Products of the Doublecortin Like Kinase (DCLK) gene are implicated in cortical migration and hippocampal maturation during embryogenesis. However, one of its splice variants, called CaMK Related... Show moreProducts of the Doublecortin Like Kinase (DCLK) gene are implicated in cortical migration and hippocampal maturation during embryogenesis. However, one of its splice variants, called CaMK Related Peptide (CARP), is expressed during adulthood in response to neurological stimuli, such as kainic acid-induced seizures and BDNF-LTP. The function of this transcript of the DCLK gene is poorly understood. To elucidate its function during adulthood we have created transgenic mice with over-expression of CARP in the brain. To study potential functions of CARP in the hippocampus we performed an electrophysiological characterization of the CA3/CA1 network of transgenic and wild-type mice and showed that field excitatory post synaptic potentials (fEPSPs) are highly increased in transgenic mice, while population spike amplitudes (PSAs) remained equal between genotypes. Consequently, hippocampal CA3/CA1 network excitability was decreased in transgenic mice. In addition we show a 2-fold up-regulation of the Ca2+-binding protein calretinin and a down-regulation of Rapgef4, a guanine exchange factor for Rap1, in the hippocam pus. Given previously established conditions during which CARP is induced and our current data, we propose that this DCLK gene product affects glutamatergic neuronal transmission in response to neurological stimuli. (C) 2010 Elsevier B.V. All rights reserved. Show less
This thesis describes the process of neuronal differentiation of Ns-1 PC12 cells in response to Nerve Growth Factor (NGF) treatment. By means of DNA microrrays, genome-wide transcriptional... Show moreThis thesis describes the process of neuronal differentiation of Ns-1 PC12 cells in response to Nerve Growth Factor (NGF) treatment. By means of DNA microrrays, genome-wide transcriptional profiling was performed during the initial 2 hours of NGF-treatment and during the initial 4 days of NGF-treatment. In the first case 5 previously unrecognized NGF-responsive immediate-early genes were discovered and in the second case, nearly 1600 NGF-responsive delayed-response genes were measured. Particularly, DCLK-short appeared to be a highly responsive transcript during NGF-induced neuronal differentiation of Ns-1 PC12 cells. The function of its corresponding protein was investigated and shown to mediate neuronal outgrowth of these cells, in a phosphorylation-dependent manner. Moreover, the molecular pathways underlying its basal and induced expression were analysed. Show less
