In 1998, a first report on neurogenesis in the hippocampal dentate gyrus of adult humans attracted tremendous attention worldwide. This report extended the findings of various animal studies over the last four decades to humans. The mechanisms involved in the regulation of postnatal and adult neurogenesis have as yet been only partly elucidated. Important factors appear to be adrenal steroids and excitatory input via NMDA receptors which both modulate proliferation, migration and survival of dentate granule neurons. Interestingly, exposure of animals to "rich environment" or to different conditions of stress has been found to significantly influence the amount of neuronal proliferation and apoptosis in the dentate gyrus. The revelation of the potential of neurons in the adult brain to proliferate and to regenerate has opened a whole new area of future therapeutic strategies for neuropsychiatric disorders. Rather than treating far progressed conditions or defective states in a symptomatic way, our efforts will have to be directed toward prophylactic approaches. Based on increasing possibilities to identify and define for instance genetic risk factors, neuroprotection will play an important role. Prerequisite for these new strategies aiming at therapeutic manipulation of quiescent neuronal stem cells in the dentate, however, will be the understanding of the discrete mechanisms initiating, regulating, or modulating neuroproliferation / neuroapoptosis (programmed cell death) in this privileged brain area.

The Symposium VI within the AGNP-Congress 1999 "The dentate gyrus: from neurogenesis to neuropsychiatric disorders" has been designed to provide a first overview of this development at the dawn of a new millennium: Neuroprotection and neuroprophylaxis as neuropsychopharmacology of the future. Scientists from different areas of expertise and different background have been asked to contribute the first parts of a mosaic which, although still incomplete, will help to visualize an imaginary picture. Gerd Kempermann will talk about "The dentate gyrus - a cradle for new neurons throughout life", and will demonstrate his exciting results showing environmental effects on neuroproliferation. Should this be a molecular mechanism explaining how psychotherapy acts? Environmental influences and, in particular, effects of psychosocial stress on neurogenesis are the topic of Eberhard Fuchs’s talk "Glucocorticoids and the dentate gyrus" which actually emphasizes the need to learn sufficient stress coping strategies in order to maintain a certain amount of basal neuroproliferation. An unexpected new role for components of the endothelin system, that has attracted much attention in recent years due to its potent vasoactive properties, will be reported by Hannelore Ehrenreich talking about "Endothelin B receptor deficiency and neuronal apoptosis in the dentate gyrus". The presence or absence of these receptors is associated with neuronal survival or apoptosis both in postnatal development and under pathological conditions like ischemia/hypoxia or meningitis. A prerequisite to switch from primarily morphological to functional observations, is to perform behavioral tests. In her paper "Functional role of the dentate gyrus tested in animal models", Ulla Havemann-Reinecke is going to describe mechanisms of conditioned learning that require major hippocampal input. Subsequently, Hanns Jürgen Kunert will provide methods of hippocampal / dentate testing for application in humans in his talk "Neuropsychology of the dentate gyrus". Last but not least, Barbara Lipska will translate the findings on the dentate gyrus to a specific disease, talking about "Hippocampal neonatal lesion as a model for schizophrenia". Fritz Henn will extend the topic to depression, reporting on "Hippocampal plasticity and depression". With the last two talks, a major aim of this symposium will be met: bridging the gap from basic research to the clinic.

(A) Spontaneous neuronal proliferation in the dentate gyrus detected by BrdU-labeling (proliferating neurons indicated by arrows) in a 4 day old rat.

(B) Apoptotic neuron in the dentate gyrus displaying the typical ultrastructural signs of chromatin condensation. Nuclear fragmentation is specifically indicated by gold particles labeling In-Situ-Tailing reactions. Gold labeling EM-Method developed by Prof. Lothar Schilling, Mannheim.

Prof. Hannelore Ehrenreich, M.D., D.V.M.,

Max-Planck-Institute for Experimental Medicine,

Hermann-Rein-Str. 3, D-37075 Göttingen, Germany.

Phone: +49-551-3899628

Fax: +49-551-3899670

E-mail: ehrenreich@exmax1.mpiem.gwdg.de