Biology subjects

Kadiri, Y.

Publications and source records attributed to Kadiri, Y..

4 recordsLinked to original sources

bioRxiv2023

Enhancing KCC2 function reduces interictal activity and prevents seizures in mesial temporal lobe epilepsy

The neuronal K/Cl cotransporter KCC2 regulates the transmembrane chloride gradient, which controls the efficacy of GABAergic signaling. In mesial temporal lobe epilepsy (mTLE) and other neurological disorders, reduced KCC2 expression or function can result in depolarizing GABA signaling, which is thought to contribute to pathological activity and seizures. Therefore, restoring chloride homeostasis represents a promising therapeutic strategy. We investigated the mechanisms and antiseizure effects of two small molecules, prochlorperazine (PCPZ) and CLP-257, that have been identified as potential KCC2 enhancers. We found that both compounds enhance KCC2 function and clustering in cortical neurons while reducing its membrane diffusion, without altering canonical regulatory phosphorylation. CLP-257 also selectively increased extrasynaptic, but not synaptic, GABAA receptor-mediated currents. Using in vitro recordings from resected brain tissue of patients with drug-resistant mTLE and in vivo recordings from a mouse model, we show that PCPZ and CLP-257 (or its prodrug CLP-290) effectively suppressed spontaneous epileptiform activity in both models. These findings reveal that PCPZ and CLP-257 act as genuine KCC2 enhancers and provide experimental evidence of the therapeutic potential of such compounds for treating drug-resistant mTLE. Significance statementA major challenge in treating epilepsy is the high percentage of patients with drug-resistant forms, like mesial temporal lobe epilepsy (mTLE). This study investigates a therapeutic strategy by targeting the neuronal KCC2 transporter, which is often dysfunctional in epilepsy. Our findings identify two compounds, prochlorperazine and CLP-257, that enhance KCC2 function by promoting its clustering on the cell membrane, a previously uncharacterized mechanism. Importantly, these compounds effectively reduce spontaneous epileptiform activity in human brain tissue from mTLE patients and significantly reduce seizure frequency in a mouse model. This work provides a critical proof-of-concept for activating KCC2 as a viable therapeutic approach for drug-resistant epilepsy.

neuroscience↗

bioRxiv2020

Host-mediated, cross-generational intraspecific competition in a multivoltine herbivore species

AO_SCPLOWBSTRACTC_SCPLOWConspecific insect herbivores co-occurring on the same host plant interact both directly through interference competition and indirectly through exploitative competition, plant-mediated interactions and enemy-mediated interactions. However, the situation is less clear when the interactions between conspecific insect herbivores are separated in time within the same growing season, as it is the case for multivoltine species. We hypothesized that early season herbivory would result in reduced egg laying and reduced performance of the next generation of herbivores on previously attacked plants. We tested this hypothesis in a choice experiment with box tree moth females (Cydalima perspectalis Walker, Lepidoptera: Crambidae). These females were exposed to box trees (Buxus sempervirens L., Buxaceae) that were either undamaged or attacked by conspecific larvae earlier in the season. We then compared the performance of the next generation larvae on previously damaged vs undamaged plants. Previous herbivory had no effect on oviposition behaviour, but the weight of next generation larvae was significantly lower in previously damaged plants. There was a negative correlation between the number of egg clutches laid on plants by the first generation and the performance of the next generation larvae. Overall, our findings reveal that early season herbivory reduces the performance of conspecific individuals on the same host plant later in the growing season, and that this time-lagged intraspecific competition results from a mismatch between the oviposition preference of females and the performance of its offspring.

ecology↗

bioRxiv2020

Insect herbivory on urban trees: Complementary effects of tree neighbours and predation

O_LIInsect herbivory is an important component of forest ecosystems functioning and can affect tree growth and survival. Tree diversity is known to influence insect herbivory in natural forest, with most studies reporting a decrease in herbivory with increasing tree diversity. Urban ecosystems, on the other hand, differ in many ways from the forest ecosystem and the drivers of insect herbivory in cities are still debated. C_LIO_LIWe monitored 48 urban trees from five species - three native and two exotic - in three parks of Montreal (Canada) for leaf insect herbivory and predator activity on artificial larvae, and linked herbivory with both predation and tree diversity in the vicinity of focal trees. C_LIO_LILeaf insect herbivory decreased with increasing tree diversity and with increasing predator attack rate. C_LIO_LIOur findings indicate that tree diversity is a key determinant of multitrophic interactions between trees, herbivores and predators in urban environments and that managing tree diversity could contribute to pest control in cities. C_LI This article has been peer-reviewed and recommended by Peer Community in Ecology https://doi.org/10.24072/pci.ecology.100061

ecology↗

bioRxiv2020

Search for top-down and bottom-up drivers of latitudinal trends in insect herbivory in oak trees in Europe

AimThe strength of species interactions is traditionally expected to become stronger toward the Equator. However, recent studies have reported opposite or inconsistent latitudinal trends in the bottom-up (plant quality) and top-down (natural enemies) forces driving insect herbivory, possibly because these forces have rarely been studied concomitantly. This makes previous attempts to understand the effect of large scale climatic gradients on insect herbivory unsuccessful. LocationEurope Time period2018-2019 Major taxa studiedQuercus robur MethodsWe used scholar-based citizen science to simultaneously test for latitudinal variation in plant-herbivore-natural enemy interactions. We further investigated the underlying climatic factors associated with variation in herbivory, leaf chemistry and attack rates in Quercus robur across its complete latitudinal range in Europe. We quantified insect herbivory and the occurrence of specialist herbivores as well as leaf chemistry and bird attack rates on dummy caterpillars on 261 oak trees. ResultsClimatic factors rather than latitude per se were the best predictors of the large-scale (geographical) variation in the incidence of gall-inducers and leaf-miners as well as of leaf nutritional quality. However, insect herbivory, plant chemical defences (leaf phenolics) and bird attack rates were not influenced by latitude or climatic factors. The incidence of leaf-miners increased with increasing concentrations of hydrolysable tannins and decreased with those of condensed tannins, whereas the incidence of gall-inducers increased with increasing leaf soluble sugar concentration and decreased with increasing leaf C:N ratios. However, neither other traits nor bird attack rates varied with insect herbivory. Main conclusionsThese findings help to refine our understanding of the bottom-up and top-down mechanisms driving geographical variation in plant-herbivore interactions, and urge for further examination of the drivers of insect herbivory on trees.

ecology↗