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The development of the dendritic tree of a neuron is a complex process which is thought to be regulated strongly by signals from afferent fibers. In particular the synaptic activity of afferent fibers and activity-dependent signaling by neurotrophic factors are thought to affect dendritic growth. We have studied Purkinje cell dendritic arbor development in organotypic cultures under suppression of glutamate-mediated excitatory neurotransmission, achieved with multiple combinations of blockers of glutamate receptors. Despite the presence of either single receptor blockers or combinations of blockers predicted to fully suppress glutamate-mediated excitatory neurotransmission Purkinje cell dendritic arbors developed similar to those of control cultures. Furthermore, Purkinje cell dendritic arbors in organotypic cultures from brain-derived neurotrophic factor (BDNF) knockout mice or after pharmacological blockade of trk-receptors also developed in a way similar to control cultures. Our results demonstrate that during the stage of rapid dendritic arbor growth signals from afferent fibers are of minor importance for Purkinje cell dendritic development because a seemingly normal Purkinje cell dendritic tree developed in the absence of excitatory neurotransmission and BDNF signaling. Our results suggest that many aspects of Purkinje cell dendritic development can be achieved by an intrinsic growth program. [Copyright &y& Elsevier]

Abstract: A variety of neurological diseases are characterized by disturbances of the blood–brain barrier (BBB) and its transporters. We recently introduced fibroblast growth factor treated cortical organotypic slice cultures of mice as a model for in vitro studies of the blood–brain barrier and have now further characterized the maintenance and function of transport-proteins typically expressed in the endothelium of cerebral blood vessels. The glucose transporter GLUT-1 is present in blood vessels of slice cultures derived from postnatal day 4 to 21 mice after 3 days in vitro . The endothelial multidrug resistance P-glycoprotein (P-gp) which is involved in the control of pharmacological substance transport across the blood–brain barrier is also maintained in blood vessels, most prominently in slice cultures derived from postnatal day 14 and 21 mice. To assess P-gp function, we tested rhodamine 123 transport in presence or absence of the P-gp inhibitor verapamil. Rhodamine 123-fluorescence accumulated rapidly in the vascular lumen both in acute slices and in slices cultured for 3 days in vitro . Our results provide evidence that endothelial transporters and their functional properties can be maintained in organotypic cortical slices cultures, thus making it an attractive model system for the study of the blood–brain barrier. [ABSTRACT FROM AUTHOR]