Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.

The ubiquitin-proteasome system (UPS) plays a fundamental role in protein degradation in neurons, and there is strong evidence that it fulfills a key role in synaptic transmission. The aim of the present work was to study the implication of one component of the UPS, the HERC1 E3 Ubiquitin Ligase, in motor function and neuromuscular transmission. The tambaleante (tbl) mutant mouse carries a spontaneous mutation in HERC1 E3 Ubiquitin Ligase, provoking an ataxic phenotype that develops in the second month of life. Our results show that motor performance in mutant mice is altered at postnatal day 30, before the cerebellar neurodegeneration takes place. This defect is associated with by: (a) a reduction of the motor end-plate area, (b) less efficient neuromuscular activity in vivo, and (c) an impaired evoked neurotransmitter release. Together, these data suggest that the HERC1 E3 Ubiquitin Ligase is fundamental for normal muscle function and that it is essential for neurotransmitter release at the mouse neuromuscular junction.

We propose further studies on mtDNA sequence analysis in patients with FM with evidences for maternal inheritance. The presence of similar symptoms in mitochondrial myopathies could unmask mitochondrial diseases among patients with FM. On the other hand, the inflammasome complex activation by mitochondrial dysfunction could be implicated in the pathophysiology of mitochondrial diseases.

The use of first and second generation antiepileptic drugs during pregnancy doubles the risk of major congenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generation antiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has been associated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test the potential teratogenic effects of LCM on developing embryos and its effects on behavioural/histological alterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and that of related compounds, in the mothers’ serum and in embryonic tissues using liquid chromatography coupled to quadrupole/time of flight mass spectrometry detection. Embryo morphology was evaluated, and immunohistochemistry was performed on adult offspring. Behavioural studies were carried out during the first two postnatal weeks and on adult mice. We found a high incidence of embryonic lethality and malformations in mice exposed to LCM during embryonic development. Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delay and behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdala that were associated with behaviours associated with schizophrenia spectrum disorders in adulthood. We conclude that LCM and its metabolites may have teratogenic effects on the developing embryos, reflected in embryonic lethality and malformations, as well as behavioural and histological alterations in adult mice that resemble those presented by patients with schizophrenia.