Serum albumin exposure enhances cell invasiveness and paclitaxel resistance in human neuroblastoma cells, with attenuation by valeriana-type iridoid glycosides.

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFß and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.

A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum.

Genetic variations resulting in the loss of function of the discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated in the increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we have reported that mice lacking exon 14 of the Dlg2 gene (Dlg2 -/- mice) display autistic-like behaviors, including social deficits and increased repetitive behaviors, as well as suppressed spontaneous excitatory postsynaptic currents in the striatum. However, the neural substrate underpinning such aberrant synaptic network activity remains unclear. Here, we found that the corticostriatal synaptic transmission was significantly impaired in Dlg2 -/- mice, which did not seem attributed to defects in presynaptic releases of cortical neurons, but to the reduced number of functional synapses in the striatum, as manifested in the suppressed frequency of miniature excitatory postsynaptic currents in spiny projection neurons (SPNs). Using transmission electron microscopy, we found that both the density of postsynaptic densities and the fraction of perforated synapses were significantly decreased in the Dlg2 -/- dorsolateral striatum. The density of dendritic spines was significantly reduced in striatal SPNs, but notably, not in the cortical pyramidal neurons of Dlg2 -/- mice. Furthermore, a DLG2/PSD-93 deficiency resulted in the compensatory increases of DLG4/PSD-95 and decreases in the expression of TrkA in the striatum, but not particularly in the cortex. These results suggest that striatal dysfunction might play a role in the pathology of psychiatric disorders that are associated with a disruption of the Dlg2 gene.