GSK-3 and the neurodevelopmental hypothesis of schizophrenia.

The Neurodevelopmental Hypothesis of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances offer insights into the regulation of brain development. The Wnt family of genes plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3beta (GSK-3beta), accumulation and activation of beta-catenin and expression of genes involved in neuronal development. Alteration in the Wnt transduction cascade, which may represent an aberrant neurodevelopment in schizophrenia, is discussed. Programmed cell death is also an essential component of normal brain development. Abnormal neuronal distribution found in schizophrenic patients' brains may imply aberrant programmed cell death. GSK-3 participates in the signal transduction cascade of apoptosis. The possible role of aberrant GSK-3 in the etiology of schizophrenia is discussed.     

Protein synthesis inhibition before or after stress exposure results in divergent endocrine and BDNF responses disassociated from behavioral responses

This study aimed to assess the effects of anisomycin, a protein synthesis inhibitor, on behavioral responses, brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels, and circulating corticosterone in rats-when administered before or after initial exposure to a predator scent stress stimulus. Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and exaggerated startle reaction as well as corticosterone levels and mRNA BDNF and TrkB were compared in rats exposed to predator stress, microinjected with anisomycin before or after stress exposure. Administration of anisomycin before or after stress exposure reduced anxiety-like behavior in the elevated plus-maze and reduced the mean startle amplitude 7 days postexposure. Although the behavioral responses were similar when anisomycin was microinjected before or after stress exposure, the levels of mRNAs for BDNF and TrkB, which play a role in modulation of synaptic plasticity and the consolidation process, showed varying responses.     

The influence of inflammation on the polarization colors of collagen fibers in the wall of odontogenic keratocyst

Epithelial-mesenchymal interactions have been found to play a role in the pathogenesis of odontogenic keratocyst (OKC). In the present study we investigated the effect of inflammation in the OKC wall on the polarization colors of Picrosirius red-stained collagen fibers. 50 cases of OKC were selected and separated into two groups according to the inflammatory intensity: those with mild-to-moderate inflammation (Group A), and those with intense inflammation (Group B). The polarization colors of the collagen fibers were recorded separately for thick and thin fibers. Polarization colors of the thin fibers were in the green- to yellow spectrum, without significant differences between the groups. However, polarization colors of the thick fibers significantly differ between the groups. In Group B, the frequency of thick fibers with green birefringence decreased significantly, whereas fibers with red polarization colors increased in frequency (4.6% and 44%, respectively) compared with Group A (12.3% and 23.6%, respectively). It can than be concluded that inflammation has an impact on the packing of collagen fibers in the connective tissue wall of OKC as reflected by their birefringence colors under polarized light. In the presence of dense inflammation, the percentage of thick fibers with green birefringence decreases, with an increase in thick fibers with red birefringence which appeared more packed.     

Synthesis and metabolism of roquefortine in Penicillium species

The uptake of exogeneous 14C-roquefortine by Penicillium farinosum cells and its metabolism was followed. Growth and roquefortine biosynthesis of three Penicillium species during a cultivation period of 14 d were investigated. Furthermore, the effect of cultivation conditions viz. various culture media on roquefortine uptake and biosynthesis as well as biomass production were studied. Some general problems of physiology and metabolic regulation of alkaloid formation in Penicillium species were discussed.     

Blunted HPA axis response to stress influences susceptibility to posttraumatic stress response in rats.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with low levels of circulating cortisol, and recent studies suggest that cortisol administration may reduce PTSD symptoms. This study investigated the role of cortisol in the manifestation of anxiety- and fear-like symptoms in an animal model of PTSD. METHOD: Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and nonhabituated exaggerated startle reaction were compared in three strains of rats exposed to predator stress, with and without prior corticosterone treatment. Extreme behavioral changes in both paradigms implied an extreme behavioral response (EBR), representing PTSD-like symptoms. RESULTS: Lewis rats exhibited greater baseline anxiety-like behaviors and greater stress-induced increases in anxiety-like behaviors than Fischer F344 or Sprague-Dawley rats, with only minor corticosterone increases following stress. Prevalence of EBR was 50% among Lewis rats compared with 10% of Fischer F344 and 25% of Sprague-Dawley rats. Administering corticosterone 1 hour before stress exposure reduced the prevalence of EBR from 50% to 8% in the Lewis rats. CONCLUSIONS: These results suggest that a blunted HPA response to stress may play a causal role in this model of PTSD and that this susceptibility may be prevented by administration of cortisol before stress exposure.