Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 3 • June/July 2012


Increasing Neurogenesis in Mice With (-)-Epigallocatechin-3-gallate (EGCG)

While in a creative intoxicated state, you may also like to increase your brain’s supplies of newly created neurons via neurogenesis. The hippocampus of the brain, critically important in learning and memory, is one of the two known brain areas that contain resident neuronal progenitor cells, which can generate new neurons throughout life.

In the new study,1 researchers provided male C57BL/6J mice EGCG by oral administration (25 mg/kg)* and BrdU by intraperitoneal injection for incorporation into the newly formed neurons, thus allowing for their detection. Neuronal development was detected by Ki67 as an endogenous marker of proliferation and DCX as a marker for neuroblasts.


* This is roughly equivalent to a dose of 100 to 200 mg per day of EGCG for a human as scaled by metabolism.


The researchers observed that, “oral administration of EGCG for 4 weeks enhanced the number of proliferating cells in the SZDG [subgranular zone of dentate gyrus, where progenitor cells reside] based on Ki67 and BrdU immunohistochemistry. EGCG induces rescue of the brain volume alteration in accelerated senescence mice (SAMP 10) and DYRK1a gene-deleted mice. DYRK1a, an essential gene for normal postembryonic neurogenesis, is involved in the neuronal differentiation of hippocampal progenitor cells in rats. … [t]hese findings suggest that the treatment of EGCG promotes the cell proliferation.” In addition, “[a]dult neurogenesis is stimulated by brain-derived neurotrophic factor (BDNF). It has been reported that EGCG diet enhances BDNF mRNA levels in the hippocampus of the human brain.” The authors note that EGCG can easily pass through the blood-brain barrier and reach the brain parenchyma, unlike most other blood-borne substances.

Finally, the scientists observed “an increase in numbers of DCX+ cells in the EGCG-treated group compared to those in the vehicle-treated group.”1

Newly Created Neurons Perform Differently From “Mature” Neurons: Youthful Vigor

Something that has been recently discovered is that the newly minted neurons function somewhat differently than older neurons, acting as a sort of vigorous childhood version of the old neurons.2 It has been reported that the new cells learn more easily and have greater overall levels of activity than older ones, with a threshold to induce long-term potentiation (a process required for learning and memory) signal transmission that is reduced in comparison with the older, mature neurons.2 It has been proposed that for a short period of time after their formation, the young neurons are more sensitive to excitatory input as compared to older ones.2

Marin-Burgin et al, researchers in the field of neurogenesis, speculate that, “the mix of young and old cells imparts a particular functionality to the dentate gyrus. Young neurons are good integrators and tuned to a broad variety of inputs, whereas old cells display high input specificity and hence are better separators.”2,3 The CELL study3 authors sum their findings: “[o]ur data suggest that as adult-born GCs [granule cells] age, their function switches from pattern separation to rapid pattern completion.”

References

  1. Yoo et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res 24:1065-70 (2010).
  2. Kempermann, “Perspectives: Youth culture in the adult brain,” Science 335:1175-6 (2012).
  3. Nakashiba et al, “Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion,” Cell 149:188-201 (2012).

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