Neurochemical and behavioral alterations in an inflammatory model of depression: Sex differences exposed

It is firmly established that women experience major depression (MD) at roughly twice the rate of men and that dysregulation of the immune system is associated with the appearance and course of this condition. In the present study, we sought to identify whether "sickness behavior", an inflammatory model of MD, is characterized by sexual dimorphism by focusing on both neurochemical and behavioral responses. Therefore, we investigated the serotonergic and dopaminergic activity of various brain regions implicated in the pathophysiology of affective disorders (hypothalamus, hippocampus, prefrontal cortex, amygdala and striatum) in response to a mild lipopolysaccharide (LPS) challenge, in rats of both sexes. According to our results, at 2 h post-LPS administration (100 μg/kg i.p.), the neurochemical substrate was primarily altered in female rats with the serotonergic function being markedly enhanced in all brain regions examined. Dopaminergic activation following immune system sensitization with LPS was not apparent in male rats and only modest in female rats with the exception of striatum. LPS administration also affected sickness-associated behaviors to a different extent in male and female rats, as assessed in the forced swim test (FST), the hot plate test (HPT) and the open-field arena. LPS-treated female rats coped better with the stressful FST procedure, as evidenced by an increase in swimming duration. The effects of LPS treatment appeared to be more robust in male rats, as far as suppression of locomotor activity is concerned, while the antinociceptive properties of LPS were evident in both sexes though showing sex-dependent kinetics. Moreover, when traditional measures of sickness (i.e. sucrose consumption, social exploration, food intake) were assessed, males and females appeared to be similarly affected, except for food intake. These data are the first to demonstrate that the serotonergic system is affected to a greater extent in female rats at 2 h post-LPS administration and further contribute to our understanding regarding sexual dimorphism upon sickness establishment. © 2009 IBRO

Adapting Biodegradable Oligo(Poly(Ethylene Glycol) Fumarate) Hydrogels for Pigment Epithelial Cell Encapsulation and Lens Regeneration

This study investigated the encapsulation of newt iris pigment epithelial cells (PECs), which have the ability to regenerate a lens by trans-differentiation in vivo, within a biodegradable hydrogel of oligo(poly(ethylene glycol) fumarate) crosslinked with poly(ethylene glycol)-diacrylate. Hydrogel beads of initial diameter of 1 mm were fabricated by a molding technique. The swelling ratio and degradation rate of the hydrogel beads decreased with increasing crosslinking ratios. Confocal microscopy confirmed the cytocompatibility of crosslinking hydrogel formulations as evidenced by the viability of an encapsulated model cell line within a crosslinked hydrogel bead. Hydrogel beads encapsulating iris PECs were also implanted into lentectomized newts in vivo; histological evaluation of explants after 30 days revealed a regenerated lens, thus demonstrating that the presence of degrading hydrogel did not adversely affect lens regeneration. The results of this study suggest the potential of a method for lens regeneration involving oligo(poly(ethylene glycol) fumarate) hydrogels for iris PEC encapsulation and transplantation

Forced swim test induces divergent global transcriptomic alterations in the hippocampus of high versus low novelty-seeker rats

Background: Many neuropsychiatric disorders, including stress-related mood disorders, are complex multi-parametric syndromes. Susceptibility to stress and depression is individually different. The best animal model of individual differences that can be used to study the neurobiology of affect regards spontaneous reactions to novelty. Experimentally, when naive rats are exposed to the stress of a novel environment, they display a highly variable exploratory activity and are classified as high or low responders (HR or LR, respectively). Importantly, HR and LR rats do not seem to exhibit a substantial differentiation in relation to their 'depressive-like' status in the forced swim test (FST), a widely used animal model of 'behavioral despair'. In the present study, we investigated whether FST exposure would be accompanied by phenotype-dependent differences in hippocampal gene expression in HR and LR rats. Results: HR and LR rats present a distinct behavioral pattern in the pre-test session but develop comparable depressive-like status in the second FST session. At 24 h following the second FST session, HR and LR rats (stressed and unstressed controls) were sacrificed and hippocampal samples were independently analyzed on whole rat genome Illumina arrays. Functional analysis into pathways and networks was performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal gene expression signatures between HR and LR rats were markedly divergent, despite their comparable depressive-like status in the FST. These molecular differences are reflected in both the extent of transcriptional remodeling (number of significantly changed genes) and the types of molecular pathways affected following FST exposure. A markedly higher number of genes (i.e., 2.28-fold) were statistically significantly changed following FST in LR rats, as compared to their HR counterparts. Notably, genes associated with neurogenesis and synaptic plasticity were induced in the hippocampus of LR rats in response to FST, whereas in HR rats, FST induced pathways directly or indirectly associated with induction of apoptotic mechanisms. Conclusions: The markedly divergent gene expression signatures exposed herein support the notion that the hippocampus of HR and LR rats undergoes distinct transcriptional remodeling in response to the same stress regimen, thus yielding a different FST-related 'endophenotype', despite the seemingly similar depressive-like phenotype. © 2014 Pitychoutis et al.; licensee BioMed Central Ltd

Bone Growth on Reticulated Vitreous Carbon Foam Scaffolds and Implementation of Cellular Automata Modeling as a Predictive Tool

There is a lack of biomaterials that may be used to repair defects in bone. Reticulated Vitreous Carbon (RVC) foam use for medical applications has not been realized. Heat treatment of materials has been shown to enhance material structure and porosity is critical to tissue integration. Three types of RVC foams, 10 pores per inch (ppi), 45-ppi and 100-ppi), were heat-treated to 1800°C. Samples were subjected to compression tests and long-term human osteoblast growth. A three dimensional Cellular Automata model was developed to simulate osteoblast growth. Results from characterization revealed that the compressive strength of foam increased more than 300% as pore size decreased from 1.25 mm to 0.400 mm. Conversely, heat-treated foams exhibited 90% decrease in compressive strength however they displayed 30% increase in osteoblast growth. Additionally, over 28 days, all foam scaffolds exhibited a strong capacity to maintain growth, collagen production and mineralization. Moreover, mineralization on the surface of foams increased the maximum compressive strength by more than 100% for 10-ppi, 65% for 45-ppi and 75% for 100-ppi foam. Cellular Automata modeling correlated to experimental results. This study revealed that scaffolds supported osteoblast growth and mineralization and offered mechanical tunability