http://anelloclinic....fits-of-lithium This article says 10-20 mg per day of lithium orotate can regrow the neurons in your brain.
The rest of this post is about lithium preventing Alzheimer's disease.
But first, it helps to understand AMPK activation by its alpha, beta, and gamma subunits
AMPK has 12 different variants in different tissues, resulting from each subunit having several variations. AMPK gets activated when cells are underfed during starvation, fasting, or muscle exhaustion. One could write a book about all the things AMPK does to restore/maintain ATP to help us survive starvation. AMPK has 3 control subunits alpha, beta, and gamma which all must be enabled to activate AMPK. (1) The alpha subunit is usually activated globally by liver kinase B1 (LKB1) which is normally present but provides the liver with a master deactivation switch. However, in neurons, the alpha subunit is enabled instead by CAMKK2 when it senses a high Ca2+ level in the cell. (2) The beta subunit is deactivated by glycogen on a cell by cell basis. An ample supply of glycogen in a cell inhibits AMPK (eg in muscles). In neurons the beta subunit may be deactivated by some other excess energy substrate, but in the study below it appears to be normally activated. (3) The gamma subunit is activated by a low ATP/AMP ratio on a cell by cell basis ie this is the local "energy sensor". It gets turned on by low ATP in a cell. Take away - AMPK is activated in neurons when two things happen:(1) CAMKK2 at the alpha subunit senses high Ca2+, and (b) the gamma subunit senses low ATP/AMP ratio (assuming the gamma subunit works the same in neurons as everywhere else).
http://www.cell.com/...6273(13)00133-5 This article says the cause of old age onset Alzheimer's disease is phosphorylation of the tau protein in neurons by activated AMPK. The repeatedly phosphorylated tau proteins end up in tangles that kill the neuron.
Article Summary:
Neuron AMPK is activated when CAMKK2 at its alpha subunit senses a high Ca2+ level in the neuron. Ca2+ influx comes through a pore gated by the N-methyl-d-aspartate (NMDA) receptor and blocked by a Mg2+ ion. The pore gets opened when the NMDA's two subunits are activated and a blocking Mg2+ ion moves out of the pore after the neuron has been completely depolarized for a sufficiently long time. Ca2+ rushes in at the beginning of the repolarization cycle (before Mg2+ can plug it up again). Take away - Alzheimer's needs Ca2+ influx which needs both NMDA subunits to be activated, and the neuron to be completely depolarized. Complete depolarization requires multiple firings within a short period of time. NMDA subunits require a molecule made by adjacent support cells (several different molecules work) and a gradual accumulation of glutamate created when neurons fires. (Only a tiny bit of glutamate reaches the NMDA receptor at a time).
https://www.ncbi.nlm...icles/PMC19446/ "Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-d-aspartate receptor-mediated calcium influx"
The title says it all. Lithium inhibits Ca2+ influx through the NMDA. That prevents the CAMKK2 Ca2+ sensor from turning on the alpha subunit of AMPK. It follows that less AMPK activation -> less tau tangles -> less neuron death -> less Alzheimer's. However, the author is quick to say that lithium slows down Alzheimer's, but does not prevent it (?). It seems to me the gamma subunit of AMPK has to turn on too, and that shouldn't happen in neurons, if the brain is never allowed to starve. Maybe the gamma subunit in neurons gets activated a different way.
I'm going to up my lithium orotate to 5 mg/day for now, and continue my research.
Edited by RWhigham, 21 December 2016 - 04:42 AM.
