White/Grey Matter as a Neuronal Phenotype

Affordable whole genome sequencing is nearing ever closer and with it an urgency to develop more robust and quantitative diagnostic tools that might aid in objectively classifying neurological disorders. Biochemical & structural phenotypes that can be  readily and cheaply tested for is a worthy, though frustratingly elusive, pursuit across a wide spectrum of disorders. One such phenotype that appears with increasing frequency in much of the related literature is that of neuronal white & grey matter.

Some neurons have relatively few dendritic branches while others are highly branched in order to receive a great deal of information. Human axons can range from micrometres to almost five feet in length for a single cell. Photo by Bob Jacobs

First, let’s take a quick look at the basics. The fundamental building block of the central nervous system (CNS), the neuronal cell, is specialised to transmit information at up to 200 mph throughout the body via electrical and chemical messengers. However unlike other body cells, neurons stop reproducing shortly after birth (except neurons from the hippocampus) and often have to travel long distances from where they are created to where they will ultimately settle in the brain. While neurons do not reproduce, interneurons do create new connections between neurons within the same region of the brain or spinal cord throughout life.

A typical neuron possesses a cell body (often called the soma) dendrites, and an axon. The axon is a long extension of a nerve cell, and carries messaging information away from the cell body while dendrites often spread out over a considerable area and bring information in to the cell body via synapses at their tips. Another note worthy of mention is the myelin that coats and insulates the axon (except for periodic breaks somewhat exotically called ‘nodes of Ranvier’) which increases transmission speed along the axon.

So where does White & Grey Matter come in?

Generally, the CNS is considered to have two types of tissue, white and grey matter. As a computer analogy think of the grey matter as central servers and the white matter as the network cables connecting the servers together.

Grey matter is in reality pinkish-grey in living brains and is located in the centre of the spinal cord and the thin outer layer of the cerebral hemispheres, commonly known as the cortex. Grey matter consists of the cell bodies, dendrites and axon terminals (the end of the axon that connects to the dendrites and cell bodies of  other neurons), so it is where all synapses are and is primarily associated with processing and cognition. Grey matter is also distributed at the cerebellar cortex, as well as in the depths of the cerebrum, cerebellar, brainstem and spinal grey matter.

White matter of the human brain

A small fraction of white-matter fibers colour-coded according to their destination

Compare this to white matter which is made of axons connecting different parts of grey matter to each other and forms the bulk of the deep parts of the brain in addition to the superficial surrounding parts to the grey matter found in the spinal cord. Remember that white matter mostly contains myelinated axon tracts – which gives the matter its white colour when preserved in formaldehyde – in addition to the neuron support cells, glial cells. White matter is generally considered to be involved in how the brain learns and dysfunctions, modulating the distribution of action potentials, acting as a relay and coordinating communication between different brain regions [2].

White & Grey matter as a phenotype

Although too numerous in example to cite here, the composition and dimension of white and grey matter has been increasingly seen as symptomatic of several neurodegenerative and developmental conditions. For example  it has been shown in previous studies [3] that motor learning correlates with changes to white matter density while the volume and integrity of white matter has also been shown to correlate positively with reading ability [4]. White matter damage results in certain variants of Alzheimer’s disease in addition to other conditions such as  MS where the myelin shield around the axons is effected. Length of myelinated axon varies with both sex and age  and total length declines approximately 10% each decade due to the loss of thinner fibres – for example mutations in the genes encoding the subunits of eukaryotic initiation factor 2B have been involved in Vanishing White Matter (VWM), a disease characterized by slowly progressive ataxia and spasticity [5] Recent studies in developmental dyslexia show white matter alterations are in effect altering networks responsible for serving vital auditory-phonological as well as visual-orthographic functions [6].

Ultimately, studies increasingly demonstrate that different brain phenotypes support different behavioural phenotypes [7] with white and grey matter (in addition to cortical thickness) measurements being included in sample measurements.

A histogram of neurodegenerative-related research papers citing white/grey matter in the title (1990-2011). Click to enlarge.

References

As usual, there’s a wealth of information out there which I’ve reviewed, condensed and presented here. For a more detailed analysis see some of the references below.

[1]http://psychology.about.com/od/biopsychology/f/neuron01.htm [2]http://bit.ly/Nfyatu [3]http://www.nature.com/neuro/journal/v12/n11/abs/nn.2412.html [4] http://www.ncbi.nlm.nih.gov/pubmed/22683091  [5] http://www.ncbi.nlm.nih.gov/pubmed/20975056 [6]http://bit.ly/NDLPcc [7] http://bit.ly/Mc7llU

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