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Preventive Medicine 2018 Journal of Preventive Medicine
ISSN: 2572-5483 Page 56
July 16-17, 2018
London, UK
9th Edition of International Conference on
Preventive Medicine
& Public Health
As a member of the Fos family proteins and belonging to the
IEGs (Immediate Early Genes), the ~33kD transcription factor
ΔFosB, is initiated by a wide range of effects such as drugs of
abuse or other psychoactive substances, but also external stimuli
of manifold nature. ΔFosB forms heterodimers with Jun proteins,
to form active activator protein-1 (AP-1) complexes, binding then
to AP-1 sites in the promoter regions of many neural genes. To
date, several downstream target genes for ΔFosB have been
identified, including NMDAR1, GluR2, Cdk5, and NF-kB, being
involved in molecular pathways concerning addictive behavior.
Chronically recurring exposures to stimulant interactions induce
a displacement of the rather unstable ~33kD transcription
factor ΔFosB by highly robust ~35-37kD isoforms; leading
to consistent accumulation of these stable ΔFosB derivates
particularly in the nucleus accumbens (NAc), a key region in the
reward center of the brain, and hippocampus (HPC). These inert
~35-37kD ∆FosB derivatives linger there for several weeks, even
after cessation of excitations. A fact seeming to be responsible
for the development of sustained neuronal plasticity. Here, we
demonstrate the presence of ~35-37kD ΔFosB isoforms in the
NAc and HPC of chronic drug abusers via immunoblotting and
immunohistochemistry. Moreover, this protein was characterized
by means of mass spectrometry to elucidate potential additional
phosphorylation sites, seeming to accelerate the factors stability.
Our findings provide additional evidence of the potential impact
of ∆FosB on its downstream targets, which are responsible for
long-term effects and serious adaptations in the brain leading to
addictive behavior.
Biography
Monika Heidemarie Seltenhammer completed her DVM and PhD from
VMU in Austria and Postdoctoral studies from Veterinary University of Vi-
enna, 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 ForensicMedi-
cine of the Medical University Vienna, where she specializes in Neurobiology
and Addiction Behavior.
Accumulation of stable ~35-37kD ∆FosB isoforms in the
reward system of chronic drug abusers: The key factor of high
relapse rate?
Monika Heidemarie Seltenhammer1, Ulrike Resch2, Friedrich Altmann 3, Johann
Sölkner4 and Daniele Ugo Risser1
1Center for Forensic Medicine - Medical University of Vienna, Austria
2Centre of Physiology and Phamacology - Medical University of Vienna, Austria
3University of Natural Resources and Life Sciences, Austria
4NUWI - BOKU, Austria
Monika Heidemarie Seltenhammer et al., J Prev Med 2018, Volume 3
DOI: 10.21767/2572-5483-C1-003
Figure 1: Schematic presentation of full length
FosB vs ΔFosB with known phosphorylation sites.