Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior in females but not males and protection from neurological deficits during proestrus

Background

Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is one of the most prevalent neurological disorders in the industrialized world. This disease afflicts more than two million people worldwide, over two thirds of which are women. MS is typically diagnosed between the ages of 20–40 and can produce debilitating neurological impairments including muscle spasticity, muscle paralysis, and chronic pain. Despite the large sex disparity in MS prevalence, clinical and basic research investigations of how sex and estrous cycle impact development, duration, and severity of neurological impairments and pain symptoms are limited. To help address these questions, we evaluated behavioral signs of sensory and motor functions in one of the most widely characterized animal models of MS, the experimental autoimmune encephalomyelitis (EAE) model.

Methods

C57BL/6 male and female mice received flank injection of complete Freund’s adjuvant (CFA) or CFA plus myelin oligodendrocyte glycoprotein 35-55 (MOG_35-55) to induce EAE. Experiment 1 evaluated sex differences of EAE-induced neurological motor deficits and neuropathic pain-like behavior over 3 weeks, while experiment 2 evaluated the effect of estrous phase in female mice on the same behavioral measures for 3 months. EAE-induced neurological motor deficits including gait analysis and forelimb grip strength were assessed. Neuropathic pain-like behaviors evaluated included sensitivity to mechanical, cold, and heat stimulations. Estrous cycle was determined daily via vaginal lavage.

Results

MOG_35-55-induced EAE produced neurological impairments (i.e., motor dysfunction) including mild paralysis and decreases in grip strength in both females and males. MOG_35-55 produced behavioral signs of neuropathic pain—mechanical and cold hypersensitivity—in females, but not males. MOG_35-55 did not change cutaneous heat sensitivity in either sex. Administration of CFA or CFA?+?MOG_35-55 prolonged the time spent in diestrus for 2 weeks, after which normal cycling returned. MOG_35-55 produced fewer neurological motor deficits when mice were in proestrus relative to non-proestrus phases.

Conclusions

We conclude that female mice are superior to males for the study of neuropathic pain-like behaviors associated with MOG_35-55-induced EAE. Further, proestrus may be protective against EAE-induced neurological deficits, thus necessitating further investigation into the impact that estrous cycle exerts on MS symptoms.

     

Structures of the tumor necrosis factor α inducing protein Tipα: A novel virulence factor from Helicobacter pylori

Helicobacter pylori secretes a unique virulence factor, Tipα, that enters gastric cells and both stimulates the production of the TNF-α and activates the NF-κB pathway. The structures of a truncated version of Tipα (TipαN34) in two crystal forms are presented here. Tipα adopts a novel β₁α₁α₂β₂β₃α₃α₄ topology that can be described as a combination of three domains. A first region consists in a short flexible extension, a second displays a dodecin-like fold and a third is a helical bundle domain similar to the sterile alpha motif (SAM). Analysis of the oligomerisation states of TipαN34 in the crystals and in solution suggests that the disulfide bridges could hold together Tipα monomers during their secretion in the gastric environment.

Structured summary

MINT-7033680:TIP alpha (uniprotkb:B2UTN0) and TIP alpha (uniprotkb:B2UTN0) bind (MI:0407) by cosedimentation (MI:0027)     

Expression of carboxylesterase and lipase genes in rat liver cell-types

Approximately 80% of the body vitamin A is stored in liver stellate cells with in the lipid droplets as retinyl esters. In low vitamin A status or after liver injury, stellate cells are depleted of the stored retinyl esters by their hydrolysis to retinol. However, the identity of retinyl ester hydrolase(s) expressed in stellate cells is unknown. The expression of carboxylesterase and lipase genes in purified liver cell-types was investigated by real-time PCR. We found that six carboxylesterase and hepatic lipase genes were expressed in hepatocytes. Adipose triglyceride lipase was expressed in Kupffer cells, stellate cells and endothelial cells. Lipoprotein lipase expression was detected in Kupffer cells and stellate cells. As a function of stellate cell activation, expression of adipose triglyceride lipase decreased by twofold and lipoprotein lipase increased by 32-fold suggesting that it may play a role in retinol ester hydrolysis during stellate cell activation.     

Plant physiology in theory and practice: An analysis of the WBE model for vascular plants

The theoretical model of West, Brown and Enquist (hereafter WBE) proposed the fractal geometry of the transport system as the origin of the allometric scaling laws observed in nature. The WBE model has either been criticized for some restrictive and biologically unrealistic constraints or its reliability debated on the evidence of empirical tests. In this work, we revised the structure of the WBE model for vascular plants, highlighting some critical assumptions and simplifications and discuss them with regard to empirical evidence from plant anatomy and physiology. We conclude that the WBE model had the distinct merit of shedding light on some important features such as conduit tapering. Nonetheless, it is over-simplistic and a revised model would be desirable with an ontogenetic perspective that takes some important phenomena into account, such as the transformation of the inner sapwood into heartwood and the effect of hydraulic constraints in limiting the growth in height.     

Su alcune hansenule della fermentazione panaria

Zusammenfassung Es werden zwei neue Arten der Gattung Hansenula, H. panis und H. nivea, beschrieben, die der Verfasser aus Sauerteig (Hefe) gezüchtet hat, wie er zum Brotbacken im Haushalt verwendet wird. In solchem Sauerteig werden Hansenula-Formen zahlreich gefunden.     

Nuovi blastomiceti isolati da mosti del chianti e zone limitrofe

Zusammenfassung Beim Identifizieren von 531 Hefekulturen, die im Herbst 1936 aus Traubenmost des klassischen Chiantigebietes und seiner Umgebung isoliert wurden, fand der Autor folgende neue Arten und Varietäten: Sacch. italicus repräsentiert, soweit heute bekannt, die einzige Spezies der dritten Gruppe nach der Hansen schen Klassifikation der Gattung Saccharomyces. Sacch. ellipsoideus var. major unterscheidet sich von Sacch. ellipsoideus-Typ durch die konstant größeren Zellen und Sporen. Sacch. oviformis var. bisporus zeigt zum Unterschied vom Sacch. oviformis-Typ, außer anderen leichten Abweichungen, Asken mit fast immer zwei, aber nie mehr als zwei Sporen. Zygosaccharomyces florentinus ist ein gutes Beispiel für Übergänge zwischen den Gattungen Torulaspora und Zygosaccharomyces, da sich die seltenen Asken hauptsächlich parthenogenetisch bilden und nur selten das Ergebnis einer Kopulation sind. Zygopichia chiantigiana ermangelt der Fähigkeit zur Alkoholgärung und hat bei der Weinbereitung keine Bedeutung.