Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus

MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in Prader-Willi syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Maged1-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Maged1 also results in a complex behavioral syndrome that includes reduced social interactions and memory, deficient sexual behavior, as well as increased anxiety and self-grooming. Oxytocin (OT), which is produced in the hypothalamus, can act as a neurotransmitter that reduces anxiety, promotes social behaviors and regulates food intake. Growing evidences indicate that OT is involved in autism. We found that Maged1 mutants showed a severe reduction in the levels of mature OT, but not of its precursors, in the hypothalamus. Moreover, the administration of OT rescued the deficit in social memory of these mice. We conclude that Maged1 is required for OT processing or stability. A decrease in mature OT levels in Maged1 mutants affects social interactions and possibly other behavioral processes. Our observations suggest that, in human, MAGED1 could play a role in autism or cause a neurodevelopmental condition that is reminiscent of the PWS

Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord

We hypothesized that VEGF-containing hydrogels that gelify in situ following injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% MVG alginate, supplemented or not with fibrinogen, were used. The addition of fibrinogen to alginate had no effect on cell proliferation in vitro but supported neurite growth ex vivo. When injected into a rat spinal cord in a hemisection model, alginate supplemented with fibrinogen was well tolerated. The release of VEGF that was incorporated into the hydrogel was influenced by the VEGF formulation (encapsulated in microspheres or in nanoparticles or in solution (free)). A combination of free VEGF and VEGF-loaded nanoparticles was mixed with alginate:fibrinogen and injected into the lesion of the spinal cord. Four weeks post-injection injection, angiogenesis and neurite growth were increased compared to hydrogel alone. The local delivery of VEGF by injectable alginate:fibrinogen-based hydrogel induced some plasticity in the injured spinal cord involving fiber growth into the lesion site

Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord

We hypothesized that VEGF-containing hydrogels that gelify in situ following injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% MVG alginate, supplemented or not with fibrinogen, were used. The addition of fibrinogen to alginate had no effect on cell proliferation in vitro but supported neurite growth ex vivo. When injected into a rat spinal cord in a hemisection model, alginate supplemented with fibrinogen was well tolerated. The release of VEGF that was incorporated into the hydrogel was influenced by the VEGF formulation (encapsulated in microspheres or in nanoparticles or in solution (free)). A combination of free VEGF and VEGF-loaded nanoparticles was mixed with alginate:fibrinogen and injected into the lesion of the spinal cord. Four weeks post-injection injection, angiogenesis and neurite growth were increased compared to hydrogel alone. The local delivery of VEGF by injectable alginate:fibrinogen-based hydrogel induced some plasticity in the injured spinal cord involving fiber growth into the lesion site

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low III tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals

GUT MICROBIOTA IS IMPLICATED IN CANCER-INDUCED CACHEXIA

BACKGROUND AND AIMS : We know that the gut microbiota is implicated in energy metabolism and it role has been mostly studied upon obesity . Here we set the hypothesis that the gut microbiota could also be implicated in metabolic alterations associated with cancer, cachexia. METHODS : This hypothesis was assessed in BALB/c mice intravenously injected with mouse proB BAF3 cells transfected with BCR-ABL gene in order to allow the development of chronic myelogenous leukemia (CML). Muscles (tibialis, gastrocnemius), liver, intestine and adipose tissues were withdrawn 2 weeks after injection for further biochemical and histological analysis. Gut microbiota composition was assessed by RT-qPCR. RESULTS : BCR-ABL expressing CML constitutes a new model of cancer cachexia, as proven by a decrease in adipose and muscle tissue weights. In both male and female, Lactobacillus spp. levels in caecal content drastically decrease, independently of food intake (p<0,001). Moreover, this decrease is highly correlated to muscle markers of atrophy, such as Atrogin-1 mRNA (r = -0,8885, p<0,0001). Finally, increasing the level of Lactobacillus spp. levels by dietary prebiotics allows to lessen Atrogin-1 mRNA induction in the muscle. CONCLUSIONS : In this new model of cancer cachexia, we highlight two important facts : first, gut microbiota modification is associated with cancer-induced cachexia ; second, modulation of gut microbiota counteracts markers of muscle atrophy. Therefore, we suggest that gut microbiota is implicated in cancer cachexia and may constitute a new target in the treatment of this metabolic disease