolism. Analysis of bile acids in the feces revealed a significant increase in a secondary bile acid called isoallolithocholic acid, which is metabolized by gut bacteria. Using a proprietary screening system, we identified bacterial strains from the feces of supercentenarians that produce isoallolithocholic acid and further elucidated the bacterial pathway for its production. In addition, we discovered that isoallolithocholic acid suppresses the growth of gram-positive pathogenic bacteria at extremely low concentrations. From these findings, it was hypothesized that the abundance of isoallolithocholic acid in the intestines of supercentenarians may contribute to maintaining a healthy gut environment.
(Kenya Honda, equivalent to the 73rd Graduating Class, Department of Microbiology and Immunology)
Other Published Papers
1: Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy.
Nature Communications.
Takamatsu K, Tanaka N, Hakozaki K, Takahashi R, Teranishi Y, Murakami T, Kufukihara R, Niwa N, Mikami S, Shinojima T, Sasaki T, Sato Y, Kume H, Ogawa S, Kakimi K, Kamatani T, Miya F, Tsunoda T, Aimono E, Nishihara H, Sawada K, Imamura T, Mizuno R, Oya M.
2: Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of H-1-magnetic resonance spectroscopy studies.
Molecular Psychiatry.
Nakahara T, Tsugawa S, Noda Y, Ueno F, Honda S, Kinjo M, Segawa H, Hondo N, Mori Y, Watanabe H, Nakahara K, Yoshida K, Wada M, Tarumi R, Iwata Y, Plitman E, Moriguchi S, de La Fuente-Sandoval C, Uchida H, Mimura M, Graff-Guerrero A, Nakajima S.