Anavex Life Sciences Corp (AVXL)

[makemydaze]

One line from your quote - "The two-fold higher increase of S1Rs was shown in the injured compared to the uninjured nerve by Western blotting." has had me spending too much time this morning wondering why and how did the number of SR-1's increase in the affected area.

That led me to read some articles on Schwann cells which may in part explain in part how Anavex 2-73 could possibly help with remyelination(through Schwann cell support-just my conjecture) and also gives some thought to the action of Anavex 1066 for pain -

"Our results complement Bangaru et al.'s finding that S1R expression is decreased in the cytoplasm of rat dorsal root ganglion (DRG) neurons and satellite ganglion cells of axotomized nerves. Due to the observed decrease in S1R expression in the DRG, the investigators conjectured that elevated S1R expression in neuropathic pain was not an explanation for pain relief after S1R blockade. In contradistinction, our results found increased S1Rs in the peripheral nerve at the site of nerve injury, some of which was realized in Schwann cells of the neuroma. It is therefore possible that, like glial cells in the central nervous system, S1R-enriched Schwann cells in the periphery play an important modulatory role in nociception. The increase of S1Rs in Schwann cells may also help explain the analgesic effect of S1R antagonists on neuropathic pain. Indeed, the persistence of Schwann cells in a chronic constrictive injury has been associated with the onset and persistence of neuropathic pain in this model. This agrees with our results from ultrasound-guided treatment of the neuroma; the ability to reduce pain by treating the site of injury with an S1R blocker (i.e., [19F]FTC-146) demonstrates the involvement of S1Rs within the sciatic nerve in the generation of neuropathic pain.

The increase in Schwann cell numbers seen in our experiments is not unexpected at approximately 4 weeks after nerve injury. Within a couple of days after the transection of rat sciatic nerves or nerve roots, Schwann cells pause their myelin producing function, upregulate genes associated with the repair process and begin proliferating. Initially, they remove degenerated extracellular debris, but approximately one week after the injury they recruit macrophages to continue this task. Finally, the Schwann cells seek to align themselves into bands of Bungner, to support regrowth of the injured axons. The peak rate of Schwann cell proliferation is reached within a week, but the increased cell numbers are sustained for several weeks in preparation for nerve regeneration."

http://www.thno.org/v07p2794.htm

and

"Recently, S1R has gained considerable attention as putative target of novel compounds possessing neuroregulatory properties. It has been shown by immunostaining that S1Rs are present in the cytoplasm of Schwann cells and in nodes of Ranvier but not within the myelin sheath or axons.
Moreover, S1R has been shown to co-localize with S100 protein-positive Schwann cells in the rat sciatic nerve and in cultured rat Schwann cells, thus indicating that S1R may regulate a major or constitutive function in Schwann cells."

https://www.researchgate.net/publication/316565685_The_Differentiation_of_Skin_Mesenchymal_Stem_Cells_Towards_a_Schwann_Cell_Phenotype_Impact_of_Sigma-1_Receptor_Activation

and finally

"Normally, Schwann cells do three things to encourage axon regrowth after injury. First, they clear the area of myelin, the insulating coating on axons that is thought to inhibit regeneration after injury. Second, they form tracts—similar to roadways—along which axons can regrow. Third, they secrete growth factors that stimulate regeneration.
“That entire process was not happening as efficiently in the old mice,” says Painter.
Though many dots need to be connected, the findings open a new avenue for promoting nerve regeneration—at least for peripheral nerves. Perhaps young Schwann cells could be transplanted into older patients. Or perhaps chemical factors could be introduced to kick-start Schwann cell function."

https://vector.childrenshospital.org/2014/08/can-old-peripheral-nerves-learn-new-tricks-only-the-schwann-cells-know-for-sure/