Inhibition of glycogen synthase kinase 3 beta is involved in the resistance to oxidative stress in neuronal HT22 cells.

Oxidative stress is involved in several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic reperfusion injury (stroke). We have established clones of the murine hippocampal neuronal cell line HT22, which are resistant to the oxidative stress-causing agents glutamate and hydrogen peroxide, respectively. These cell clones show a mutual cross-resistance to other oxidative stressors, but not to essentially non-oxidative neurotoxins.

Antidepressants differentially influence the transcriptional activity of the glucocorticoid receptor in vitro.

Functional normalization of the hypothalamic-pituitary-adrenal axis in depressive patients by successful treatment with antidepressants is associated with increased efficiency of corticosteroid signal transduction. Accordingly, some antidepressants have been shown to influence the activity of the glucocorticoid receptor (GR) in cultured cells. It is not clear, however, whether this is a common principle for all antidepressants throughout all classes.

Klaus Conrad (1905-1961).

Klaus Conrad (1905-1961) was an internationally known figure in the field of neuropsychology and psychopathology. He applied Gestalt psychology to give a better understanding of the aphasias, the symptomatic psychoses and incipient schizophrenia.

The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs.

It has become increasingly clear that schizophrenia does not result from the dysfunction of a single neurotransmitter system, but rather pathologic alterations of several interacting systems. Targeting of neuropeptide neuromodulator systems, capable of concomitantly regulating several transmitter systems, represents a promising approach for the development of increasingly effective and side effect-free antipsychotic drugs. Neurotensin (NT) is a neuropeptide implicated in the pathophysiology of schizophrenia that specifically modulates neurotransmitter systems previously demonstrated to be dysregulated in this disorder.

Enhanced neurotensin neurotransmission is involved in the clinically relevant behavioral effects of antipsychotic drugs: evidence from animal models of sensorimotor gating.

To date, none of the available antipsychotic drugs are curative, all have significant side-effect potential, and a receptor-binding profile predictive of superior therapeutic ability has not been determined. It has become increasingly clear that schizophrenia does not result from the dysfunction of a single neurotransmitter system, but rather from an imbalance between several interacting systems. Targeting neuropeptide neuromodulator systems that concertedly regulate all affected neurotransmitter systems could be a promising novel therapeutic approach for schizophrenia.

Activated non-neural specific T cells open the blood-brain barrier to circulating antibodies.

Previous studies have shown that activated T cells can successfully cross endothelial barriers and will accumulate in tissue which contains their specific antigen. Myelin specific T cells (e.g.

Differential expression of group I metabotropic glutamate receptors in rat spinal cord somatic and autonomic motoneurons: possible implications for the pathogenesis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of somatic, but not autonomic, motoneurons. The reason for this selective vulnerability is unknown. The pathogenesis of ALS is thought to involve glutamatergic excitotoxic mechanisms.

Comorbidity in primary care: presentation and consequences.

Comorbidity is a well-established phenomenon in depressive disorders, and it is widely agreed that the majority of depressive disorders examined in both primary care and the general population are not "pure." This article reviews comorbidity findings in general population and primary care surveys. The implications of comorbid depressive disorders are discussed in terms of their presentation and recognition in primary care, patterns of course and outcome, and associated impairments and disabilities.

The microglia/macrophage response in the neonatal rat facial nucleus following axotomy.

Microglia represent a population of brain macrophage precursor cells which are intrinsic to the CNS parenchyma. Transection of the facial nerve in the newborn rat causes death of the affected motor neurons which is accompanied by massive activation of local microglia. Many of these cells develop into macrophages as can be shown by immunocytochemistry for OX-42 and ED1.

DSM-IV alcohol disorders in a general population sample of adolescents and young adults.

Unlabelled: AIMS/DESIGNS: As part of the Early Developmental Stages of Psychopathology (EDSP) study, results from the baseline cross-sectional assessment of DSM-IV alcohol disorders are presented for a sample of 14-24-year-olds residents in Munich, Germany (N = 3021; 71% response rate).

Findings: Life-time prevalence of DSM-IV alcohol abuse (men: 15.1%; women; 4.

Smoking and nicotine dependence. Results from a sample of 14- to 24-year-olds in Germany.

Ths paper describes the distribution of dependence criteria and diagnoses in a sample of 14- to 24-year-olds from Munich, Germany (n = 3,021; 71% response rate), evaluates differences between nondependent and dependent smokers and examines associations of smoking with other substances, affective and anxiety disorders. Assessment was made using the M-CIDI. The lifetime prevalence of DSM-IV nicotine dependence in the total sample is 19%, rising to 52% among regular smokers.

Opioid reward mechanisms: a key role in drug abuse?

There is increasing evidence to implicate the mesolimbic dopamine system in the rewarding effects of drugs of abuse such as opioids, psychostimulants, and alcohol, and in addition endogenous opioids may play a key role in the underlying adaptive mechanisms. Opioid agonists with affinity for mu and delta opioid receptors are rewarding, whereas opioid agonists with affinity for kappa receptors are aversive. These opposing motivational effects are paralleled by an increase and decrease, respectively, of dopamine release in the nucleus accumbens.

Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation.

We explored expression and possible function of interferon-gamma (IFN-gamma) in cultured fetal (E15) rat dorsal root ganglion neurons combining whole cell patch-clamp electrophysiology with single cell reverse transcriptase polymerase chain reaction and confocal laser immunocytochemistry. Morphologically, we located IFN-gamma protein in the cytoplasm of the neurons in culture as well as in situ during peri- and postnatal development. Transcripts for classic IFN-gamma and for its receptor were determined in probes of cytoplasm sampled from individual cultured neurons, which had been identified by patch clamp electrophysiology.

Molecular cloning of a novel alternatively spliced nuclear protein.

Using the yeast two hybrid system, we isolated a rat cDNA (E3-3) coding for a new protein with no homology to any other protein in the database. E3-3 is ubiquitously expressed. Variants that most likely arise through alternative splicing encode truncated forms of the protein.

Population control of microglia: does apoptosis play a role?

Brain lesions, even of the most subtle type, are accompanied by the activation of microglia, the main immune cells of the brain. Microglial cells dramatically increase in number through proliferation and adhere to the injured neurons, where they displace the synaptic input. After proliferation, microglia gradually migrate into the nearby parenchyma and appear to decrease in number.

Neurotrophin release by neurotrophins: implications for activity-dependent neuronal plasticity.

Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin secretion requires mobilization of calcium from intracellular stores.

Protective mechanisms of adenosine in neurons and glial cells.

As illustrated in Figure 1, a disturbance of the intracellular Ca2+ homeostasis is thought to be a common pathogenic factor for the generation of secondary nerve cell damage that develops after brain trauma or stroke or during the course of neurodegenerative diseases. A neuronal Ca2+ overload which may result from an excessive glutamate-evoked membrane depolarization and consecutive Ca2+ influx as well as from an activation of metabotropic receptors and consecutive intracellular Ca2+ mobilization is known to have direct toxic effects on the cytoskeleton and the cell metabolism of neurons. In addition, a Ca(2+)-dependent activation of glial cells along with the loss of physiologically required mature astrocyte functions and with the acquisition of potentially neurotoxic microglial properties, has more recently been recognized as an additive pathogenic factor.

Ca2+ and Na+ permeability of high-threshold Ca2+ channels and their voltage-dependent block by Mg2+ ions in chick sensory neurones.

1. The Mg2+ block of Na+ and Ca2+ currents through high-voltage activated (HVA; L- and N-type) Ca2+ channels was studied in chick dorsal root ganglion neurones. 2.

Origin of eukaryotic programmed cell death: a consequence of aerobic metabolism?

A marked feature of eukaryotic programmed cell death is an early drop in mitochondrial transmembrane potential. This results from the opening of permeability transition pores, which are composed of adenine nucleotide translocators and mitochondrial porins. The latter share striking similarities with bacterial porins, including down-regulation of their pore size by purine nucleotides), suggesting a common origin.

Synapse specificity of long-term potentiation breaks down at short distances.

Long-term potentiation (LTP), the long-lasting increase in synaptic transmission, has been proposed to be a cellular mechanism essential for learning and memory, neuronal development, and circuit reorganization. In the original theoretical and experimental work it was assumed that only synapses that had experienced concurrent pre- and postsynaptic activity are subject to synaptic modification. It has since been shown, however, that LTP is also expressed in synapses on neighbouring neurons that have not undergone the induction procedure.

Proliferation of ramified microglia on an astrocyte monolayer: characterization of stimulatory and inhibitory cytokines.

Proliferation of ramified microglia is a common phenomenon in brain pathology, but little is known about how this is regulated. In the current study, we examined the effect of different cytokines on the proliferation of ramified microglia in vitro using a combination of autoradiography for [3H]-thymidine and immunocytochemical techniques. Ramified microglia were obtained using a 10-day co-culture on top of a confluent astrocyte monolayer.

The neurotrophin receptor p75 binds neurotrophin-3 on sympathetic neurons with high affinity and specificity.

High-affinity neurotrophin-3 (NT3) receptors have been identified on nerve growth factor (NGF)-dependent sympathetic neurons, but their occupancy by NT3 does not lead to neuronal survival. The molecular nature of these NT3 binding sites was investigated in this study. With freshly dissociated embryonic day 11 (E11) chick sympathetic neurons, cross-linking experiments revealed that the main receptor responsible for high-affinity specific binding was the neurotrophin receptor p75 (p75(NTR)), with only a small fraction corresponding to trkC.