JANUARY-FEBRUARY , 2023 | THE HEALTH

BRAIN BITES

BY DR WAEL MY MOHAMED

Furthermore , older persons diagnosed with Parkinson ’ s are likely to begin having awful dreams and nightmares a few years before exhibiting the disease ’ s hallmark characteristics , such as tremors , stiffness , and slow movement . In contrast , our dreams may disclose crucial information about the structure and function of our brains , making them an interesting focus for a neuroscience study .

The most frequent motor neuron illness is ALS , which is Lou Gehrig ’ s disease . People who have ALS gradually lose the capacity to initiate and regulate muscular movements , including the ability to talk , swallow and breathe .

There is no recognised treatment . However , mouse research has found a new target in the battle against this deadly disease : the brain ’ s waste disposal mechanism . Neurodegenerative illnesses , such as Parkinson ’ s , Alzheimer ’ s and multiple sclerosis , have many commonalities , even though their clinical symptoms and disease development may seem significantly different .

The prevalence of these disorders rises with age . They are persistent and progressive , resulting in the slow loss of brain tissue . Waste proteins are also accumulated in the brain .

PROTEIN CHAINS , FOLDS AND MISFOLDS

Long protein chains fold within our bodies to generate functional forms that enable them to execute specialised activities such as generating antibodies to combat infection , supporting cells , or transporting substances . This process may sometimes go wrong , resulting

in “ misfolded ” proteins that cluster together to form aggregates . Misfolded proteins can expand and break , forming seeds that spread throughout the brain and create new clusters .

The build-up of waste proteins starts early in the neurodegenerative disease process , long before symptoms and brain loss appear . We wanted to explore whether removing or reducing the distribution of these waste proteins and their seeds may prevent or decrease disease development . The glymphatic ( glial-lymphatic ) system eliminates waste from the brain , including harmful proteins .

While humans are awake , this brain-wide network of fluid-filled spaces known as Virchow-Robin spaces is essentially turned off . However , it activates during sleep to transport substances necessary for brain function and to eliminate hazardous waste . This might explain why all organisms , large and small ( even flies ), need sleep to thrive . ( whales and dolphins , interestingly , rotate their sleep across brain hemispheres , keeping the other hemisphere awake to look for predators and signalling them to breathe !)

Sleep quality deteriorates as we age , and the risk of neurological diseases such as ALS rises . Sleep problems are another prevalent symptom of ALS , and studies have shown that even one night without sleep may increase toxic waste protein build-up in the brain .

As a result , we hypothesised that glymphatic function would be compromised in ALS . Researchers turned to mice to study this . The rodents were genetically altered to express human TDP-43 , a protein linked to ALS . They were able to switch down TDP-43 protein expression in these animals by providing them antibiotic-containing chow ( doxycycline ).

When the mice are fed a regular diet , the TDP-43 expression increases and misfolded proteins accumulate . The mice develop the hallmark symptoms of ALS , such as increasing muscular weakness and brain atrophy , over time . Researchers studied glymphatic function in these animals three weeks after turning on TDP-43 expression using magnetic resonance imaging ( MRI ).

As they saw the glymphatic system at work , they discovered that TDP-43 animals exhibited lower glymphatic clearance than unmodified control mice . These variations were seen relatively early in the illness process , which is significant . As a result , the glymphatic system may be a promising therapeutic target in treating ALS .

HOW CAN WE IMPROVE GLYMPHATIC FUNCTION

Not all sleep is created equal . Sleep is divided into rapid eye movement ( REM ) sleep and non-REM sleep . Slow-wave sleep is included in this stage , when the glymphatic system is most active .

Sleep medications that improve this period may be very effective in avoiding disorders like ALS . Glymphatic clearance is also known to be affected by sleep position . Glymphatic clearance is most effective in the lateral ( or side-sleeping ) posture , as opposed to the supine ( on the back ) or prone ( front-lying ) positions , according to mouse research .

The causes for this are unknown , however , they may be related to the effects of gravity , compression , and tissue stretching . Lifestyle decisions may also aid in the improvement of glymphatic function . Omega-3 fatty acids , present in marine fish , have long been thought to be helpful to health and lessen the risk of neurological illnesses .

According to a new study , these advantages may be partly attributable to Omega-3 ’ s beneficial influence on lymphatic function . Short-term and long-term exposure to tiny quantities of alcohol was demonstrated in mice experiments to improve glymphatic function , however , excessive dosages had the reverse impact . Exercise has also been shown to be advantageous .

All of this research suggests that simple adjustments in lifestyle may increase brain waste elimination and reduce the risk of neurodegenerative illness . Following that , research should concentrate on medicines targeting the glymphatic system to aid people suffering from these terrible disorders .

Now , do you think position matters ? – The Health

Dr Wael MY Mohamed is with the Department of Basic Medical Science , Kulliyyah of Medicine , International Islamic University Malaysia ( IIUM ).