Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation

Neurotrophin-4 (NT-4) is perhaps the still most enigmatic member of the neurotrophin family. We show here that NT-4 is expressed in neurons of paravertebral and prevertebral sympathetic ganglia, i.e., the superior cervical (SCG), stellate (SG), and celiac (CG) ganglion. Mice deficient for NT-4 showed a significant reduction (20-30%) of preganglionic sympathetic neurons in the intermediolateral column (IML) of the thoracic spinal cord. In contrast, neuron numbers in the SCG, SG, and CG were unchanged. Numbers of axons in the thoracic sympathetic trunk (TST) connecting the SG with lower paravertebral ganglia were also reduced, whereas axon numbers in the cervical sympathetic trunk (CST) were unaltered. Axon losses in the TST were paralleled by losses of synaptic terminals on SG neurons visualized by electron microscopy. Furthermore, immunoreactivity for the synaptic vesicle antigen SV2 was clearly reduced in the SG and CG. Levels of catecholamines and tyrosine hydroxylase immunoreactivity were dramatically reduced in the SG and the CG but not in the SCG. Despite this severe phenotype in the sympathetic system, blood pressure levels were not reduced and displayed a pattern more typical of deficits in baroreceptor afferents. Numbers of IML neurons were unaltered at postnatal day 4, suggesting a postnatal requirement for their maintenance. In light of these and previous data, we hypothesize that NT-4 provided by postganglionic sympathetic neurons is required for establishing and/or maintaining synapses of IML neurons on postganglionic cells. Impairment of synaptic connectivity may consequently reduce impulse flow, causing a reduction in transmitter synthesis in postganglionic neurons

Regulation of GDF-15, a distant TGF-β superfamily member, in a mouse model of cerebral ischemia

GDF-15 is a novel distant member of the TGF-β superfamily and is widely distributed in the brain and peripheral nervous system. We have previously reported that GDF-15 is a potent neurotrophic factor for lesioned dopaminergic neurons in the substantia nigra, and that GDF-15-deficient mice show progressive postnatal losses of motor and sensory neurons. We have now investigated the regulation of GDF-15 mRNA and immunoreactivity in the murine hippocampal formation and selected cortical areas following an ischemic lesion by occlusion of the middle cerebral artery (MCAO). MCAO prominently upregulates GDF-15 mRNA in the hippocampus and parietal cortex at 3 h and 24 h after lesion. GDF-15 immunoreactivity, which is hardly detectable in the unlesioned brain, is drastically upregulated in neurons identified by double-staining with NeuN. NeuN staining reveals that most, if not all, neurons in the granular layer of the dentate gyrus and pyramidal layers of the cornu ammonis become GDF-15-immunoreactive. Moderate induction of GDF-15 immunoreactivity has been observed in a small number of microglial cells identified by labeling with tomato lectin, whereas astroglial cells remain GDF-15-negative after MCAO. Comparative analysis of the size of the infarcted area after MCAO in GDF-15 wild-type and knockout mice has failed to reveal significant differences. Together, our data substantiate the notion that GDF-15 is prominently upregulated in the lesioned brain and might be involved in orchestrating post-lesional responses other than the trophic support of neurons

Personality dimensions of people who suffer from visual stress

Personality dimensions of participants who suffer from visual stress were compared with those of normal participants using the Eysenck Personality Inventory. Extraversion-Introversion scores showed no significant differences between the participants who suffered visual stress and those who were classified as normal. By contrast, significant differences were found between the normal participants and those with visual stress in respect of Neuroticism-Stability. These differences accord with Eysenck's personality theory which states that those who score highly on the neuroticism scale do so because they have a neurological system with a low threshold such that their neurological system is easily activated by external stimuli. The findings also relate directly to the theory of visual stress proposed by Wilkins which postulates that visual stress results from an excess of neural activity. The data may indicate that the excess activity is likely to be localised at particular neurological regions or neural processes

Growth Differentiation Factor 15 Is Induced by Hepatitis C Virus Infection and Regulates Hepatocellular Carcinoma-Related Genes

Liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are commonly induced by chronic hepatitis C virus (HCV) infection. We aimed to identify and characterize the involvement of previously screened cytokine GDF15 in HCV pathogenesis. We examined the GDF15 expression after HCV infection both in vitro and in vivo. Cultured JFH-1 HCV was used to determine the GDF15 function on virus propagation. GDF15 overexpression and RNA interference were employed to profile the GDF15-regulated genes, signaling pathways and cell biology phenotypes. The mRNA expression and protein secretion of GDF15 was dramatically increased in HCV-infected hepatoma cells, which maybe a host response to viral proteins or infection-induced cell stress. Patients infected with HCV had an average 15-fold higher blood GDF15 level than that of healthy volunteers. Three HCC individuals in the HCV cohort showed extremely high GDF15 concentrations. Transfection or exogenously supplied GDF15 enhanced HCV propagation, whereas knockdown of endogenous GDF15 resulted in inhibition of virus replication. Overexpressed GDF15 led to Akt activation and the phosphorylation of Akt downstream targeted GSK-3β and Raf. Several HCC-related molecules, such as E-cadherin, β-catenin, Cyclin A2/B1/D1, were up-regulated by GDF15 stimulation in vitro. Overexpression of GDF15 in hepatoma cells resulted in increased DNA synthesis, promoted cell proliferation, and importantly enhanced invasiveness of the cells. In conclusion, these results suggest that an elevated serum GDF15 level is a potential diagnostic marker for viral hepatitis, and GDF15 may contribute to HCV pathogenesis by altering the signaling and growth of host cells

The Strelau Temperament Inventory - Revised (STI-R): validity studies

Ruch W, Angleitner A, Strelau J. The Strelau Temperament Inventory - Revised (STI-R): validity studies. European journal of personality. 1991;5(4):287-308

The Strelau Temperament Inventory-Revised (STI-R): Theoretical considerations and scale development

he development of a revised Strelau Temperament Inventory (STI-R) is reported. It is assumed that the STI-R provides a measure of the basic central nervous system (CNS) properties (strength of excitation, strength of inhibition, and mobility of the CNS) as understood by Pavlov. On the basis of a series of studies, the development of the final forms of the revised STI has undergone several steps. The following forms have been elaborated: (1) a 252-item pilot form of the STI-R; (2) a 166-item STI-R with ‘yes’ and ‘no’ answer format; (3) a short form (84 items) of the STI-R (STI-RS) with ‘yes’ and ‘no’ answer format; (4) a 166-item STI-R with a 4-point Likert scale; and (5) an 84-item STI-RS with a 4-point rating scale. The psychometric characteristics of the consecutive versions of the revised STI improved from step to step, and in general these characteristics are judged as being satisfactory. Especially recommended by the authors are versions (4) and (5), which have, among other things, the highest reliability scores. They are regarded as the final forms of the STI-R and STI-RS