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Item does not contain fulltext Mounting evidence suggests involvement of prenatal factors in the pathogenesis of schizophrenia. The objective of the present study was to provide evidence for the hypothesis on schizophrenia that abnormal fetal brain development leads to impaired sensorimotor gating of acoustic startle stimuli. To this purpose, pregnant rats were treated with methylazoxymethanol acetate on one of four subsequent days of gestation, from E9 to E12. These procedures inhibit early stages of cortical proliferation in the foetuses, resulting in early abnormalities that were mainly found in the entorhinal region. At the adult age, habituation and prepulse inhibition (PPI) of startle responses to acoustic stimuli were investigated. Our results show impaired habituation and PPI in rats treated at embryonic days 10 and 11. It is concluded that sensorimotor gating deficits can result from a developmental abnormality involving the entorhinal region, supporting the hypothesis that similar deficits, often observed in schizophrenic subjects may be the result of entorhinal cortex dysfunction.

Depression and schizophrenia are major psychiatric disorders. Recently it has been documented that these diseases are characterized by deficits and / or loss of neurons in specific brain regions. Nerve growth factor and brainderived neurotrophic factor are endogenous biological mediators involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system. Structural, biochemical, and molecular findings led to the hypothesis that these molecules play a role in the pathophysiology of psychiatric disorders and suggested that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity both in young, adult and aged subjects. Studies aimed at understanding the mechanisms regulating these events might be an important line of research for analyzing the etiopathogenesis of psychiatric disorders and eventually identifying new methods for diagnosis and new therapeutic strategies.

We previously reported that prenatal methylazoxymethanol (MAM) administered on days I I and 12 of rat pregnancy induces structural changes in the cytoarchitecture of the hippocampal-entorhinal axis. We also showed that young and middle-aged prenatally treated MAM animals displayed changes in brain neurotrophin levels [Neurosci. Lett. 309 (2001) 113; Physiol. Behav. 71 (2000) 57.]. To continue this line of investigation, the working hypothesis adopted was that prenatal MAM administration, by interfering with limbic neurogenesis, could impair learning and memory ability of aged animals in the water maze. It was found that injection of NIAM during early rat brain development induced deficits in both the acquisition and retention phases of the Morris maze. These behavioral changes were associated with significant changes in brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), reduced choline acetyltransferase (ChAT) immunoreactivity in forebrain cholinergic neurons and loss of neuropeptide Y (NPY) immunodistribution in cells of the entorhinal cortex. This finding, as well as confirming previous studies showing that injection of prenatal MAM administration induces significant changes in hippocampal-entorhinal axis neurogenesis and marked behavioral deficits in adult life, provides additional experimental evidence supporting the hypothesis that loss of NGF and/or BDNF-receptive or producing cells can co-occur at the onset of neurodevelopmental disorders. (C) 2002 Published by Elsevier Science Inc.

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Modern neuroimaging technology allows to Study degenerative processes in vivo and has been applied to several clinical conditions. The purpose of the present contribution is to summarize the potential of positron and single photon emission tomography (PET and SPECT, resp.), imaging, spectroscopy, apparent diffusion related and functional magnetic resonance (MRI, MRS, dMR and fMR, resp.). The time course of the development of brain damage is described in general terms, showing that the degeneration or the loss of function of neurons is most often preceded by inflammatory processes, with or without participation of the peripheral immune system. In several neuropsychiatric diseases the most optimal technology is indicated to visualize the ongoing pathological process at a particular phase of the degeneration.

Because tricyclic antidepressants (TAD) are usually given chronically to patients, both their acute and their chronic effects on 5-hydroxytryptamine (5-HT) metabolism were studied. The probenecid method was used and, in addition to 5-hydroxy-indoleacetic acid (5-HIAA), some other indole compounds in brain were measured. Simultaneously, TAD levels in brain and plasma were determined. Dimethylated as well as monomethylated TADs were administered, both at 10 and 25 mg/kg i.p. Treatment with either 10 mg/kg during 14 days or 25 mg/kg given acutely resulted in a similar brain level of TAD, so any differences found could be attributed to differences in administration schedule. Drug levels in brain and plasma differed considerably after chronic and acute treatments but no major differences in the effect on 5-HIAA level in the brain were found, although accumulation of 5-HIAA following probenecid treatment was mostly lowered after treatment with dimethylated TAD. The TAD level in rat brain was not decisive for the effect on central 5-HT turnover. The monomethylated TAD affected the 5-HT turnover very little, not only acutely but also chronically.

Synaptosomal fractions from mammalian brain were extensively used in the late sixties and early seventies to examine the existence of a local system of protein synthesis in the nerve terminals pinched off from CNS axons during the homogenization step (1-7). Despite a wealth of initial encouraging findings, this field of research was progressively abandoned as a result of growing criticism which mainly concerned the issue of contamination of the synaptosomal fractions by subcellular organelles and other cell fragments. The failure to resolve these experimental problems significantly strengthened the view that protein synthesis did not occur in the axon and nerve terminals, but only in neuronal perikarya and large dendrites.