Biology subjects

Piscitelli, F.

Publications and source records attributed to Piscitelli, F..

3 recordsLinked to original sources

bioRxiv2023

Sleep loss impairs myelin function by altering cholesterol metabolism in oligodendroglia

The increasing prevalence of sleep deprivation in modern society demands comprehension of the biological consequences of sleep loss on brain functioning. Our study reveals significant effects of sleep deprivation on myelin integrity. As a result, we identify increased conduction delays in nerve signal propagation, hindered interhemispheric synchronization, and impaired motor performance associated with sleep loss. By profiling oligodendrocyte transcriptome and lipidome, we observe sleep loss-induced endoplasmic reticulum stress and lipid metabolism disruption, particularly affecting cholesterol homeostasis. This shift in cholesterol levels alters myelin physical properties. Boosting cholesterol transport to myelin sheaths prevents sleep loss effects on nerve signal propagation and behavior. Our findings highlight the critical role of oligodendrocyte cholesterol regulation in behavioral deficits associated with sleep loss and unveil a novel target for intervention.

neuroscience↗

bioRxiv2023

Astrocytes modulate neuronal development by S100A6 signaling

Neuronal morphogenesis relies on intercellular signaling. Astrocytes release metabolites, trophic, and guidance factors to promote neuronal maturation. In contrast, the mechanisms by which astrocytes could limit and stabilize neuronal connectivity remain less explored. Here, we show cortical astrocytes to express and release S100A6, a Ca2+-binding protein ( calcyclin). Simultaneously, the majority of cortical neurons express calcyclin-binding protein (CaCyBp), a bona fide binding partner for S100A6. In neurons, CaCyBp maintains the unfolded protein response pathway, thereby controlling proteostasis. When released, S100A6 inhibits CaCyBp-mediated signaling, thus slowing protein turnover, and, consequently, neuritogenesis. S100A6-CaCyBp signaling during gestation and lactation is sensitive to the mothers nutritional status, particularly eicosapentaenoic acid intake. Thus, a member of the S100 protein family acts as an astroglia-derived morphogen, whose action on neurons is modulated by environmental factors.

neuroscience↗

bioRxiv2020

Gene Deletion Studies Reveal A Critical Role For Prostamide/Prostaglandin F2α Synthase In Prostamide F2α Formation

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F2. The importance of this enzyme, relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F2 levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F2 levels in WT and PM/PGFS KO mice were determined by LC/MS/MS. Intraocular pressure was measured by tonometry and outflow facility was measured by the iPerfusion method in enucleated mouse eyes. Deletion of fam213b had no observed effect on behavior, appetite, or fertility. Intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. No effect on pressure dependent outflow facility occurred, which is consistent with the typically reported prostanoid effect of increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids that raise intraocular pressure, namely prostaglandin D2 (PGD2), thromboxane A2 (TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2 and prostamide F2 to constrain the influence of those prostanoids that raise intraocular pressure.

pharmacology and toxicology↗