A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats

The brain is still maturing during adolescence and interfering with such a vulnerable period may lead to structural and functional consequences. We investigated the effect of a single cocaine exposure on dendritic spine structure and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats 7 days after a single cocaine administration. We found a reduced number of dendritic spines, suggesting that cocaine lowers the density of dendritic spines in the mPFC of adolescent rats. Since dendritic spines are postsynaptic glutamatergic protrusions, we investigated the main determinants of glutamate postsynaptic responsiveness. In the postsynaptic density, cocaine reduced the expression of the NMDA receptor subunits GluN1, GluN2A and GluN2B as well as of the AMPA GluA1 and GluA2 subunits. Cocaine also impaired their synaptic stability since the expression of the scaffolding proteins SAP102 and SAP97, critical for the anchoring of such receptors at the postsynaptic membrane, was reduced as well. The expression of PSD-95 and Arc/Arg3.1, which play structural and functional roles in glutamate neurons, was also similarly reduced. Such changes were not found in the whole homogenate, ruling out a translational effect of cocaine and implying, rather, an impaired synaptic retention at the active zones of the synapse. Notably, neither these critical glutamate determinants nor the density and morphology of the dendritic spines were altered in the mPFC of adult animals, suggesting that a single cocaine exposure selectively impairs the developmental trajectory of the glutamate synapse. These results indicate a dynamic impairment of mPFC glutamate homeostasis during a critical developmental window that persists for at least one week after a single cocaine administration. Our results identify dysfunctional glutamate synapse as a major contributor to the mechanisms that distinguish adolescent vs. adult outcomes of a single cocaine exposure

Insurance Between Firms: The Role of Internal Labor Markets

We investigate how Internal Labor Markets (ILMs) allow organizations to accommodate shocks calling for costly labor adjustments. Using data on workers' mobility within French business groups, we find that adverse shocks affecting affiliated firms boost the proportion of workers redeployed to other group units rather than external firms. This effect is stronger when labor regulations are stricter and destination-firms are more efficient or enjoy better growth opportunities. Affiliated firms hit by positive shocks rely on the ILM for new hires, especially high-skilled workers. Overall, ILMs emerge as a co-insurance mechanism within organizations, providing job stability to employees as a by-product

Development of an LCA-based tool to assess the environmental sustainability level of cosmetics products

The depletion of natural resources and the downgrading of the environment, driven by globalization and consumerism phenomena, are worldwide pushing the interest in sustainable manufacturing paradigm and environment preservation. It is moreover clear to academia and practitioners that the cosmetics industry needs to update its current operations to face new sustainable requirements and norms due to its ever-growing size and massive consumption of natural resources. Different methodologies, metrics, and indicators have been and are being proposed for solving the complex issues of environmental sustainability evaluation of cosmetics processes and products.MethodsAmong these approaches and methods, product-related assessment tools (e.g., life cycle assessment) are usually more focused on the environmental dimension of sustainability, and they are always based on the life cycle of the product. The core of this paper is on the development of a novel tool to classify cosmetics products based on the results of LCA: the eco-friendliness assessment tool (EFAT). The methodology of the work is structured into 5 main phases: definition of the scientific background of the work, definition of the tool requirements, tool development, testing of the tool, analysis of the results. The eco-friendliness assessment tool proposed is structured into two main parts: (i) process flow 1: environmental impact score and (ii) process flow 2: supplier environmental sustainability assessment.ResultsThe tool has been tested on a cosmetics product manufactured in a cosmetics company located in Italy. The acquisition of raw material process and primary packaging process are the two most critical processes resulting from the impact analysis of LCA methodology. The application of the EFAT tool shows the two possible most sustainable improved scenarios are as follows: (i) exploiting transportation of the primary packaging by sea and (ii) adopting the European location of the primary packaging supplier. The results coming from the tool application allowed the definition of the company product eco-friendliness. The eco-friendliness is symbolized by an alphabetical letter and a color.ConclusionsThe paper proposes a practical tool to assess the environmental sustainability level of cosmetics products, with the intention to overcome two of the main literature gaps found in the state of the art: (i) absence of LCA methodology implementation in the cosmetics industry on makeup products, (ii) absence of tools that rely on the results of the LCA analysis of a cosmetic product for understanding its sustainability level of sustainability

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5mM lithium. Although ineffective when used at 0.5mM, lithium at higher concentrations (2mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β)

Repeated cocaine exposure during adolescence impairs recognition memory in early adulthood: A role for BDNF signaling in the perirhinal cortex

The perirhinal cortex (PrhC) is critical for object recognition memory; however, information regarding the molecular mechanisms underlying this type of memory following repeated exposure to drugs of abuse during adolescence is unknown. To this end, adolescent or adult rats were exposed to cocaine from postnatal day (PND) 28 to PND 42 or PND 63 to PND 77, respectively. Two weeks later, rats were subjected to the cognitive test named Novel Object Recognition (NOR) test. We found that adolescent, but not adult, cocaine exposure caused a significant impairment in the NOR test, independently from changes in the stress response system. In adolescent saline-treated rats, NOR test up-regulated BDNF and its downstream signaling whereas a downregulation of the same pathway was observed in cocaine-treated rats together with a reduction of Arc/Arg3.1 and PSD95 expression, indicating reduced pro-cognitive structural adaptations in the PrhC. Of note, cocaine-treated adult rats correctly performed in the NOR test indicating intact recognition memory mechanisms, despite a significant cocaine-induced reduction of BDNF levels in the PrhC, suggesting that recognition memory is heavily dependent on BDNF during adolescence whereas during adulthood other mechanisms come into pla

Autophagy in trimethyltin-induced neurodegeneration

Autophagy is a degradative process playing an important role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria and endoplasmic reticulum, as well as eliminating intracellular pathogens. The autophagic process is important for balancing sources of energy at critical developmental stages and in response to nutrient stress. Recently, autophagy has been involved in the pathophysiology of neurodegenerative diseases although its beneficial (pro-survival) or detrimental (pro-death) role remains controversial. In the present review, we discuss the role of autophagy following intoxication with trimethyltin (TMT), an organotin compound that induces severe hippocampal neurodegeneration associated with astrocyte and microglia activation. TMT is considered a useful tool to study the molecular mechanisms occurring in human neurodegenerative diseases such as Alzheimer’s disease and temporal lobe epilepsy. This is also relevant in the field of environmental safety, since organotin compounds are used as heat stabilizers in polyvinyl chloride polymers, industrial and agricultural biocides, and as industrial chemical catalysts

Enhancing the cosmetics industry sustainability through a renewed sustainable supplier selection model

The cosmetics industry requires a long-term sustainable strategy to balance its continuously growing trend worldwide and its resources consumption. In this view, the suppliers' selection process is gaining more attention affecting products' overall sustainability. The objective of this contribution is hence to develop and validate the Cosmetics Sustainable Supplier Selection (C-SSS) model allowing the selection of sustainable suppliers for the cosmetic industry, evaluating them in an objective and balanced manner. The model was built relying on both scientific and grey literature, by incorporating the characteristics of existing SSS models usually used separately. The C-SSS enabled to integrate the EMM approach (to reduce the subjectivity), the ANP approach (to evaluate criteria interconnections), and the TOPSIS and ELECTRE models (to create a hybrid compensation model) to support managers in objectively selecting the most sustainable suppliers. The C-SSS model was applied and validated through an industrial use case in a cosmetics Italian company