LONGECITY

In 2012 it was reported that

 

findings suggest that ACh may contribute to the maintenance of an immature proliferating progenitor pool and impair the progression toward mature stage.

That lead to a 2013 animal study using benztropine (a selective M1 muscarinic acetylcholine receptor antagonist.) showing that it "induces OPC maturation".

Now in 2015, a new study using CDP choline it was shown that

 

CDP-choline effectively enhanced myelin regeneration and reversed motor coordination deficits. The increased remyelination arose from an increase in the numbers of proliferating oligodendrocyte precursor cells and oligodendrocytes.

But CDP choline increases acetylcholine so what gives?

Sources:

http://www.ncbi.nlm....pubmed/21913336

http://www.scripps.e...009lairson.html

http://www.ncbi.nlm....pubmed/25524711

One possible explanation stems from the fact that CDP-choline =! acetylcholine. The 2015 paper published in Brain suggests that the mechanism by which CDP-choline promotes proliferation of oligodendrocytes is via the second messenger diacyl glycerol (DAG), which is essential for protein kinase C (PKC) activation. In this study, all PKC inhibitors blocked the effect of CDP-choline on oligodendrocyte proliferation.

Often in biology it seems that one signaling molecule will elicit opposite effects as a kind of negative feedback loop. E.g., thyroid hormone release increases the metabolism of many cells of the body, but also suppresses thyroid-stimulating hormone (TSH), reducing thyroid release. Analogously, one could imagine that CDP-choline would promote oligodendrocyte proliferation, while at the same time acetylcholinergic activation of the muscarinic receptors would arrest proliferation. (This is all highly speculative, but at least it's a start). 

 

 

Effects of CDP-choline on OPC proliferation in vitro. CDP-choline increased the proliferation rate of OPCs in cell culture experiments as measured by BrdU incorporation (A, n = 4). In B exemplary stained proliferating OPC (green BrdU, red A2B5) are shown after incubation with CDP-choline compared to controls (nuclei were counterstained with DAPI). Inhibition of the enzyme phospholipase C (PLC), which is required for the activation of the enzyme diacyglyceride (DAG), reversed the additional proliferative effects induced by CDP-choline (C, n = 4). Phosphatidylcholine (end product in the CDP-choline pathway) did not induce any effects on OPC proliferation (D, n = 5). DAG is essential for the activation of protein kinase C (PKC) and three different inhibitors (Bis = bisindolylmaleimide IV: Calph = calphostin C: Chelery = chelerythrine chloride) were tested with CDP-choline in OPC cultures. All PKC inhibitors completely reversed the additional proliferative effects of CDP-choline (E, n = 5). Bars represent mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001. The schematic overview (F) shows that CDP-choline is converted directly with DAG to phosphatidylcholine and CMP (cytidine-mono-phosphate) in a reaction catalyzed by CPT (1,2-diacylglycerol cholinephosphotransferase). DAG is a product of the hydrolysis of PIP2 (phosphatidylinositol 4,5-bisphosphate) by the membrane-bound enzyme PLC (phospholipase C) and is an essential physiological activator of protein kinase C. Our results show that the inhibition of PLC and thereby DAG reverses the CDP-choline effect on proliferation. DAG is essential for protein kinase C activation and it can be suggested that CDP-choline exerts its effects on proliferation via DAG and thus via protein kinase C activation, as we could show that inhibition of PKC activity reversed the CDP-choline effects on proliferation and phosphatidylcholine had no effects on proliferation. PIP2 = phosphatidylinositol 4,5-bisphosphate.

Basically CDP increases olygodendrocytes through a different mechanism than benztropine. I experienced two different results using these. While on CDP choline my neuropathy had stabilized but was not improving. After stopping it and starting low dose benztropine symptoms became overactive (no functional differences yet) and raising the dose only caused a spread to parts of my spine that are more or less intact. Now i wonder what myelination feels like and if i should get back on CDP.

 

Mice either received CDP-choline (500 mg/kg) or saline (control group) by daily oral gavage

And at what dose ?

Basically CDP increases olygodendrocytes through a different mechanism than benztropine. I experienced two different results using these. While on CDP choline my neuropathy had stabilized but was not improving. After stopping it and starting low dose benztropine symptoms became overactive (no functional differences yet) and raising the dose only caused a spread to parts of my spine that are more or less intact. Now i wonder what myelination feels like and if i should get back on CDP.

 

 

Mice either received CDP-choline (500 mg/kg) or saline (control group) by daily oral gavage

 

And at what dose ?

May I ask what the cause of your peripheral neuropathy is? Have you looked into B-vitamin products like metanex? 

Peripheral only? i wish. I dont think i heard of metanx until now. Although i used to take P5P and 5-MTHF. Only methyl b12 now.