Genetic Downregulation of the Metabotropic Glutamate Receptor Type 5 Dampens the Reactive and Neurotoxic Phenotype of Adult ALS Astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs). Astrocytes display a toxic phenotype in ALS, which results in MN damage. Glutamate (Glu)-mediated excitotoxicity and group I metabotropic glutamate receptors (mGluRs) play a pathological role in the disease progression. We previously demonstrated that in vivo genetic ablation or pharmacological modulation of mGluR5 reduced astrocyte activation and MN death, prolonged survival and ameliorated the clinical progression in the SOD1G93A mouse model of ALS. This study aimed to investigate in vitro the effects of mGluR5 downregulation on the reactive spinal cord astrocytes cultured from adult late symptomatic SOD1G93A mice. We observed that mGluR5 downregulation in SOD1G93A astrocytes diminished the cytosolic Ca2+ overload under resting conditions and after mGluR5 simulation and reduced the expression of the reactive glial markers GFAP, S100ß and vimentin. In vitro exposure to an anti-mGluR5 antisense oligonucleotide or to the negative allosteric modulator CTEP also ameliorated the altered reactive astrocyte phenotype. Downregulating mGluR5 in SOD1G93A mice reduced the synthesis and release of the pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α and ameliorated the cellular bioenergetic profile by improving the diminished oxygen consumption and ATP synthesis and by lowering the excessive lactate dehydrogenase activity. Most relevantly, mGluR5 downregulation hampered the neurotoxicity of SOD1G93A astrocytes co-cultured with spinal cord MNs. We conclude that selective reduction in mGluR5 expression in SOD1G93A astrocytes positively modulates the astrocyte reactive phenotype and neurotoxicity towards MNs, further supporting mGluR5 as a promising therapeutic target in ALS.

Passively concerned: Horeca managers' recognition of the importance of food waste hardly leads to the adoption of more strategies to reduce it.

Recent works have found a negative correlation between the amount of food waste generated in foodservice outlets and the extent to which managers perceive it as a relevant problem. However, it is hard to believe that food flows would be impacted by wishful thinking alone. In this paper, we try to offer an explanation to these findings by testing the associations between importance recognition, food waste measurement and compliance to waste reduction strategies in three different stages (pre-kitchen, in-kitchen and post-kitchen). We do so by fitting a generalized structural equation model in the results of a survey ran in Italy with almost 500 Horeca (Hotels, restaurants and cafeterias) managers. Our findings reveal that importance perception triggers strategies' adoption in only one of the three stages (in-kitchen). Furthermore, this association is essentially dependent on the mediation performed by measurement, suggesting that importance recognition covers a complex pathway to arrive in reduced amounts of waste. Additional results indicate that larger and higher-end outlets tend to place more importance on food waste. Moreover, although 77% of the sample recognizes the relevance of food waste to their businesses, the incorporation of some of the main reduction strategies is still low, as 85% of the establishments report the adoption of no more than 3 out of the 9 strategies presented.