BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A

Your doctor should be jumping for joy on this because it seems to address one of the causes of the neuronal cascade of death. But I bet not a single neurologist in the world will create a stroke protocol out of this to help stroke survivors. I welcome any and all neurologists to explain why you aren't doing anything about this. Saying it is not completely proven by research is not a valid excuse because YOU should be doing the research to prove it then.
http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2900798-6?

David Lau

,

C. Peter Bengtson

,

Bettina Buchthal

,

Hilmar Bading

Open Access

DOI: http://dx.doi.org/10.1016/j.celrep.2015.07.038

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Open access funded by the Author(s)

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Highlights

• •BDNF-induced neuroprotection requires synaptic NMDA receptors and nuclear calcium
• •BDNF-nuclear calcium signaling induces transcription of inhba/activin A
• •Activin A reduces toxic extrasynaptic NMDA receptor signaling, shielding mitochondria
• •Activin A protects against excitotoxic cell death in cultured neurons and in vivo

Summary

The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating synaptic NMDA-receptor/nuclear-calcium-driven adaptogenomics, leading to increased expression of inhibin β-A (inhba). Inhibin β-A (its homodimer is known as activin A) in turn reduces neurotoxic extrasynaptic NMDA-receptor-mediated calcium influx, thereby shielding neurons against mitochondrial dysfunction, a major cause of excitotoxicity. Thus, BDNF induces acquired neuroprotection by enhancing synaptic activity and lowering extrasynaptic NMDA receptor death signaling through a nuclear calcium-inhibin β-A pathway. This process, which confers protection against ischemic brain damage in a mouse stroke model, may be compromised in Huntington’s disease, Alzheimer’s disease, or aging-related neurodegenerative conditions that are associated with reduced BDNF levels and/or enhanced extrasynaptic NMDA receptor signaling.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).