Question I'm trying to answer is: how do HDACi antagonise NgR?

If that doesn't make sense, HDACi = HDAC inhibitors, drugs that unwind/loosen DNA from it's chromatin spool allowing the encoded proteins to be transcribed (I've got another page detailing all of this), NgR is the Nogo-66 receptor which is on a neuron's neurite-surface-membrane, and to antagonise means to disable.

As the brain structure grows, myelin / oligodendrocyte (M/OD) wraps around
neurites, and chemical messages get sent from this wrapper (presumably the tightest fold that actually borders the neurite being wrapped) to the neurite telling it to not grow any more.

"Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro."

from Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury

So if we can either …

  1. prevent M/OD from sending out these chemical messengers, or …
  2. prevent the (NgR) receptor from acting on them,

…we will lift the brake on axon growth.

I'm writing M/OD because the brain tends to use oligodendrocyte, whereas the spinal-cord uses Myelin. Central nervous system (CNS) = Brain + spinal-cord = neurons wrapped in myelin + neurons wrapped in oligodendrocyte. I guess that's why the neuron's NgR responds to messengers sent by each.

I think it might be possible to do the first one by degrading Myelin.

I'm not sure if this is related to PNN degradation through ChABC.

From Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor

Chondroitin sulfate proteoglycans (CSPGs) are astrocyte-and neuron-derived axon-outgrowth inhibitors that have also been implicated in OD plasticity. Infusion of chondroitinase ABC into spinal cord–injured animals cleaves glycosaminoglycan chains and promotes a degree of regeneration and functional recovery (29) comparable to that of Nogo/NgR antagonism (8, 11).

No, this is wrong. This is a completely separate mechanism. Here we have PV cells producing GABA. Gradually Otx2 gets produced by visual stimulus and somehow fed back into these PV cells. Specifically it gets caught in PNNs (peri neuronal nets) that cobweb onto PV cells. And this persuades the PV cell to produce more GABA.

"Exactly how PNN-like structures regulate brain function remains unknown." <— Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex 2012!!! :(

Same paper…

"We propose that PNNs persistently maintain a non-permissive state for plasticity beyond the CP by perpetually sustaining Otx2 transfer above a critical threshold within PV-cells, which themselves need to be plastic for a CP to arise"

So it makes sense. This is a sensory experience feedback loop. Sensory experience generates Otx2, which gets caught in PNNs wrapped around PV cells. These PV cells respond to this Otx2 by producing GABA which closes CP.

But wait! I thought that PV cells maturing and producing GABA OPENED CP.

Now I am confused.

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