Saturday, March 09, 2013

Nociceptive musings3

"Hi there - me again, C fibre. I thought you might like to know a bit more about what turns neurons on. Here is an excerpt from The Nerve Growth Factor: A New Tool for Manipulating Neurons:"
"The human nervous system is a vast network of several billion neurons, or nerve cells, endowed with the remarkable ability to receive, store and transmit information. In order to communicate with one another and with non-neuronal cells the neurons rely on the long extensions called axons, which are somewhat analogous to electrically conducting wires. Unlike wires, however, the axons are fluid-filled cylindrical structures that not only transmit electrical signals but also ferry nutrients and other essential substances to and from the cell body. Many basic questions remain to be answered about the mechanisms governing the formation of this intricate cellular network. How do the nerve cells differentiate into thousands of different types? How do their axons establish specific connections (synapses) with other neurons and non-neuronal cells? And what is the nature of the chemical messages neurons send and receive once the synaptic connections are made?" - Neurobiologist Rita Levi-Montalcini, and Pietro Calissano, first published in Scientific American June 1979, republished Jan 3, 2013 after Rita Levi-Montalcini's death on Dec 30 2012.

"How indeed? Rita Levi-Montalcini was great. She discovered and wrote about nerve growth factor, which is what makes me ... well, I can't say 'big&strong', because I'm one of the thinnest long neurons that exist - so I'll just say, healthy."

"The peripheral nervous system of vertebrate animals includes three kinds of nerve cells: sensory neurons, which transmit impulses from sensory receptor structures to the brain; motor neurons, which innervate the striated, or skeletal, muscles, and autonomic neurons, which regulate the functional activity of the circulatory system, the organs, the glands and the smooth muscles (such as those of the intestine). Autonomic neurons are of two kinds: sympathetic and parasympathetic. The sensory neurons and some of the sympathetic neurons are situated in chains of ganglia flanking the length of the spinal cord. Because these neurons are uniquely accessible to experimental manipulation much of the research on the development of the nervous system at the cellular level has focused on how the nerve fibers projecting from the sensory and sympathetic ganglia make connections with their corresponding target organs."

" Well, as it turns out, this stuff is irresistible. To neurons. Ones like me, for example. Not only C afferents like me, but those sympathetic efferents too. I can only assume that is how I ended up in this situation, leading a boring life but for the occasional flare-up at my terminal end, nothing else much to report, staying alive... staying alive..

"Here's how I guess I was born.

"Once upon a time there was this single cell that divided itself up like crazy, turned into layers. One layer turned into a whole bunch of stuff that gave off signals of something Delicious. Another layer was turning into cells that could smell all this deliciousness, and struggled to follow after it. I was one of the cells in that latter layer. I escaped! I migrated a little way but then realized I was trapped at one end - I couldn't move anymore! But I could sure grow... and I did, until I could stay in constant contact with the Most Delicious Of All That Is Delicious, and relax. This seemed to take years, but finally the organism I am part of stopped increasing in size. Things have been pretty quiet ever since, on the growth side, at least..

"But back to the Levi-Montalcini story, which reads like a thriller: Nerve growth factor was first found in mouse tumors and snake venom. How about that! Later it was found in ordinary saliva. It wasn't the so much the stuff that mattered very much, it was the quality and type and folding arrangement of protein in the stuff that made it either Perfectly Delicious, or didn't. And do you know what else? If a neuron like me who smelled the Delicious and took off to find a place to plug into it, didn't find a good place to plug in, it died. So many fell in those first days, weeks, months..  But I digress.

"Here's how it works, according to this paper:"

"Once the elongating fibers have estab­lished the appropriate synaptic contacts with the target cells, the continued sur­vival of the innervating cells in the gan­glion appears to depend on the availa­bility of NGF. Studies conducted by Hendry at the Australian National Uni­versity and by K. Stockel and H. Thoe­nen at the Basel Institute for Immunol­ogy have demonstrated that NGF is taken up at the terminal nerve endings of the sympathetic fibers and transport­ed back to the neuronal cell body along the axon. This retrograde axonal trans­port of NGF is absolutely essential for the survival of the innervating neurons. When it is experimentally prevented (either by severing the projecting axons, by treating them with the drug vinblastine, which blocks axonal transport, or by ad­ministering 6-hydroxydopamine, which destroys the nerve endings), the inner­vating sympathetic neurons in the gan­glion die off.  The lethal effects of block­ing the axonal transport of NGF can be completely overcome, however, by sup­plying the cell bodies with externally administered NGF. In this case the exter­nal NGF makes up for the NGF that would normally be transported back in­side the axon to the cell body from the innervated cells."

"Absolutely essential. Our life blood you could say.
" I build receptors to capture the proteins:"

"Work in several laboratories has shown that the retrograde axonal transport of NGF follows its interac­tion with specific receptor sites on the nerve terminals of the newly established fibers. Receptors are proteins that are usually located on the external surface of the cell membrane; they provide spe­cific recognition sites for messenger substances such as hormones, neuro­transmitters and growth factors."

"Other kinds of cells can feed off that NGF too, you know, like cancer cells. And they can also make it.
"Anyway, to wrap up - that paper was written 34 years ago. Levi-Monalcini died just a few months ago, over a hundred years old. Her neurons all worked very well, it would seem, right up to the end.

"Since then research has uncovered all kinds and flavours of the Delicious. As long as there is enough of the Delicious, we can keep going for a very, very long time, we neurons can."

Nociceptive musings

Nociceptive musings 2

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Nociceptive musings 6

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