Characterization Of Accumulated 35-37kD Isoforms Of FosB Detected In Postmortem Human Brain Tissue Samples Of Chronic Drug Addicts | 30471
Journal of Addiction Research & Therapy
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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.
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.
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