Olanzapine Increases Neural Chemorepulsant—Draxin Expression in the Adult Rat Hippocampus

Abstract

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.

Electroconvulsive Therapy Reduces Protein Expression Level of EP300 and Improves Psychiatric Symptoms and Disturbance of Thought in Patients with Schizophrenia

“…17,18 Some evidence 19,20 suggests that dysregulation of adult neurogenesis is associated with psychiatric disorders such as schizophrenia. A recent study 21 found that olanzapine increased neural chemorepulsant-Draxin expression in the adult rat hippocampus, which is an inhibitory axon guiding factor and local chemorepulsive glycoprotein involved in neuronal migration and neurite growth in the developing brain. [22][23][24] Besides, it is reported 25 that in children and adolescents with a neurodevelopmental disorder or neurodevelopmental difficulties, the onset of psychosis is likely to be characterized by positive symptoms (eg, grandiose ideas, perceptual abnormalities, disorganized communication) and disorganized symptoms (eg, odd behavior or appearance, bizarre thinking), which means that the positive symptoms of SCZ may be related to neurodevelopmental disorders.…”