Pałasz Artur, Suszka-Świtek Aleksandra, Francikowski Jacek, Krzystanek Marek, Bogus Katarzyna, Skałbania Jakub, Worthington John J, Mrzyk Inga
Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland.
Laboratory of Insect Physiology and Ethology, Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia in Katowice, 40-007 Katowice, Poland.
Pharmaceuticals (Basel). 2021 Mar 27;14(4):298. doi: 10.3390/ph14040298.
Draxin belongs to the family of inhibitory axon-guiding factors that regulate neuronal migration and axonal spreading in the developing brain. This glycoprotein has recently been considered to play an important role both in hippocampal differentiation and adult neurogenesis in the dentate gyrus. Given that it has been reported that antipsychotic drugs may affect neurite growth and neurogenesis, we have therefore investigated whether chronic treatment with olanzapine modulates draxin immunoreactivity in the adult rat hippocampus. After analysis of local fluorescence intensity, we found a significant increase of draxin immunoexpression both in the subgranular zone (SGZ) and granular zone of the rat hippocampus following long-term olanzapine administration. This study reveals, for the first time, the modulatory effect of the atypical antipsychotic medication olanzapine on expression of the novel chemorepulsive protein draxin in the context of adult neurogenesis regulation. Moreover, this is the first report dealing with pharmacological aspects of draxin signaling. An elevated draxin expression may indirectly support a recently formulated hypothesis that olanzapine may drive adult neurogenesis via paracrine draxin-related signaling. This action of draxin is a new element in the neurogenesis mechanism that may be part of the action of second-generation antipsychotics in the treatment of schizophrenia, indicating more detailed molecular studies are urgently required to fully investigate these potential novel mechanisms of neurogenesis.
Draxin属于抑制性轴突导向因子家族，该家族在发育中的大脑中调节神经元迁移和轴突伸展。这种糖蛋白最近被认为在海马分化和齿状回的成年神经发生中都起着重要作用。鉴于有报道称抗精神病药物可能影响神经突生长和神经发生，因此我们研究了长期使用奥氮平治疗是否会调节成年大鼠海马体中的Draxin免疫反应性。通过分析局部荧光强度，我们发现长期给予奥氮平后，大鼠海马体颗粒下区（SGZ）和颗粒区的Draxin免疫表达均显著增加。本研究首次揭示了非典型抗精神病药物奥氮平在成年神经发生调节背景下对新型化学排斥蛋白Draxin表达的调节作用。此外，这是第一篇涉及Draxin信号传导药理学方面的报道。Draxin表达升高可能间接支持了最近提出的一个假说，即奥氮平可能通过旁分泌的Draxin相关信号传导促进成年神经发生。Draxin的这一作用是神经发生机制中的一个新元素，可能是第二代抗精神病药物治疗精神分裂症作用的一部分，这表明迫切需要进行更详细的分子研究来全面探究这些潜在的新型神经发生机制。
