The immune system, the brain and light therapy – surprising or unsurprising new findings?
In a new study in the PloS Biology Journal, Ania Majewska, Assistant Professor of the Department of Neurobiology and Anatomy and researchers from the University of Rochester Medical Center have discovered that immune cells called microglia can cause changes in the dendritic spine structures of neurons or nerve cells in normal subjects – healthy mice in this study. This is a confirmatory study of the interaction between the immune system and the dendritic spines of neurons even in health. The changes in immune system activity and dendritic spine density was related to excessive light/darkness exposure.
In order to understand the importance of this study the following information may be helpful:
The Structure Of Nerve Cells (Neurons)
There are several parts of neurons or nerve cells. These are
1. The synapses.
2. The dendrites.
3. The cell body.
4. The axon.
Click here for a diagram of a neuron or nerve cell. There are about 100 billion nerve cells in the brain.
It is recommended that you watch this short video before reading this article as it may improve the understanding of the article.
The tree model of brain disease – video
Dendrites are fibres which receive information from other neurons.The dendrites are tree-shaped. Dendron means “tree” in Ancient Greek. Dendrites have protruberances on their surface called dendritic spines rather like leaves on a tree. Dendritic spines have receptors or synapses on their surface. Synapse means “connection” in Ancient Greek.
Synapses receive chemicals or neurotransmitters from other nerve cells. The axon is a single fibre which transmits information to other neurons. Axon means “to go or to travel” in Ancient Greek.
In a recent study Professor John Armstrong found that changes in spine or leaf density and length precede changes in synaptic strength and number. This confirms the importance of the spines or leaves in being required for synapse development. Generally speaking the more dendritic spines there are on a dendrite the more electrical activity and firing of electrical signals or “firing rates” there are. However many questions remain unanswered.
In most neurological and psychiatric diseases there are changes in the shape of neurons and in particular the dendritic spines. The dendritic spines or leaves are generally reduced in number and density. This may be compared to the reduction of the leaves on a tree which occurs from summer into winter.
Trying To Understand The Immune System.
The immune system is both simple and complex. One of the simplest approaches is as follows:
1. The immune system is exposed to a substance which may be
a) An immunogen e.g. food, bacteria, chemicals, drugs.
b) An auto-immunogen e.g. cancer cells, mutant enzymes and their products.
2. The immune system`s macrophages, dendritic cells or microglia devour the substance (phagocytosis) and become antigen presenting cells (APC).
3. Some of the substance is revealed to the rest of the immune system on the surface of the APC on MHC II complexes.
4. White cells called helper T-cells connect to the complexes.
5. White cells called regulatory T-cells (TREGS) either permit or prohibit the next stage of the immunogenic response.
6. If permitted the helper T-cells activate killer T-cells and antibodies to destroy the substance.
7. Substances called cytokines such as TNF are released which cause tissue damage.
It seems as though TREGS control the effects of microglial activity.
The Immune System In The Brain
The dendritic spine abnormalities described above are associated with immune system activation.
It seems that for most other organs in the body it is beginning to be accepted that the immune system is regulated by the white cells called regulatory T-cells or TREGS. (For more information check out “Mechanism of Disease: Evolving Role of Regulatory T Cell in Atherosclerosis: TREGs in Human Autoimmune Disorders on medscape.com)
The immune system in the brain is abnormal in most neurological and psychiatric disorders. This suggests that the changes in dendritic spines are inflammatory in nature. Inflammation of the dendritic spines is described as dendritis or dendropathy.
Which immune cells control the immune system in the brain?
There is current debate regarding which immune cells are the most important in the control of the immune system in the brain. The microglia in the brain will recognise abnormal antigens or auto-antigens and devour them. Parts of the antigen are then exposed to the white cells called T helper cells which if activated lead to the immunogenic response and inflammation of the dendrites or dendritis.
TREGS seem to control the immunogenic response. Therefore it is likely, as in most other organs, TREGS control microglial activity. However TREG abnormalities are not assessed in this new study of the effects of light on the immune systems interaction with dendritic spines.
What is the effect of light on TREGS?
This study confirmed that there is a significant increase in TREGS following ultra-violet light treatment. The more TREGS there are the less the immunogenic response and less inflammation.
What were the effects of light and dark on the brain in the study?
The study exposed healthy mice to prolonged periods of light and darkness and alternating lightness and darkness.
Microglia became more active, devouring more (phagocytic) in darkness and as anticipated in the tree model of brain disease resulted in reduction in dendritic spine density (dendritis) due to the increased immunogenic response.
Light exposure reversed these abnormalities i.e. microglia became less active and dendritic spine density increased. Light reduced the immunogenic response.
How do the beneficial effects of light on the immunogenic response correlate with clinical features of neurological and psychiatric disease?
In the tree model of brain disease reduction in dendritic spine density in the frontal lobes is correlated with the development of the main groups of “feelbad feelings” namely
There is hypersensitivity to these feelings and usually some form of obsessive-compulsive behaviour.
Bright artificial light is known to improve the symptoms of
Depression – excessive self-pity
Bulemia – obsession-compulsion with weight often associated with anxiety (excessive fear) and depression (excessive self-pity)
Pre-menstrual symptoms – combination of anxiety (excessive fear), depression (excessive self-pity) and hatred (excessive resentment).
Parkinson`s disease (excessive tremor)
This would fit in with light reducing the immunogenic response and subsequently increasing dendritic spine density i.e. reduction in dendritis.
If light also reduces the immunogenic response due to increased TREG and reduced macrophage (similar cells to microglia) activity in the skin this would explain why sunlight/light therapy improves the following inflammatory skin disorders
The study confirming the interaction between the immune system and dendritic spines and the effect of light/darkness on the interaction in health is novel. However the study did not measure brain TREG cell activity following exposure to excessive light and darkness. Perhaps a further study could measure brain TREG cell activity with excessive light/darkness exposure. It is anticipated that brain TREGS would
Increase with light exposure
Decrease with darkness.
Decreased brain TREG activity is associated with an increased immunogenic response within the brain resulting in dendritis and subsequent psychiatric and neurologic disease. Light therapy for these conditions should be further studied.
One further point is that in psychiatric disease, and in particular dependency, “bad” visual images provoke “feelbad” feelings and “good” visual images provoke “feelgood” feelings.
Perhaps the effects of exposure to such “good” and “bad” visual images on the interaction between the immune system and dendritic spines could be studied.
In the case of laboratory mice the following images could be used
“Good” visual image – cheese slice.
“Bad” visual image – a cat.
Light should be added to the list of things that make dendritic spines grow.
The phrases “he came to see the light” and “seeing light at the end of the tunnel” take on whole new meanings as we learn more about the interaction between light and the brain.
Microglial Interactions with Synapses Are Modulated by Visual Experience. Majewska et al PloS Biology (November 2010).