Relax - Unravelling genes

During development there is obviously a need for our nervous system to be quite plastic. Over the first few years after birth this potential for plasticity gradually diminishes until around 5 years old when our nervous system beds down and largely loses the ability to repair itself efficiently.

One of the ways the body does this is by selectively switching off those genes that allow neurons to grow axons and form new synapses. Since it cannot delete the gene it must inactivate it some other way. The DNA in our chromosomes is tightly packed and the degree of packing influences how efficiently genes are expressed.

This is the fundamental basis of something called epigenetics. Packing is modified depending on the level of chemical modification of the DNA and something called histone around which the DNA is packed. Drugs can interfere with the levels of chemical modification which in turn can lead to a relaxation of the packing structure and greater expression. This could be useful for switching back on genes that once allowed plasticity in the developing nervous system. A Petit [Presentation #450.08] examined the effects of the anticancer drug Trichostatin A, or TSA (a histone deacetylation inhibitor) on neurons in vitro and found it to increase the amount of sprouting and axonal outgrowth in tissue culture. Given once a day for two weeks starting 1hour after experimental injury, systemic injections of TSA gave rise to enhanced functional recovery, increased axonal growth in and around the lesion, enhanced tissue sparing and modification of the immune response to the injury. The data presented was from studies carried out on female rats - apparently, male rats don't respond nearly so well! I'm assured they are looking into the reasons for that.