MULTIPLE SCLEROSIS

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Demyelination is the major underlying factor responsible for the symptoms of multiple sclerosis (MS). Demyelination is the destructive removal of myelin, an insulating and protective fatty protein which sheaths nerve cells (neurons). More specifically, the myelin is wrapped around the long extensions of neurons called axons. During MS relapses, patches of white matter in the central nervous system that normally contain tracts of myelinated neurons become inflamed and lose their myelin. These patches of demyelination are known as lesions.

The cause and precise mechanism of demyelination is not clearly understood but there is good evidence that the body's own immune system is at least partially responsible. Acquired immune system cells called T-cells are known to be present at the site of lesions. Other immune system cells called macrophages (and possibly mast cells as well) also contribute to the damage.

Myelin is produced by special "glial cells" in the central nervous system called oligodendrocytes. Oligodendrocytes and axons have a many to many relationship - that is one oligodendrocyte produces myelin for several axons and one axon has several oligodendrocytes producing its myelin. In MS, it is not just the myelin that is destroyed but also these oligodendrocytes and occasionally even the axons themselves.

Axons use an electrochemical mechanism to transmit nerve impulses - the action potential. This requires sodium and potassium ions to pass through a semi-permeable membrane around the nerve. It is believed that the myelin not only insulates and encases this electrochemical process but also actively assists it. When axons become demyelinated, they transmit the nerve impulses 10 times slower than normal myelinated ones.

During periods of MS remission, the oligodendrocytes repair the damaged axons in a process called remyelination. However, very often the oligodendrocytes are also destroyed which delays or prevents remyelination from happening. Additionally, another kind of glial cell, called astrocytes, cause scar tissue to form in place of the myelin. Scar tissue does not perform the same function as the myelin. As the disease reaches its more advanced phases, the axons themselves are often destroyed as well.

Demyelination links:
Demyelination
Multiple Sclerosis: Etiology
Demyelination, Neurodegeneration & Metabolic Disorders CNS
Demyelination: The Role of Reactive Oxygen and Nitrogen Species
Biochemistry of Demyelination
Cell Death During Autoimmune Demyelination
Gender Differences in Autoimmune Demyelination

Myelin is a collection of lipid fats and proteins that sheaths the long extensions of nerve cells (neurons) called axons. Myelin considerably increases the speed that nerve signals (impulses) move down the axons. For example, a thin myelinated axon transmits impulses at anything from 5 to 30 metres per second whereas an unmyelinated one transmits them at 0.5 to 2 meters per second. It does this both by insulating and containing the nerves.

See this diagram of a neuron which shows how the myelin wraps the axon:

A nerve impulses is a wave of depolarising current called an action potential that travels along the entire neuron by allowing charged ions of sodium and potassium to flood through channels in the semi-permeable membrane around the nerve cell. At rest (resting potential) the neuron and the surrounding space act as a "capacitor" storing current which is released during the action potential.

Myelin increases the speed of the transmission by containing the current (as positively charged ions) in a small space surrounding the axon. This means that the sodium and potassium ions that contribute to the resting potential do not have far to move when the action potential occurs. Myelin also prevents current from being lost as sodium ions drift away from the neuron.

The myelin sheath is broken at intervals called the nodes of Ranvier which are rich in sodium channels. This makes the nerve impulses move in a stepwise fashion called "salutatory conduction".

Myelin is composed of about 80% lipid fats and about 20% proteins. Some of the proteins that make up myelin are Myelin Basic Protein (MBP), Myelin Oligodendrocyte Protein (MOG) and Proteolipid Protein (PLP).

Myelin occurs in both the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) but the cells that produce the myelin differ. In the PNS, cells called Schwann cells produce and maintain the myelin whereas, in the CNS, glial cells called oligodendrocytes produce and maintain the myelin.

In Multiple Sclerosis the myelin is destructively removed from around the axon which slows down nerve impulses in a process known as demyelination. In MS, axons are demyelinated in inflammatory patches called lesions. As the disease progresses oligodendrocytes and ultimately the axons themselves are destroyed. Their is very compelling evidence that the destruction is caused by the body's own immune system i.e. that multiple sclerosis is an autoimmune disease.

Moreover it is likely that immune response is mediated by a division of the specific immune system called cellular immunity. Cellular immunity is driven by a type of white blood cell (leukocyte) called a T-cell. These T-cells recognise particular sub-sections of proteins called antigens. It seems likely from animal models of multiple sclerosis (experimental autoimmune encephalomyelitis) that initial relapsing-remitting phases of the disease centre on one antigen component, perhaps of myelin basic protein, but that, as the disease progresses, antigens from other proteins become involved.

Myelin
Myelin
Anatomy of the nervous system
myelin sheath
Disorders & Research Of Myelin
Myelin & Schwann Cell Components

The peripheral nervous system (PNS) refers those nerves (neurons) that are not part of the brain or spinal cord. Nerves inside the brain and spinal cord are part of the central nervous system (CNS). PNS nerves have their cell bodies (ganglia) inside the CNS but their length outside it. The PNS consists of neurons with both myelinated and unmyelinated axons. All the cranial nerves (the 12 pairs of nerves leaving the base of the braincase) are part of the peripheral nervous system although the second cranial nerve (the optic nerve) can be considered as part of the brain.

There are two kinds of nerve in the Peripheral Nervous System:

1. Motor or efferent nerves. These are the nerves that connect to muscles in the limbs, torso, face and internal organs. They carry nerve signals from the CNS and make body parts move. The cell bodies of the motor nerves connect to CNS in the shaft of grey matter in the spine called the anterior horn. They terminate at a neuromuscular junction known as the motor plate or motor end plate. Neurotransmitters released by the motor nerves into the motor plate cause the muscle to contract.
    
2. Sensory or afferent nerves. These are nerves that connect to sensory organs and sensors in the skin, muscle and internal organs. They take relay nerve signals to the CNS. They convey heat, touch, position (proprioceptive), balance, sound and other information from the limbs and sense and internal organs. Sensory nerves terminate in the CNS at the root ganglion.

The peripheral nervous system is divided into two parts:

1. The sensory-somatic nervous system (SNS).
    

The SNS is performs all our interactions with the physical world such as control of our limbs and receiving of conscious information from our senses. It consists of the 12 pairs of cranial nerves and the 31 pairs of spinal nerves.

2. The autonomic nervous system (ANS).
    

The ANS consists of both motor and sensory nerves which run both to and from the central nervous system and fulfills "automatic" functions that we are seldom aware of such as heart activity and the release of hormones. The autonomic nervous system is further divided into the sympathetic nervous system and the parasympathetic nervous system.

Peripheral Nervous System links:
The Peripheral Level
The Nervous System (Peripheral Nervous System)
The Peripheral Nervous System
The Motor End Plate
Nervous System Lecture Notes