Communication defects with astroglia contribute to early impairments in the motor cortex plasticity of SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1G93A mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1G93A mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.

Cytotoxic activity of poly-ɛ-caprolactone lipid-core nanocapsules loaded with lycopene-rich extract from red guava (Psidium guajava L.) on breast cancer cells.

The aims of this study were to produce poly-ɛ-caprolactone lipid-core nanocapsules containing lycopene-rich extract from red guava (LEG), to characterize those nanoparticles and to evaluate their cytotoxic effects on human breast cancer cells. Lipid-core nanocapsules containing the extract (nanoLEG) were produced by the method of interfacial deposition of the preformed polymer. The nanoparticles were characterized by Dynamic Light Scattering (DLS), Polydispersity Index, Zeta Potential, pH, Encapsulation Efficiency, Nanoparticle Tracking Analysis (NTA), Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). Cell viability was evaluated by the MTT dye reduction method in the human breast cancer MCF-7 cell line and inhibition of ROS and NF-κB was assayed in living human microglial cell line (HMC3) by time-lapse images microscopy. A hemolytic activity assay was carried out with sheep blood. Data showed that nanoparticles average size was around 200 nm, nanoparticles concentration/mL was around 0.1 µM, negative zeta potential, pH < 5.0 and spherical shape, with low variation during a long storage period (7 months) at 5 °C, indicating stability of the system and protection against lycopene degradation. The percentage of encapsulation varied from 95% to 98%. The nanoLEG particles significantly reduced the viability of the MCF-7 cells after 24 h (61.47%) and 72 h (55.96%) of exposure, even at the lowest concentration tested (6.25-200 µg/ml) and improved on the cytotoxicity of free LEG to MCF-7. NanoLEG inhibited LPS-induced NF-kB activation and ROS production in microglial cells. The particles did not affect the membrane integrity of sheep blood erythrocytes at the concentrations tested (6.25-200 µg/mL). Thus, the formulation of lipid-core nanocapsules with a polysorbate 80-coated poly-ɛ-caprolactone wall was efficiently applied to stabilize the lycopene-rich extract from red guava, generating a product with satisfactory physico-chemical and biological properties for application as health-promoting nanotechnology-based nutraceutical, emphasizing its potential to be used as a cancer treatment.