Neuropediatrics 2012; 43 - WS17_03
DOI: 10.1055/s-0032-1307170

Age dependent regulation of the neuroprotective factor activin in the mouse brain

F Brackmann 1, M Richter 1, A Link 2, C Alzheimer 2, R Trollmann 1
  • 1Department of Pediatrics, University of Erlangen, Erlangen, Germany
  • 2Institute for Physiology and Pathophysiology, Erlangen, Germany

Aims: Activin A, a multifunctional regulatory protein of the TGF- β family, gathers more and more attention as a potential neuroprotective agent [2]. Increased cerebral expression of activin A has been observed in animal models after hypoxic-ischemic insults. Of note, neuroprotective effects of exogenous activin after hypoxic-ischemic and kainat-induced injury have been shown in the adult rodent brain [1]. In addition, elevated serum activin A levels have been observed in asphyxiated newborns. The present study investigated mechanisms of hypoxic regulation of activin A in developing mouse brain.

Methods: Primary embryonal neuronal cell cultures (DIV1/DIV6/DIV12; days in vitro) were exposed to hypoxia (1% O2) and normoxia (21% O2) for an incubation interval of 4h. In vivo model: C57BL6 mice (P0-P10) were exposed to normoxia and systemic hypoxia (8% O2, 6h; Hypoxic Workstation INVIVO2 400). Quantification of specific cerebral mRNA expression by real time PCR (n ≥3).

Results: In vitro analysis showed a significant decrease of activin A mRNA levels of DIV1 and DIV6 neuronal cultures (p<0.05) under hypoxia compared to normoxia. In vivo, at P0, P7 and P10 no significant changes in mRNA expression of activin A, activin receptors (ActRIIA, ActRIIB, ActRIB) or functional antagonists inhibin and follistatin were obvious after 6h of hypoxia. VEGF, a well known hypoxia-regulated factor, was strongly induced in vitro and in vivo in response to systemic hypoxia. Moreover, we observed a significant decrease of cerebral activin mRNA levels upon a hypoxic exposure of 4h (P10, p<0.05) indicating temporal dynamic changes in relation to the degree of hypoxia.

Conclusion: In contrast to results on adult rodent brain, present analysis did not confirm hypoxia-induced overexpression of activin A in the developing mouse brain indicating age-specific regulatory pathways of the activin system. Further functional analyses of the activin system are necessary and are subject of our ongoing studies on transgenic animals with dominant negative activin receptors.

activin - hypoxia - neuroprotection