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Volga Neuroscience School 2016 Astroglial control of rhythm genesis in the brain
Fig. 1. Neurological status of experimental animals on day 3 after total cerebral ischemia modeling (standard scale of neurological status); * - statistical significance with intact animals, p<0.05, ANOVA
Thus, we have shown that GDNF (0.8 mg/kg) application normalizes the parameters of mitochondrial respiration, and activation of the cannabinoid system stimulates the mitochondrias functioning under ischemic conditions. This effect refers to the post-ischemic adaptation and could potentially serve as one of the approaches for ischemic brain injury correction.
Acknowledgements
The research was supported by grants of Russian Foundation for Basic Research № 16-34-00301, №16-04-00245 and prepared as a part of the state project "Provision Scientific Research".
Ephrin Class a Reverse Signaling Guides Callosal Axon Growth via Efna 4-Ntrk 2 Receptor Complex Downstream of Neurod 2/6
K. Yan*, O. Grishina, G. Camarero, E. Bessa, U. Günther, R. Wunderlich, I. Bormuth, V. Tarabykin
Institute of Cell- and Neurobiology, Charité - Medical University Berlin, Germany. * Presenting e-mail: kuo.yan@charite.de
Abstract. Callosal axon guidance during cerebral cortex development is complicated and far from being fully understood. Previous work in our lab has shown that basic helix loop helix transcription factors Neurod2 and Neurod6 are essential regulators for the fasciculation and guidance of callosal axons. Here we use acallosal Neurod2/6 deficient mice as a model system to selectively study callosal axon pathfinding in vivo. We identify Efna4 as transcriptional target of Neurod2/6 in developing neocortex. In utero electroporation of Efna4 into neocortical pyramidal neurons of Neurod2/6 deficient embryos is sufficient to cell-autonomously rescue callosal axon fasciculation and migration along the normal callosal path towards the midsagittal plane. Mechanistically, Efna4 forms a co-receptor complex with Ntrk2 (TrkB) in reverse signaling, and hence regulate AKT cascades in vitro and in vivo via Ntrk2's SHC-binding tyrosine. Co-electro-poration of dominant negative Ntrk2 K571N or Ntrk2 Y515F completely abolishes the ability of Efna4 to rescue callosal axon guidance in Neurod2/6 deficient mice. We also show that the Eph receptors are abundantly expressed in the cortical plate and ventricular zone, but minimally expressed in the intermediated zone (IZ) of the cortex, while ephrinA ligands are largely present on the callosal axons in the IZ. In addition, reverse signaling from extracellular domain of EphA receptors to Efna4 leads to active axonal retraction in vivo. The complementary expression and repulsive interaction of EphA receptors and ephrinA ligands suggest a permissive channel for callosal axon navigation before midline crossing. Thus, ephrinA ligands coordinate fasciculate growth and guidance of callosal axons via interaction with Ntrk2 in cis and with EphA receptors in trans.
Keywords: NeurodD2; NeurodD6; ephrin A ligands; Ntrk2; corpus callosal agenesis.
84 Opera Med Physiol 2016 Vol. 2 (S1)
