Distribution and dynamics of cell surface-associated cellCAM 105 in cultured rat hepatocytes

The cellular location of cellCAM 105 was studied by indirect immunofluorescence microscopy of primary rat hepatocytes grown in monolayer culture. Staining corresponding to cellCAM 105 was seen both in cell-cell contact areas and on the upper surfaces of the cells. In the cell-cell contact areas the antigen was not accessible to the antibodies unless the cells were either permeabilized with detergent or incubated in a calcium-free medium. Removal of calcium from the medium caused the cells to separate from each other. Within a few minutes wide intercellular clefts were formed, and upon further incubation the cells became stellate-shaped and finally remained in contact with each other only via thin cellular processes. These processes were cellCAM 105-positive and at sites where they attached to the bodies of the contracted cells a granular fluorescence pattern appeared. After 24-48 h of culture, intercellular channels resembling bile canaliculi were sometimes formed in the hepatocyte monolayers. The membranes of these intercellular channels were stained for cellCAM 105. After culture for several days the hepatocytes lost their polygonal shape and gradually acquired a more fibroblast-like morphology. This morphological change was accompanied by a decrease in cellCAM 105-specific fluorescence, both in the cell-cell contact areas and on the free cell surfaces

Region Specific Hypothalamic Neuronal Activation and Endothelial Cell Proliferation in Response to Electroconvulsive Seizures.

Background: Major depression is often associated with disturbances in basal biological functions regulated by the hypothalamus. Electroconvulsive therapy (ECT), an efficient anti-depressant treatment. alters the activity of hypothalamic neurons. We have previously shown an increased proliferation of endothelial cells in specific areas of the rat hippocampus in response to electroconvulsive seizure (ECS) treatment, an animal model for ECT. Here we examine the effect of ECS treatment on neuronal activation and endothelial cell proliferation in mid-hypothalamus. Methods. Rats received one daily ECS treatment for 5 days and cell proliferation was detected by bromodeoxyuridine (BrdU). The number of cells double-labeled for BrdU and the endothelial cell marker rat endothelial cell antigen-1 was determined. Neuronal activation in response to acute ECS treatment was detected as c-Fos immunoreactivity in an additional experiment. Results: We demonstrate a correlating pattern of increases in neuronal activation and increased endothelial cell proliferation in the paraventricular nucleus, the supraoptic nucleus, and the ventromedial nucleus of the hypothalamus after ECS treatment. Conclusions: Hypothalamic areas with the largest increase in neuronal activation after ECS treatment exhibit increased endothelial cell proliferation. We suggest that similar angiogenic responses to ECT might counteract hypothalamic dysfunction in depressive disorder

Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex.

Stress and environmental enrichment have opposing effects on cerebral cellular plasticity. Stress-induced disturbances in neuronal and glial plasticity have been implicated in the pathophysiology of affective disorders. Patients with depression often show volume reductions in specific brain regions. The mechanisms behind these changes are not well understood, but animal studies have indicated that increased levels of glucocorticoids and stress have negative impact on the neuronal and glial cell populations. On the contrary, enriched environment and physical activity have positive effects. In this study we have examined the effect of corticosterone (CORT), environmental enrichment (EE) and running on angiogenesis in hippocampus and prefrontal cortex (PFC). We demonstrate a dramatic inhibition in endothelial cell proliferation in these brain regions in CORT-treated rats. Environmental enrichment had the opposite effect and stimulated endothelial cell proliferation both in the hippocampus and in the PFC. Running had a stimulatory effect in hippocampus, but not in the PFC. We suggest that the angiostatic effect of CORT demonstrated in this study might be paralleled in human subjects exposed to high levels of stress hormones for prolonged periods of time. Raised cortisol levels in depressed or old patients could, by reducing endothelial cell formation/turnover, lead to rarefaction and aging of the vascular bed, and as a result, neuronal function could be impaired. It is tempting to speculate that a physically and intellectually active life may protect against stress-induced vascular changes. Therapeutic agents also targeting the cerebral vasculature could consequently constitute a new tool in the combat of stress-related disorders

Chronic lithium treatment decreases NG2 cell proliferation in rat dentate hilus, amygdala and corpus callosum

An increasing number of investigations suggest volumetric changes and glial pathology in several brain regions of patients with bipolar disorder. Lithium, used in the treatment of this disorder, has been reported to be neuroprotective and increase brain volume. Here we investigate the effect of lithium on the proliferation and survival of glial cells positive for the chondroitin sulphate proteoglycan NG2 (NG2 cells); a continuously dividing cell type implicated in remyelination and suggested to be involved in regulation of neuronal signaling and axonal outgrowth. Adult male rats were treated with lithium for four weeks and injected with the proliferation marker bromodeoxyuridine (BrdU) before or at the end of the treatment period. Immunohistochemical analysis of brain sections was performed to estimate the number of newly born (BrdU-labeled) NG2 cells and oligodendrocytes in hippocampus, basolateral nuclei of amygdala and corpus callosum. Lithium significantly decreased the proliferation of NG2 cells in dentate hilus of hippocampus, amygdala and corpus callosum, but not in the molecular layer or the cornu ammonis (CA) regions of hippocampus. The effect was more pronounced in the corpus callosum. No effect of lithium on the survival of newborn cells or the number of newly generated oligodendrocytes could be detected. Our results demonstrate that in both white and gray matter brain regions implicated in the pathophysiology of bipolar disorder, chronic lithium treatment significantly decreases the proliferation rate of NG2 cells; the major proliferating cell type of the adult brain. (C) 2009 Elsevier Inc. All rights reserved

Repeated electroconvulsive seizures increase the number of vessel-associated macrophages in rat hippocampus.

OBJECTIVES: We have previously reported that electroconvulsive seizure (ECS)-an animal model of the antidepressant treatment electroconvulsive therapy-causes glial cell activation in hippocampus and other limbic areas. In the current study, we have investigated whether the cellular response to ECS includes recruitment and infiltration of nonresident macrophages into the hippocampal brain parenchyma. METHODS: Adult rats received 1 ECS daily for 10 consecutive days and were then killed at different time points after the last ECS treatment. Brain sections were immunostained for laminin, a matrix protein expressed in the basal membrane of blood vessels, in combination with anti-CD163, which identifies mature blood-borne macrophages. The number of CD163 cells in the hippocampus was quantified. We also investigated the number of vessel-associated cells expressing CD4 and major histocompatibility complex class II (MHC II). CD4 is mainly expressed by CD4 T cells, but can also be found on macrophages, monocytes, and activated microglia, whereas MHC II is expressed by macrophages, activated microglia, dendritic cells, and B cells. RESULTS: Our results demonstrate increased numbers of CD163 and CD4 cells following ECS. Most CD4 cells within the vasculature had a similar morphology to the CD163 macrophages. No CD163 cells were detected outside the vessels but a subpopulation of CD4 cells was seen in the brain parenchyma, here with a morphology resembling microglia. There was a transient increase in the number of blood vessel-associated MHC II cells following ECS. CONCLUSIONS: Our observations showed that the cellular response to ECS involves recruitment of blood-derived macrophages, but we could not see any infiltration into the brain parenchyma of these cells