Genomic profiling of cortical neurons following exposure to β-amyloid

In vitro and in vivo studies have shown that beta-amyloid peptide induces neuronal cell death. To explore the molecular basis underlying beta-amyloid-induced toxicity, we analyzed gene expression profiles of cultured rat cortical neurons treated for 24 and 48 h with synthetic beta-amyloid peptide. From the 8740 genes interrogated by oligonucleotide microarray analysis, 241 genes were found to be differentially expressed and segregated into distinct clusters. Functional clustering based on gene ontologies showed coordinated expression of genes with common biological functions and metabolic pathways. The comparison with genes differentially expressed in cerebellar granule neurons following serum and potassium deprivation indicates the existence of common regulatory mechanisms underlying neuronal cell death. Our results offer a genomic view of the changes that accompany beta-amyloid-induced neurodegeneration

Behavioural and neurochemical changes induced by stress-related conditions are counteracted by the neurokinin-2 receptor antagonist saredutant.

Abstract These experiments were undertaken to assess the mechanisms underlying the antidepressant-like effects of the neurokinin-2 (NK2) receptor antagonist saredutant (SR48968) in rats tested in the forced swim test (FST), by analysing hippocampal brain-derived neurotrophic factor (BDNF) and plasma corticosterone [as index of hypothalamic-pituitary-adrenal (HPA) axis activity]. Male Wistar rats received three intraperitoneal injections over 24 h of vehicle, saredutant (5 mg/kg), citalopram (15 mg/kg), clomipramine (50 mg/kg). Rats were subjected to restraint stress (4 h) 24 h prior to the FST procedure. This stress procedure increased immobility and decreased swimming behaviour in the FST; furthermore, it lowered hippocampal BDNF protein expression and increased plasma corticosterone levels. Saredutant and clomipramine or citalopram, used here as positive controls, reduced the immobility time in the FST both under basal conditions and after stress exposure. This effect was not attributable to changes in locomotion, because locomotor activity was unchanged when assessed in the open field test. Pretreatment with para-cholorophenylalanine (150 mg/kg, 72 h and 48 h prior to FST) abolished the effect of citalopram and saredutant on immobility time. At neurochemical level, saredutant attenuated activation of HPA axis in stressed animals more than clomipramine or citalopram. The behavioural effects of saredutant support the hypothesis that NK2 receptor activity is involved in stress-related disorders. These effects of saredutant may be related to normalization of the HPA axis. Moreover, saredutant increases BDNF expression in the hippocampus, confirming the role of NK2 receptor blockade in BDNF activation following stressor application

Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain

<p>Abstract</p> <p>Background</p> <p>Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36.</p> <p>Results</p> <p>Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP) under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine) and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH), and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36.</p> <p>Conclusion</p> <p>Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.</p

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals

Analysis of cCx39 expression pattern during chick development

The present study reports the expression pattern of connexin39 (cCx39) in chick embryos at different stages of central nervous system development. We examined the expression between HH17 and HH40 developmental stages of chicken embryos by in situ hybridization (ISH) technique. Connexin39 was first expressed at HH17. It stained neuroepithelial cells in the optic (OV) and telencephalic (TEL) vesicles, plus in the superficial mesenchyme of the two rostral branchial arches (maxilar and mandibular). These cells probably originated from the neural crest. This expression pattern changed drastically between stages HH17 and HH23, while it showed relatively little modifications from HH23 to HH29. At these times, connexin39 was expressed in three regions: the telencephalic vesicle, the diencephalon and the isthmus. At later stages, HH35 and HH40, connexin39 was mainly expressed in the ventricular epithelium and three cell layers of the stratum griseum and fibrosum superficialis (SGFS) in the optic tectum, as well as in granular and nuclear cells in the cerebellum. In conclusion, the expression pattern of connexin39 in embryonic nervous system is dynamic. This pattern is different from, and in some aspects complementary to, those showed by other connexins during brain development.Peer reviewe