Professor, Department of Neurology and Neurosurgery
McGill University, Canada
Biochemical processes in the central nervous system (CNS) are hard to investigate, due to the unavailability of samples from the CNS in the in vivo investigations. There are only a few direct methods that enable us to determine the biochemical processes in the human brain during its life span. Today, basic studies in the field of radiochemistry have been found in the investigation of the biochemical processes in the CNS. Mirko Diksic is a scientist who has successfully used his abundant experience in basic sciences and applied that knowledge to neurobiological and neuropharmacological research.
His work has been cited in more than 7000 scientific articles and papers around the world. He has been a guest of numerous international institutions and scientific meetings, has travelled around the world and has been a guest lecturer over 100 times. After joining the Montreal Neurological Institute in 1979 Mirko Diksic, along with a research group, devised and set up the first medical cyclotron facility in Canada designed exclusively for medical research. The cyclotron was opened in 1981, and was used very successfully for research until 1991, when it was replaced with a new and improved machine still used today. He made a substantial contribution to the development of the methods for the synthesis of radioactive labeled compounds used medical research. At the same time, Mirko Diksic established a radiochemical laboratory to prepare biologically active molecules marked with the short living 18F md 11C radioisotopes. These labeled molecules have been used in investigations of processes in the human CNS in vivo using PET. Mirko Diksic made a significant contribution to oncological brain research. Soon after the installation of the cyclotron, one of the first radioactively labeled radiopharmaceuticals was a drug named Carmustine (1,3 di-chloroethylen nitrosourea, BCNU), that is often used in the treatment of brain tumors. Mirko Diksic was the first person to demonstrate that the effects of BCNU depend on its routes of administration. Using PET studies, it was determined that 11C-BCNU following intra-arterial administration accumulated in brain tumors 50% more than after intravenous administration. A great deal of Mirko Diksic's scientific work is connected to studies in the control of the synthesis rate of the neurotransmitter (serotonin) in the CNS. It is assumed that alterations of the serotonergic system in the brain are related to psychiatric disorders such as depression, schizophrenia, eating disorders and substance abuse disorders (alcoholism). At the end of the 20th Century Mirko Diksic, together with associates from both Japan and Croatia, investigated the effects of psychotropic drugs that produce their effects via the serotonergic system, on the rate of serotonin synthesis.
It has been shown that the anorectic drug fenfluramine and the antidepressant drug fluoxetine (better known as »Prozac«) increase the rate of serotonin synthesis in nerve terminal regions (cortices, striatum, hippocampus), while they simultaneously decrease the rate of serotonin synthesis in the regions of the serotonergic cell bodies. Furthermore, the effect seems to be different after acute and chronic administration. The obtained data indicated that alterations of serotonergic receptors activity may be one of the factors involved in the regulation of serotonin synthesis. Mirko Diksic is one of the first scientists to determine the rate of serotonin synthesis in the human brain in vivo, using 11C-alpha-methyltryptophan synthesized in his own laboratory. The most significant contribution of this study was the finding that the rate of serotonin synthesis in healthy male and female brains is differently affected by mild »stress« produced by lowering body tryptophan, and that there is a region specific changes between normal subjects and those suffering from affective disorders.