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Tumor necrosis factor-alpha is a central cytokine involved in the regulation of the innate immune response. Signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 are second messengers mediating the Th1 and Th2-specific immune responses, respectively. We studied the outcome of spinal cord injury with respect to the locomotion and axonal regeneration in tumor necrosis factor-alpha, signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 knockout mice. Locomotor behavior after injury differed between mouse strains, but not between wild-type and the knockout genotypes of the same strain. Regeneration of descending tracts, assessed by fluorogold/fluororuby retrograde double-labeling, however, appeared hampered by Th2 deficiency.

The Nogo system has recently been implicated not only in regeneration but also in modulating plasticity. One reason for declining memory functions in aging may be altered plasticity in the aged hippocampus and cortex cerebri. Therefore, we have examined the levels of mRNA encoding Nogo, OMgp and MAG, as well as the receptor components NgR, Lingo-1 and Troy in cortex and hippocampus of young (4 months), middle aged (16 months) and old (24 months) Fisher 344 rats. No significant changes of receptor components or the ligands OMgp or MAG were observed. Nogo mRNA, however, was significantly decreased in hippocampal subregions of aged animals. The specific decrease of Nogo mRNA levels in hippocampus and possibly cortex cerebri may relate to age-dependent decline of brain plasticity.

BACKGROUND Recently, linkage disequilibrium mapping of the major histocompatibility complex region on the short arm of human chromosome 6 suggested that the NOTCH4 locus is highly associated with schizophrenia. OBJECTIVES AND METHODS We analysed two polymorphisms in this gene in Swedish schizophrenic patients ( =74) and control subjects ( =135). The NOTCH4 variants were also analysed in schizophrenic patients with regard to subdiagnosis, age at first hospitalization, abuse/dependence of alcohol, solvents, or drugs, previous suicide attempts, extrapyramidal symptoms, treatment with anticholinergic drugs, and response to anti-psychotic drug treatment. Control subjects were scrutinized with regard to personality, another partially heritable trait suggested being of importance in schizophrenia. In addition, two intermediate endophenotypes suggested being of importance in schizophrenia, dopamine D(2) receptor density in striatum and monoamine metabolites in cerebrospinal fluid, respectively, were investigated with regard to the two NOTCH4 variants. RESULTS There was no significant association between the patients and the controls for the two investigated polymorphisms neither for the parameters analysed in the schizophrenia material. The NOTCH4 SNP2 variant, an A-->G substitution, was associated with the Karolinska Scales of Personality Irritability scale. The NOTCH4 (CTG)(n) variant was associated with the revised NEO personality inventory Extraversion and Activity (E4) scales. However, after correction for multiple testing, no difference remained significant. The results for the endophenotypes and the polymorphisms were non-significant. CONCLUSIONS The present study does not support that the investigated NOTCH4 variants have a major influence on susceptibility to schizophrenia or related neurobiological traits.

Facial nerve lesions lead to a retrograde response characterized by activation of glia surrounding axotomized motoneurons and up-regulation of immunological cell surface molecules such as major histocompatibility complex (MHC) antigens. Cytokines, in particular interferon-gamma, are potent inducers of MHC expression and glial activation. We have here tested whether axotomy-induced activation is changed in transgenic mouse strains lacking components of the IFN-gamma signaling pathway, STAT4 or STAT6. No differences regarding astrocyte activation, ss2-microglobulin or MHC class I expression were discernible as compared to wild type controls. In contrast, there were conspicuous differences in the reaction between the examined wild type strains (C57BL/6J, BALB/c and 129/SvJ), suggesting considerable polymorphisms in the genetic regulation of these events, however, not involving IFN-gamma, STAT4 or STAT6.

Early alterations in mRNAs encoding neurotrophins and stress proteins were investigated following intracerebroventricular injections of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) in adult rats using in situ hybridization. Major increases in heat-shock protein 70, c-fos and brain-derived neurotrophic factor (BDNF) mRNAs were seen in hippocampus 1 h after BOAA or BMAA injections. Nerve growth factor mRNA was profoundly increased in the dentate gyrus (DG) after both treatments. Four hours after BMAA injections increased hybridization to BDNF mRNA was still seen in hippocampus, in parallel with reduced neurotrophin-3 expression in the DG. These alterations are in accordance with previous findings of BOAA and BMAA as potent glutamate receptor agonists.