NERVOUS SYSTEM BASICS

[Diane]

I am about to drive everyone (look out, proud...) mad here on this forum this summer, bringing forward information about glia. I just got Glial Neurobiology (Verkhratsky and Butt) and Neuroglia 2ndEd (Kettenmann and Ransom) in the mail. Whoohoo. Look out.

[Diane]

Bonanza!
I found an online version of a new book I bought, Glial Neurobiology. It just came out last year.

You have to download it in chunks, and it's not free, but it's great.

Preface

Contemporary understanding of brain organization and function follows the neuronal doctrine, which places the nerve cell and neuronal synaptic contacts at the very centre of the nervous system. This doctrine considers glia as passive supportive cells, which are not involved in the informational exchange, and therefore secondary elements of the nervous system.

In the last few decades, however, our perception of the functional organization of the brain has been revolutionized. New data forces us to reconsider the main postulate of the neuronal doctrine – that neurones and synapses are the only substrate of integration in the central nervous system. We now learn that astroglial cells, which are the most numerous cells in the brain, literally control the naissance, development, functional activity and death of neuronal circuits. Astroglial cells are in fact the stem elements from which neurones are born.

They also create the compartmentalization of the CNS and integrate neurones, synapses, and brain capillaries into inter-dependent functional units. Furthermore, astroglial cells form a functional syncytium, connected through gap junction bridges, which provides an elaborate intercellular communication route. This allows direct translocation of ions, metabolic factors and second messengers throughout the CNS, thereby providing a sophisticated means for information exchange. In a way the binary coded electrical communication within neuronal networks may be considered as highly specialized for rapid conveyance of information, whereas astroglial cells may represent the true substance for information processing, integration and storage.

Will this truly heretical theory which subordinates neurones to glia be victorious at the end? Forthcoming years hold the answer. When writing this book we have attempted to create a concise yet comprehensive account of glial cells and their role in physiology and pathology of the nervous system. We hope very much that this account may help the reader to discover a
fascinating world of brain ‘secondary’ cells, which in fact are essential elements of the nervous system, whose functions and importance are yet to be fully appreciated.

Alexei Verkhratsky (now at U. Manchester)
Arthur Butt

[Diane]

I haven't found out yet whether or not microglia eat their own dead, but they certainly eat all the other dead. Here is a paper about it.
What is so cool about this, in my mind anyway, is the reference to the ancient-ness of receptors of various kinds. It really does look like it's the receptors where all action is, that are the "immortal" parts, i.e., not changing much through time. I guess once a good one gets built, one that works to reduce a chemo-gradient, there is no point in changing it. "Nature abhors a gradient" (Into the Cool, Sagan/Schneider). Back to Seth Grant and System Proteomics, which is what finally got me going on glia in the first place.

[Diane]

I'm still checking out glia, in particular microglia, and their relationship to the nervous system, dorsal horn, pain facilitation. In looking up information about Linda Watkins I found this paper, Gateways to Pathological Pain at TheScientist.com.

Points to take home:
1.

With regard to what turns p38 on in the spinal cord, "the search is on," says Linda Watkins, professor of psychology at the University of Colorado, Boulder. Imagine the peripheral neuron firing with intensity, sending signals into the dorsal horn of the spinal cord. "Some are very unique neuron-to-glia signals, such as fractalkine," says Watkins. Fractalkine is a protein in the chemokine family that is expressed only on the outside surface of neurons. Shed from neurons sending distress signals, fractalkines bind to and activate nearby glial cells. "The only cells that express receptors for [fractalkine] are microglia," says Watkins.

OK, so the neurons send out distress calls, and like a nervous sweat, fractaline emerges on their surfaces, and microglia are drawn like sharks to blood.

2.

In addition to hypertrophy, there is hyperplasia. "Perhaps the most dramatic thing that [microglia] do is they divide," says Wolfgang "Jake" Streit, professor of neuroscience at University of Florida's Evelyn F. and William L. McKnight Brain Institute in Gainesville. "They divide like you wouldn't believe."

They are capable of nearly tripling their numbers in a short time.

[Diane]

I found a recent paper (see Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain)

It talks about those P2X receptors. Every time I see P2X I immediately associate it with microglia - for better or worse, microglia have definitely made themselves apparent to me as being unavoidable players in pain.

[Diane]

Here is another one, open access this time.
Monocyte chemoattractant protein-1 functions as a neuromodulator in the dorsal root ganglia neurons.

Abstract:
It has previously been observed that expression of chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 is upregulated by dorsal root ganglion (DRG) neurons in association with rodent models of neuropathic pain. MCP-1 increases the excitability of nociceptive neurons after a peripheral nerve injury, while disruption of MCP-1/CCR2 signaling blocks the development of neuropathic pain, suggesting MCP-1 signaling is responsible for heightened pain sensitivity. In order to define the mechanisms of MCP-1 signaling in DRG, we studied intracellular processing, release, and receptor-mediated signaling of MCP-1 in DRG neurons. We found that in a focal demyelination model of neuropathic pain both MCP-1 and CCR2 were upregulated by the same neurons including TRPV1 expressing nociceptors. MCP-1 expressed by DRG neurons was packaged into large dense-core vesicles (LDCVs) whose release could be induced from the soma by depolarization in a Ca2+-dependent manner. Activation of CCR2 by MCP-1 could sensitize nociceptors via transactivation of transient receptor potential (TRP) channels. Our results suggest that MCP-1 and CCR2, upregulated by sensory neurons following peripheral nerve injury, might participate in neural signal processing which contributes to sustained excitability of primary afferent neurons.

Karen has probably already seen this. In fact Karen has probably already linked it here somewhere..

One other thing I've learned, for better or worse, monocyte = immune system = microglia = little pests.

[amacs]

indebted

Hi Diane

superb material, thank you for posting these links

ANdy

[Diane]

ANdy, you are welcome.
I appreciate that you found and are reading them.

[rkathryn]

Diane, I'm a little late getting these copied and am really looking forward to reading them. Thank you so much!

[Diane]

My pleasure.

[Diane]

Check out "Translational Pain Research: From Mouse to Man" - chapters are available to read online.

As one would guess from the title, the word "pain" is substituted for "nociception" all the way through. However, it's a great collection of info.

[Curious]

Thank you Diane for making these. A lot of knowledge you have gathered.:thumbs_up

I was reading this paper and I would like to get some clarification on this part which I have quoted.

Axonal transport consists of various components. Fast axonal transport (as much as 410 millimeters per day) involves various enzymes, transmitter substance vesicles, and glycoproteins, and slow transport (as much as thirty millimeters per day) involves primarily cytoskeletal elements such as subunits of microtubules and neurofilaments.

In the paper reads that for example slow transport (as much as 30 mm per day) involves cytoskeletal elements. Does that mean the nerve could acquire length 30 mm per day or just that the elements are being transported with that speed to wherever they are needed through the axon?

In the 7th part: Anatomy of a Neuron is written about neurofibrils:

they play a vital role in intracellular transport of vesicles and organelles which move along their surface through cell body and along axon
- they turn over constantly

Did intracellular transport mean moving inside only one particular cell?

Are the elements being transported in epi or perineurium or in some smaller or larger scale?(only moving inside one cell)?

[Diane]

I was reading this paper and I would like to get some clarification on this part which I have quoted.

Axonal transport consists of various components. Fast axonal transport (as much as 410 millimeters per day) involves various enzymes, transmitter substance vesicles, and glycoproteins, and slow transport (as much as thirty millimeters per day) involves primarily cytoskeletal elements such as subunits of microtubules and neurofilaments.

In the paper reads that for example slow transport (as much as 30 mm per day) involves cytoskeletal elements. Does that mean the nerve could acquire length 30 mm per day or just that the elements are being transported with that speed to wherever they are needed through the axon?

The latter, the elements are being transported with that speed to wherever they are needed through the axon. Literal growth in length is a lot slower.

In the 7th part: Anatomy of a Neuron is written about neurofibrils:

they play a vital role in intracellular transport of vesicles and organelles which move along their surface through cell body and along axon
- they turn over constantly

Did intracellular transport mean moving inside only one particular cell?

Are the elements being transported in epi or perineurium or in some smaller or larger scale?(only moving inside one cell)?

Inside one cell.
"Intra" means "inside", and "cellular" means "cell". :angel:

[AnnaGates]

Thank you for posting all of this helpful material and the great links. It is greatly appreciated!

[Diane]

You are most welcome Anna.