Involvement of PrPC in kainate-induced excitotoxicity in several mouse strains
نویسندگان
چکیده
The cellular prion protein (PrP(C)) has been associated with a plethora of cellular functions ranging from cell cycle to neuroprotection. Mice lacking PrP(C) show an increased susceptibility to epileptic seizures; the protein, then, is neuroprotective. However, lack of experimental reproducibility has led to considering the possibility that other factors besides PrP(C) deletion, such as the genetic background of mice or the presence of so-called "Prnp flanking genes", might contribute to the reported susceptibility. Here, we performed a comparative analysis of seizure-susceptibility using characterized Prnp(+/+) and Prnp(0/0) mice of B6129, B6.129, 129/Ola or FVB/N genetic backgrounds. Our study indicates that PrP(C) plays a role in neuroprotection in KA-treated cells and mice. For this function, PrP(C) should contain the aa32-93 region and needs to be linked to the membrane. In addition, some unidentified "Prnp-flanking genes" play a role parallel to PrP(C) in the KA-mediated responses in B6129 and B6.129 Prnp(0/0) mice.
منابع مشابه
Neuroprotective and Anti-Inflammatory Roles of the Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy
Excitotoxic damage represents the major mechanism leading to cell death in many human neurodegenerative diseases such as ischemia, trauma and epilepsy. Caused by an excess of glutamate that acts on metabotropic and ionotropic excitatory receptors, excitotoxicity activates several death signaling pathways leading to an extensive neuronal loss and a consequent strong activation of astrogliosis. C...
متن کاملIonotropic Glutamate Receptors and their Role in Neurological Diseases
Glutamate is extensively and relatively uniformly distributed in the central nervous system (CNS) and its effects mediated by two distinct groups of receptors including Ionotropic and metabotropic glutamate receptors. Concentration of glutamate in the nervous system is much higher than in other tissues. Glutamate receptors play an important role in synaptic transmission, neural plasticity and n...
متن کاملO 3:Therapeutic Potential of a Novel NMDA Receptor Subunit 2B Antagonist in a Mouse Model of Autoimmune Neuroinflammation
Glutamate-mediated excitotoxicity and neurodegeneration have been shown as pathophysiological hallmarks of multiple sclerosis (MS) and other autoimmune inflammatory CNS disorders. N‑Methyl‑D‑Aspartate (NMDA) receptors play a pivotal role in the mediation of neuronal glutamate excitotoxicity leading to cellular damage and apoptotic cell death. Current treatment approaches targeting glutamate exc...
متن کاملExcitotoxicity-associated p53 expression in adult rat retina is mediated by calpain activity but not by Cl- influx.
We have previously demonstrated an important role of influx of Cl(-) rather than Ca(2+) in acute excitotoxicity in adult rat retina. As p53 has been implicated in delayed apoptotic cell death, here we examined the appearance of p53 immunoreactivity in a rat eyecup preparation. Kainate induced p53 expression in a subpopulation of ganglion cells and other cells in the ganglion cell layer. Applica...
متن کاملGenetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.
Recent studies have sought to identify the genes involved in excitotoxic neurodegeneration. Here we report that certain strains of mice, including strains that are used for gene targeting studies, do not exhibit excitotoxic cell death after kainic acid seizures. Kainic acid produced excitotoxic cell death in the CA3 and CA1 subfields of the hippocampus in 129/SvEMS and FVB/N mice, in the same p...
متن کامل