IBEC researchers have revealed the role played by the cellular prion protein (PrP^C) –which is associated with a plethora of biological functions including cell proliferation, differentiation and signaling – in epilepsy. In the latest edition of Scientific Reports (doi:10.1038/srep11971), a Nature group journal, the Molecular and Cellular Neurobiotechnology group and their collaborators outline findings that could lead to a better understanding of rapid neurodegenerative diseases that involve epileptic fits, such as Creutzfeldt-Jacob disease (CJD).

PrP^C – found naturally in healthy brain and decreased in several diseases such us diseases such as bovine spongiform encephalopathy (BSE) and human rapid progressive dementia (RPD) CJD – has long been thought to be neuroprotective, so the IBEC researchers hypothesized that an explanation for seizure symptoms in these neurodegenerative diseases could be associated with the loss of function of PrPC.

“We performed a comparative analysis of seizure susceptibility using mice with six different genetic backgrounds and several in vitro experiments,” says José Antonio del Río, who leads the Molecular and Cellular Neurobiotechnology group at IBEC. “We indeed demonstrated that mice lacking PrP^C showed an increased susceptibility to epileptic episodes leading to cell death in the hippocampal region, supporting the notion that the protein is involved in neuroprotection against seizures, and that it actively participates in the increased epileptic response observed in mice, independently of the genetic background, that lack it.”

Their study, which also involved researchers at the UB, IDIBELL, CIBERNED, CISA-INIA, DZNE in Germany, and SISSA in Italy, also revealed that other factors in parallel with PrPC deletion, such as the genetic background of some of the mice used for PrP^C analysis, or the presence of so-called ‘Prnp-flanking genes’ in the mixed genetic background of PrP^C knockout mice, might contribute to susceptibility to epileptic fits in the absence of PrP^C.

“In the neurodegeneration found in rapid progressive dementia cases of CJD, Alzheimer’s or Dementia with Lewy Bodies, the survival time from clinical diagnosis to death is very short, with tremor and epileptic seizures being a common and clinical feature for some of these dementias,” says del Río. “With our new findings, we’re a step closer to understanding more about the neurodegenerative diseases that involve epileptic seizures, which means a step closer to developing new therapies or diagnostic tools.”