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How our brain changes as we grow old: the Blood Brain Barrier breakdown

Updated Friday, 3 February 2023
What's the Blood Brain Barrier and how does studying this help us to find out more about diseases associated with ageing such as Alzheimer’s? OU research student, Eduardo Frias-Anaya explains:

Brain and homeostasis

microvessels in the blood brain barrier Figure 1: Tight junctions between brain endothelial cells control the transport across the barrier The brain acts as the centre of the nervous system, controlling processes occurring at different levels in the body. The structure of the brain is complex and any disturbance can lead to alterations that would affect its functions in several ways. 

Our brain needs to obtain solutes and nutrients from the circulatory system, as well as to eliminate waste products derived from metabolism. This homeostasis regulation is possible due to the presence of the Blood Brain Barrier (BBB), a dynamic interface conformed by several specialised cell types that separates nervous system from circulatory system that transports blood around the brain, mainly conformed by very small blood vessels called microvessels (fig 1). The BBB acts as a gatekeeper to regulate what molecules and compounds travel from the blood into the brain tissue. Therefore, the BBB is highly selective and restricts the passage of molecules by acting as a true physical barrier due to the close interconnections (known as ‘tight junctions’) that are formed between endothelial cells that line brain’s microvessels. The tight junctions allow the endothelial cells to form a continuous layer, preventing any leakage from the bloodstream into the brain. Most of the molecules need to be taken up by the endothelial cells of the BBB, pass across them and be released on the other side of the cell, in order to pass from the blood to the cerebral tissue. A certain number of membrane proteins and transporters are expressed on the surface of these brain endothelial cells in order to form the junctional structures, as well as control the traffic of compounds. These membrane elements are supported by the role of the so-called adaptors, different kind of proteins also expressed in the membrane and cytosol of brain endothelial cells that can mediate in cell to cell contacts and transport of molecules across the barrier.

Alterations during ageing

The female ageing process Figure 2: The process of ageing is a normal phenomenon that occurs in every individual The BBB can be altered under several circumstances such as the normal process of ageing (fig 2.). The BBB breakdown is an early phenomenon in ageing, and one of the most important alterations is the loosening of the tight junctions, which leads to an increase in permeability, allowing molecules and blood pass from the microvessels to the brain. Therefore, these changes can lead to neurovascular incidents such as stroke and can enhance pathological processes as Alzheimer’s disease or Multiple Sclerosis. According to previous studies, age-related structural and functional changes in the BBB seem to be associated with an altered gene expression. It also has been shown that postmenopausal women are at greater risk of developing neurovascular incidents than similarly aged men. However, there is a lack of information about the decline of BBB in women since most of the data available was obtained studying men.

In conclusion, researching the dysfunction of the BBB during ageing in females is an essential step to understand the mechanisms underlying several age-related conditions. It also will help us to find new treatments against some of the most important neurological pathologies.

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