Head and neck cancer (HNC) is the sixth most common human malignancy with a global incidence of 650,000 cases per year. Radiotherapy (RT) is commonly used as an effective therapy to treat tumours as a definitive or adjuvant treatment. Despite the substantial advances in RT contouring and dosage delivery, patients suffer from various radiation-induced complications, among which are toxicities to the nervous tissues in the head and neck area. Radiation-mediated neuropathies manifest as a result of increased oxidative stress-mediated apoptosis, neuroinflammation and altered cellular function in the nervous tissues. Eventually, molecular damage results in the formation of fibrotic tissues leading to susceptible loss of function of numerous neuronal substructures. Neuropathic sequelae following irradiation in the head and neck area include sensorineural hearing loss, alterations in taste and smell functions along with brachial plexopathy, and cranial nerves palsies. Numerous management options are available to relieve radiation-associated neurotoxicities notwithstanding treatment alternatives that remain restricted with limited benefits. In the scope of this review, we discuss the use of variable management and therapeutic modalities to palliate common radiation-induced neuropathies in head and neck cancers.
The intracellular molecular pathways involved in radiation‐induced nephropathy are still poorly understood. Glomerular endothelial cells are key components of the structure and function of the glomerular filtration barrier but little is known about the mechanisms implicated in their injury and repair. The current study establishes the response of immortalized human glomerular endothelial cells (GEnC) to ionizing radiation (IR). We investigated the role of sphingolipids and the lipid‐modifying enzyme sphingomyelin phosphodiesterase acid‐like 3b (SMPDL3b) in radiation‐induced GEnC damage. After delivering a single dose of radiation, long and very‐long‐chain ceramide species, and the expression levels of SMPDL3b were elevated. In contrast, levels of ceramide‐1‐phosphate (C1P) dropped in a time‐dependent manner although mRNA and protein levels of ceramide kinase (CERK) remained stable. Treatment with C1P or knocking down SMPDL3b partially restored cell survival and conferred radioprotection. We also report a novel role for the NADPH oxidase enzymes (NOXs), namely NOX1, and NOX‐derived reactive oxygen species (ROS) in radiation‐induced GEnC damage. Subjecting cultured endothelial cells to radiation was associated with increased NOX activity and superoxide anion generation. Silencing NOX1 using NOX1‐specific siRNA mitigated radiation‐induced oxidative stress and cellular injury. In addition, we report a novel connection between NOX and SMPDL3b. Treatment with the NOX inhibitor, GKT, decreased radiation‐induced cellular injury and restored SMPDL3b basal levels of expression. Our findings indicate the importance of SMPDL3b as a potential therapeutic target in radiation‐induced kidney damage.
Although once considered as structural components of eukaryotic biological membranes, research in the past few decades hints at a major role of bioactive sphingolipids in mediating an array of physiological processes including cell survival, proliferation, inflammation, senescence, and death. A large body of evidence points to a fundamental role for the sphingolipid metabolic pathway in modulating the DNA damage response (DDR). The interplay between these two elements of cell signaling determines cell fate when cells are exposed to metabolic stress or ionizing radiation among other genotoxic agents. In this review, we aim to dissect the mediators of the DDR and how these interact with the different sphingolipid metabolites to mount various cellular responses.
Impulsivity is a psychiatric symptom that seems to be more prevalent in some mental disorders such as bipolar disorders (BDs). It is a trait that seems to be influenced by many clinical and sociodemographic variables across BD. To examine the relationship between impulsivity and these variables, we performed a cross-sectional study on 50 patients diagnosed with BD and 50 healthy subjects. Both groups were administered the Barratt Impulsiveness Scale; the Structural Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, for borderline personality disorder; the Beirut District Scale; and the Athens Insomnia Scale to assess impulsivity, borderline personality disorder, psychological distress, and sleep disturbances, respectively. A significantly higher nonplanning impulsivity (p = 0.001), motor impulsivity (p < 0.0001), total impulsivity (p < 0.0001), body mass index (p < 0.0001), and insomnia (p = 0.002) were found in subjects with BDs compared with healthy ones. Exposure to violence (odds ratio [OR] = 7.63), the loss of a parent (OR = 3.83), being a current smoker (OR = 14.56), and a higher motor impulsivity score (OR = 1.27) were all significantly associated with the presence of BD. Impulsivity was shown to be strongly associated with the presence of a diagnosis of BD, and further studies are warranted to fully characterize it through the course of the illness.
Cajal-Retzius cells (CRs) are transient neurons, disappearing almost completely in the postnatal neocortex by programmed cell death (PCD), with a percentage surviving up to adulthood in the hippocampus. Here, we evaluate CR’s role in the establishment of adult neuronal and cognitive function using a mouse model preventing Bax-dependent PCD. CRs abnormal survival resulted in impairment of hippocampus-dependent memory, associated in vivo with attenuated theta oscillations and enhanced gamma activity in the dorsal CA1. At the cellular level, we observed transient changes in the number of NPY+ cells and altered CA1 pyramidal cell spine density. At the synaptic level, these changes translated into enhanced inhibitory currents in hippocampal pyramidal cells. Finally, adult mutants displayed an increased susceptibility to lethal tonic-clonic seizures in a kainate model of epilepsy. Our data reveal that aberrant survival of a small proportion of postnatal hippocampal CRs results in cognitive deficits and epilepsy-prone phenotypes in adulthood.
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