Ryanodine receptors drive neuronal loss and regulate synaptic proteins during epileptogenesis
EXPERIMENTAL NEUROLOGY
Authors: Royero, Pedro Xavier; Vilar Higa, Guilherme Shigueto; Kostecki, Daiane Soares; dos Santos, Bianca Araujo; Almeida, Cayo; Andrade, Kezia Accioly; Kinjo, Erika Reime; Kihara, Alexandre Hiroaki
Abstract
Status epilepticus (SE) is a clinical emergency that can lead to the development of temporal lobe epilepsy (TLE). The development and maintenance of spontaneous seizures in TLE are linked to calcium (Ca+2 )-dependent processes such as neuronal cell loss and pathological synaptic plasticity. It has been shown that SE produces an increase in ryanodine receptor-dependent intracellular Ca+2 levels in hippocampal neurons, which remain elevated during the progression of the disease. However, the participation of ryanodine receptors (RyRs) in the neuronal loss and circuitry rewiring that take place in the hippocampus after SE remains unknown. In this context, we first investigated the functional role of RyRs on the expression of synaptic and plasticity-related proteins during epileptogenesis induced by pilocarpine in Wistar rats. Intrahippocampal injection of dantrolene, a selective pharmacological blocker of RyRs, caused the increase of the presynaptic protein synapsin I (SYN) and synaptophysin (SYP) 48 h after SE induction. Specifically, we observed that SYN and SYP were regulated in hippocampal regions known to receive synaptic inputs, revealing that RyRs could be involved in network changes and/or neuronal protection after SE induction. In order to investigate whether the changes in SYN and SYP were related to neuroplastic changes that could contribute to pathological processes that occur after SE, we evaluated the levels of activity-regulated cytoskeleton-associated protein (ARC) and mossy fiber sprouting in the dentate gyrus (DG). Interestingly, we observed that although SE induced the appearance of intense ARC-positive cells, dantrolene treatment did not change the levels of ARC in both western blot and immunofluorescence analyses. Accordingly, in the same experimental conditions, we were not able to detect changes in the levels of both pre- and post-synaptic plasticity-related proteins, growth associated protein-43 (GAP-43) and postsynaptic density protein-95 (PSD-95), respectively. Additionally, the density of mossy fiber sprouting in the DG was not increased by dantrolene treatment. We next examined the effects of intrahippocampal injection of dantrolene on neurodegeneration. Notably, dantrolene promoted neuroprotective effects by decreasing neuronal cell loss in CA1 and CA3, which explains the increased levels of synaptic proteins, and the apparent lack of positive effect on pathological plasticity. Taken together, our results revealed that RyRs may have a major role in the hippocampal neurodegeneration associated to the development of acquired epilepsy.
Genetic potential to improve seed and forage yield simultaneously in smooth bromegrass under water deficit conditions
EUPHYTICA
Authors: Saeidnia, F.; Majidi, M. M.; Mirlohi, A.
Abstract
This study was conducted to assess genetic potential of smooth bromegrass for water stress and to identify the association among different seed and forage production related traits. Thirty-six genotypes were clonally propagated and evaluated in the field under two moisture environments (normal irrigation and water stress) during 2013-2015. High variation was observed among genotypes for all of the measured traits. Water stress had negative effects on seed yield and its components and reduced genotypic variation of measured traits. On average, water stress reduced seed and forage yield by 38 and 14%, respectively. Genetic coefficient of variation for seed yield and its components was higher under stress, providing opportunities for a greater selection differential. The estimates of heritability were higher in normal condition than water stress condition for all of the evaluated traits, which is advantageous for successful selection. Moreover, the majority of seed yield components had higher heritability estimates than seed yield. The higher heritability estimates of some seed yield components, compared to SYP, suggests a potential for indirect selection. The results showed that selection for both forage and seed yield is possible simultaneously in normal irrigation as well as in water stress environment. Genotypes 7, 8, 26 and 27 had high forage yield, while genotypes 23 and 27 had high seed yield under both normal irrigation and water stress condition. Three genotypes ranked among the top three for both seed and forage yield and under both normal irrigation and water stress condition. They are promising parents for further use in developing improved cultivars by cross-breeding.