Loss of the serum response factor in the dopaminesystem leads to hyperactivity

Rodriguez Parkitna, JGerman Cancer Research Center, Heidelberg, Germany (author)

The serum response factor (SRF) is a key regulator of neural development and cellular plasticity, which enables it to act as a regulator of long-term adaptations in neurons. Here we performed a comprehensive analysis of SRF function in the murine dopamine system. We found that loss of SRF in dopaminoceptive, but not dopaminergic, neurons is responsible for the development of a hyperactivity syndrome, characterized by reduced body weight into adulthood, enhanced motor activity, and deficits in habituation processes. Most important, the hyperactivity also develops when the ablation of SRF is induced in adult animals. On the molecular level, the loss of SRF in dopaminoceptive cells is associated with altered expression of neuronal plasticity-related genes, in particular transcripts involved in calcium ion binding, formation of the cytoskeleton, and transcripts encoding neuropeptide precursors. Furthermore, abrogation of SRF causes specific deficits in activity-dependent transcription, especially a complete lack of psychostimulant-induced expression of the Egr genes. We inferred that alterations in SRFdependent gene expression underlie the observed hyperactive behavior. Thus, SRF depletion in dopaminoceptive neurons might trigger molecular mechanisms responsible for development of psychopathological conditions involving hyperactivity.

Bilbao, ACentral Institute of Mental Health, (author)
Rieker, CGerman Cancer Research Center, Heidelberg, Germany (author)
Engblom, DavidLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)daven69 (author)
Piechota, MInstitute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland (author)
Nordheim, ATübingen University, Tübingen, Germany (author)
Spanagel, RCentral Institute of Mental Health, (author)
Schütz, GGerman Cancer Research Center, Heidelberg, Germany (author)
German Cancer Research Center, Heidelberg, GermanyCentral Institute of Mental Health, (creator_code:org_t)

In:The FASEB Journal: Federation of American Societies for Experimental Biology24, s. 2427-24350892-66381530-6860

By the author/editor: Rodriguez Parkit ...; Bilbao, A; Rieker, C; Engblom, David; Piechota, M; Nordheim, A; show more...; Spanagel, R; Schütz, G; show less...

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