Due articoli sulla presunta origine della schizofrenia, portati al 2000 Society for Neuroscience Annual Meeting, la Conferenza della Societa' Americana di Neuroscienze

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NEURON LOSS DURING ADULTHOOD FOLLOWING PRENATAL LOW-DOSE X-IRRADIATION IN THE MOUSE BRAIN--IMPLICATIONS FOR THE PATHOGENESIS OF SCHIZOPHRENIA?

H. Korr1; S.W. Schoen2*; C. Schmitz1

1. Dept Anat Cell Biol, RWTH Univ Aachen, Aachen, Germany

2. Dept Neurol, RWTH Univ Aachen, Aachen, Germany

Prenatal low-dose X-irradiation (PLDI) results in cell death in the fetal telencephalon, most probably mediated by nuclear (n) and mitochondrial (mt) DNA damage. However, it is unknown whether there are long-term consequences of PLDI on postnatal nDNA and mtDNA of neurons, and whether this is connected with a reduction of neuron numbers in the adult brain. Therefore, mice were X-irradiated with either 0 cGy, 10 cGy or 50 cGy at day 13 of pregnancy. One day later, or postnatally at day 25 (P25) or P180, the rate of nDNA repair was investigated via unscheduled DNA synthesis after injection of 3H-thymidine in vivo. The relative content of DNA single strand breaks (SSB) was determined by in situ nick translation. MtDNA synthesis, representing mt biogenesis, was measured via cytoplasmic labeling after injection of 3H-thymidine. Total numbers of neurons were estimated with modern stereology in several brain areas. One day after irradiation no unrepaired SSB could be detected. Howeve! r, at P25 neurons of distinct areas showed an increased content of SSB and increased mt biogenesis. At P180, the most remarkable result was a significant loss of hippocampal pyramidal cells after 50 cGy PLDI. Most probably this neuron loss was connected with impaired mitochondrial function, resulting in an ongoing discrepancy between increasing nDNA damage and failure to provide energy for repairing this damage. This is the first report of a second, postnatal wave of cell death following PLDI. Possible impact of these data on the neurodegenerative hypothesis of schizophrenia is discussed. Supported by: EC/NRPB

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PERINATAL ASPHYXIA INDUCES EARLY NEURODEGENERATIVE PROCESSES INVOLVING HIPPOCAMPAL NEURON LOSS AND CYTO-ARCHITECTONAL CHANGES RELATED TO SCHIZOPHRENIC PATHOPHYSIOLOGY.

W.D. Van de Berg1,2; C. Schmitz3; H.E. Steinbusch2; D. Schuster3; C.E. Blanco1; H.W.M. Steinbusch2

1. Pediatrics, GROW, Maastricht, Netherlands

2. Psychiatry, Brain&Behavior, Maastricht, Netherlands

3. Anatomy Cell Biology, RWTH, Aachen, Germany

Schizophrenia is a neurological brain disorder, which origin is still unknown. Recently, theories have emphasized the role of abnormal neurodevelopment and early neurodegenerative processes in the pathophysiology of schizophrenia. It is believed that insults occurring long before the onset of the schizophrenia disrupt normal brain development, resulting in cyto-architectonal changes and decreased number of neurons in striatum and hippocampus. In a rat model, we show that asphyxia at the time of birth, induced by immersing fetus-containing uterus horns in a water bath at 37°C for 20 min, generates neuronal loss in the hippocampus (17.5%) and a reduction in hippocampal volume (9.1%), 21 days after birth. Furthermore, perinatal asphyxia resulted in increased lateral ventricles and striatal volume and reduced area of the cerebral cortex at P21. To determine if the neuronal loss was a consequence of disturbed development or a neurodegenerative process, we quantified the number of T! UNEL and Caspase-3 positive profiles in the hippocampus. We found signs for developmental apoptosis at P2 and P8 in control animals, which was increased in asphyctic animals. No astrogliosis was found at these time points. These findings indicate that perinatal asphyxia leads to an early neurodegenerative process resulting in neuronal loss and architectonal changes. Furthermore, they could provide new evidence for a correlation between the reported anatomical changes in schizophrenic patients and early insults as perinatal asphyxia.