Research on alcohol and drug-related changes in the central nervous system

On 6 October at 17:00 in an open meeting of the Medical Promotion Council of Rīga Stradiņš University which will be held in the Hippocrates lecture theatre, Rīga, 16 Dzirciema St., Sandra Skuja will defend her doctoral thesis “Morphological Investigation of Alcohol and Drug-Related Changes in the Central Nervous System”.

Psychoactive substances-induced damage causes dysfunction of selected brain regions. Alcohol and addictive substances and oxidative stress associated with them are widespread contributors to brain damage. Matrix metalloproteinases (MMP) involved in the cleavage of extracellular matrix (ECM) proteins are extensively analysed in brain pathology studies. However, MMPs have not been sufficiently investigated in cases of chronic alcohol and drug consumption. Recent results showed involvement of multifunctional inductive factors in CNS changes caused by alcohol and drug addiction.

A role of MMP9 in the injury and remodelling of extracellular space of brain via mediating cleavage of ECM components was specified in this study. Alcoholics and drug users revealed statistically significant elevation of neuronal MMP9 expression in all brain regions studied.

Contribution of MMP9 to these alterations was evidenced in alcoholics and drug users and correlated with ultrastructural changes. The study showed that oxidative stress caused by alcohol is one of the most important contributors to the changes of the endogenous antioxidant system and protective reactivity of neural and hepatic constituents reflected by cytoskeleton, mitochondria, and intracellular membrane changes.

Immunohistochemically assessed heterogeneous expression of inductive factors was determined in the cortex cerebri and substantia nigra regions and correlated with results obtained by electron microscopy examination. It was discovered that neuronal somata does not display irreversible changes evident in dendritic tree and glial cells. The author suggests that these behavioural differences are related to the selective response to alcohol and drug addiction-induced injury in the central nervous system. This selective reaction was proven by a decrease of SOD1 immunoreactivity in the white matter of the substantia nigra was accompanied by severe damage of myelin structure revealed electron microscopically.