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Abstract

As already extensively proofed with reams of animal experiments, but also recently shown in humans, the 33kD transcription factor FosB, a member of the Fos family proteins and belonging to the IEGs (Immediate Early Genes), is initiated by varying effects such as drugs of abuse or other psychoactive substances, and psychotherapeutic agents, in the acute phase. Chronic exposure to these interactions leads to the displacement of the unstable 33kD to highly robust 35-37kD isoforms. This in turn maintains to a consistent accumulation of these highly stable FosB derivates in the nucleus accumbens (NAc), the reward center of the brain, insistently persisting there for months and beyond following cessation of the chronic stimulus - a major fact that seems to be responsible for the development of sustained neuronal plasticity. In case of long-term drug abuse, it ultimately leads to addictive behavior. Focused on this, we demonstrate the presence of accumulated 35-37kD FosB isoforms in the NAc of chronic drug-sick deceased people with pronounced long-term opioid abuse anamnesis via immunoblotting. Similar results we can present by immunohistochemistry. Further, this protein was characterized by means of Mass Spectrometry to elucidate potential additional phosphorylation sites, seeming to accelerate the factors stability. Our current results emphasize the remarkable high resistance of this phosphorylated transcription factor. The data confirm the strong impact of FosB and its downstream transcriptional targets with regard to long-term biological consequences for and potentially fatal adaptations of the brain leading to addictive behavior and high relapse rates in response to chronic drug abuse. As a consequence, when thinking about establishment and interpretation of sensitive biomarkers on the one hand, and development of novel therapeutic strategies in terms of psychological disorders in general and especially in (drug) addiction on the other hand, this strong impact of FosB should be in our mind.

Biography

Monika H Seltenhammer completed her VMD and Ph.D. from VMU in Austria and post-doctoral studies from Veterinary University of Vienna, Max Perutz Laboratories and Medical University of Vienna in Austria, where her core area of scientific work mainly consisted in cancer research (melanoma) and pathology, but also immunology, neurology and virology. She has received several honor and awards. She is a leading member of the scientific staff of Dr. Daniele Ugo Risser at the Department of Forensic Medicine of the Medical University Vienna, where she specializes in neurobiology and addiction behavior.