The real story of cholesterol and the brain

There has been a lot of “Hoo Ha” in the media following the airing of the program “the heart of the matter” on Catalyst recently, so  I thought this was a great opportunity to present would the brain’s perspective on cholesterol.

Pardon me, but you have a fat head.

With sixty percent of your brain being made up of fat, having access to the right fats is essential to good brain health and function.

Whilst cholesterol has been vilified over the last couple of decades as being the baddie in relation to heart health, Omega-3 by contrast has become the new pin up idol for health and wellbeing. Omega-3 is what is called an essential fatty acid, which means the body doesn’t create it and is totally dependent on our dietary intake (mostly through oily, cold water carnivorous fish) to get enough.

However cholesterol is a different story. While we obtain some cholesterol from our diet, most of the cholesterol in our body is self-manufactured.

Moreover the brain synthesises its own cholesterol and retains it, effectively shielding it from the rest of the body behind the blood brain barrier. Astrocytes, (specialized glial cells in the brain) are responsible for its manufacture and transport to our neurons by a carrier known as apolipoprotein E (ApoE).

Of all our cholesterol, 25% of the total amount is found in the brain, mostly as myelin, the fatty coating around nerve cells that speeds up the transmission of electrical impulses.

What does the brain use cholesterol for?

Cholesterol is essential for learning and memory. This is because cholesterol is a vital component to the formation of new synaptic connections between neurons.

Our ability to form new synapses is brain plasticity in action and ultimately translates into our ability to produce thoughts, to learn and remember.

To form a new synapse, extensions from neurons called dendrites grow under the direction of signaling proteins, which rely on the presence of special lipid (fatty) rafts. Without these rafts the new synapses cannot be completed.

In 2001, a study published in Science suggested that genetic or age related defects in the synthesis, transport or uptake of cholesterol in the CNS might directly impair the development and plasticity of our synaptic circuitry.

Without cholesterol we diminish our ability to learn and encode memory.

The role of sleep and memory.

Sleep is one of the essential components to brain fitness: having a brain that is optimised to perform to the best of your ability, every day.
When we sleep, genes important to the manufacture and maintenance of myelin are upregulated.
It is when we sleep that our brain sets to work consolidating memory, increasing our performance of newly acquired skills and increases plasticity.

Cholesterol, and the formation of neurons associated with dopamine

In 2009, scientists from the Karolinska Institute revealed that cholesterol is essential to the formation of neurons that produce dopamine, our reward neurotransmitter. Loss of dopaminergic neurons is associated with Parkinson’s disease.

What effect do statins (cholesterol lowering drugs) have on brain function?

Statins are a class of drugs popular since the eighties to lower plasma cholesterol as part of a strategy at reducing an individual’s risk profile for heart disease.

They have also been used in clinical trials to examine whether their use would help in clearing beta amyloid from the brain and thereby reduce an individual’s risk of Alzheimer’s disease. These studies have not confirmed any such benefit and some authors have concluded that the assumption that high brain cholesterol in the brain is associated with Alzheimer’s disease is not valid.

Whilst the blood brain barrier is highly effective at preventing the majority of drugs from crossing it, some can.
It should be noted that statins are taken to lower plasma cholesterol only, not brain cholesterol. However it has been reported that some people taking statin drugs have experienced memory loss.

So what is the message here?

The basic premise is that to achieve optimal brain health and function it is vital to consider how the brain has been designed to operate at it’s best.

Incorporating enough sleep into our daily lives would seem a good way to go, along with eating healthily, managing our stress levels and getting enough exercise.

Which leads me to the very important point made by Dr. John Abramson from Harvard medical School, Public School of Heath when making a comment at the end of the Catalyst program. He made it in the context of statins and heart disease but it makes sense when approaching health holistically.

“We’re missing the message: that health rarely comes out of a bottle.”

“Exercise and a Mediterranean-style diet is the best way to prevent heart disease. I think virtually everybody agrees with that.”

I think I would add “and keeps our brain healthy.”

What are your thoughts around cholesterol?

References:

I. Björkhem & S. Meaney. (2004) Brain Cholesterol: Long Secret Life Behind a Barrier. Arteriosclerosis, Thrombosis, and Vascular Biology. 24: 806-815
doi: 10.1161/ 01.ATV.0000120374.59826.1b

M. Orth & S Bellosta (2012) Cholesterol: It’s regulation and role in central nervous system disorders. Cholesterol Vol 2012, Article ID 292598, 19 pages
http://dx.doi.org/10.1155/2012/292598

M.D. Ledesma & C.G. Dotti (2005) The conflicting role of brain cholesterol in Alzheimer’s disease: lessons from the brain plasminogen system. Biochem Soc Symp. 2005;(72):129-38.

B. A. Barres & S. J. Smith Cholesterol–Making or Breaking the Synapse Science 9 November 2001: 1296-1297.

P. Sacchetti, K.M. Sousa, A.C. Hall, I. Liste, K. R. Steffensen, et al. (2009) Liver X Receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell, 2 October

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