DECEMBER , 2023 | THE HEALTH

BRAIN BITES

BY DR WAEL MY MOHAMED

In contrast to the conventional belief that demyelination mostly results in axon degeneration , the research discovered that axons encased in faulty myelin are more susceptible to damage . The study team found that in animal models of uncommon disorders with myelin protein abnormalities , defective myelin attracts cytotoxic T cells , resulting in inflammation .

Unexpectedly , axons lacking myelin had a higher likelihood of survival . This study emphasises the intricate involvement of immune responses in myelin disorders and proposes novel treatment targets that regulate immune system function to save neurons .

The work contradicts the conventional perspective that demyelination is only harmful , demonstrating that axons with aberrant myelin are more susceptible to danger . The text elucidates cytotoxic T cells ’ function in attacking defective myelin , resulting in a beneficial loss of myelin for some axons . The results provide novel perspectives on therapeutic approaches for myelin disorders , highlighting the need of therapies that maintain a delicate equilibrium in immune reactions .

Myelin is a lipid and protein-based insulating covering that surrounds axons , which are the connections between nerve cells . It facilitates the rapid transmission of electrical impulses and maintains the structural and operational integrity of neurons . Oligodendrocytes , specialised glial cells , are responsible for myelin formation in the central nervous system . Myelinated fibre tracts are especially susceptible to many diseasecausing processes , and myelin disorders are often linked to long-lasting inflammation of the nervous system .

An exemplary instance is multiple sclerosis , a prevalent and severe neurological disorder characterised by immune cells causing demyelination , which refers to the degradation of myelin . Nevertheless , dysfunctional immune responses also play a role in other conditions linked to abnormalities in myelin , such as inherited and age-related illnesses .

Crucially , the deterioration of axons and neurons significantly determines the degree of clinical illness in these conditions . It is often believed that as myelin is lost , the exposed axons become more susceptible to a harmful inflammatory environment , eventually leading to their death .

MYELIN ANOMALIES AND THE THREAT OF AXONAL BREAKDOWN

The researchers examined animal

models of uncommon disorders that exhibited abnormalities in the primary myelin protein of the central nervous system to explore the correlation between myelin loss and axon degeneration . The models of uncommon monogenetic illnesses have distinct possibilities to uncover processes that have wide applicability for more common ailments .

Previously , the scientists found that the presence of defective or “ dysfunctional ” myelin in these animals triggers an inflammatory response characterised by the build-up of cytotoxic CD8 + T cells . Within the examined disease models , these adaptive immune cells selectively attack and impair fibre segments with defective myelin , resembling the characteristics of multiple sclerosis .

Contrary to the commonly held belief , they discovered a reverse correlation between the loss of axons and demyelination when comparing the illness models . Fibres that maintained myelin despite the persistent assault of T cells exhibited an increased susceptibility to degeneration , while those with demyelination survived . Furthermore , the mice ’ s behavioural impairments had a stronger correlation with neurodegeneration rather than demyelination .

Microglia are innate immune cells that reside in the central nervous system and have the ability to coordinate both harmful and helpful immune responses . In their research , the authors used several pharmacological methods

Dr Wael MY Mohamed is with the Department of Basic Medical Science , Kulliyyah of Medicine , International Islamic University Malaysia ( IIUM ). to manipulate the elimination of aberrant myelin by microglia .

This work demonstrates that the effective elimination of damaged myelin by microglia , in response to an adaptive immune onslaught , enables the preservation of axons during reversible phases of injury . Therefore , the continuous presence of “ bad ” myelin seems to have a more detrimental effect on neurons compared to the absence of myelin , particularly when myelin is attacked by the adaptive immune system .

OLIGODENDROCYTE ASSAULT ON AXONS : A DESTRUCTIVE DANCE

The scientists were able to determine a method by which oligodendrocytes , when assaulted by T cells , cause injury to their axonal counterparts . An abnormal constriction response was seen in the myelinating processes surrounding the axons .

By immobilising cytoskeletal filaments , they were able to decrease axon degeneration caused by abnormal constriction . The T cell onslaught seemed to stimulate oligodendrocytes to constrict axons in a manner reminiscent to a constrictor snake .

What is the biological purpose of these intricately structured but selfdestructive processes ? The researchers hypothesise that the oligodendrocytes ’ responses may have positive effects in other circumstances , such as nervous system damage .

Nevertheless , the abnormal activation of these immune-mediated processes may be detrimental in certain illnesses . The research found potential targets for therapeutic intervention in disorders characterised by myelin abnormalities and nervous system inflammation .

Furthermore , they stress the need for innovative treatment strategies for myelin illnesses that may effectively inhibit harmful immune responses while permitting good ones , such as eliminating “ harmful ” myelin . This may facilitate the development of neural resilience mechanisms as a necessary condition for recovering from nervous system trauma .

To summarise , this work reveals harmful interactions between axons , glial cells , and the immune system that contribute to the degeneration of neurons . It also suggests potential targets for therapy in conditions characterised by myelin abnormalities and neuroinflammation . This unequivocally reveals the secrets of Myelin Restoration . – The Health