Biology subjects

Behra, M.

Publications and source records attributed to Behra, M..

3 recordsLinked to original sources

bioRxiv2022

The FMRF-NH2 Gated Sodium Channel of Biomphalaria glabrata: Localization and Expression Following Infection by Schistosoma mansoni

The neglected tropical disease schistosomiasis impacts the lives of over 700 million people globally. Schistosoma mansoni, the trematode parasite that causes the most common type of schistosomiasis, requires planorbid pond snails of the genus Biomphalaria to support its larval development and transformation to the form that can infect humans. A greater understanding of neural signaling systems that are specific to the Biomphalaria intermediate host could lead to novel strategies for parasite or snail control. This study characterized a Biomphalaria glabrata neural receptor that is gated by the molluscan neuropeptide FMRF-NH2. The Biomphalaria glabrata FMRF-NH2 gated sodium channel (Bgl-FaNaC) amino acid sequence was highly conserved with FaNaCs found in related gastropods, especially the planorbid Planorbella trivolvis (91% sequence identity). In common with the P. trivolvis FaNaC, the B. glabrata receptor exhibited a low affinity (EC50: 3 x 10-4 M) and high specificity for the FMRF-NH2 agonist. Its expression in the central nervous system, detected by immunohistochemistry and in situ hybridization, was widespread, with the protein localized mainly to neuronal fibers and the mRNA confined to cell bodies. Colocalization was observed with the FMRF-NH2 tetrapeptide precursor in some neurons associated with male mating behavior. At the mRNA level, Bgl-FaNaC expression in the visceral and left parietal ganglia decreased at 20 days post infection by S. mansoni and in the shedding phase. Altered FMRF-NH2 signaling could be vital for parasite survival and proliferation in its snail intermediate host.

neuroscience↗

bioRxiv2020

Cnr2 is important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

The role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong cnr2 expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in zebrafish larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Cav1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the structure of the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) mediated via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.

neuroscience↗

bioRxiv2019

Valeriana Officinalis Crude Extracts Impair Hair Cell Regeneration in Larval Zebrafish Lateral Line

Irreversible hair cell (HC) loss in the inner ear is the leading cause for hearing and balance disorders. Discovery of therapeutic molecules preventing HC death and promoting regeneration, which does not occur in mammals like it does in lower vertebrates, is of major interest. In fish, HCs are also found in a superficial mechano-sensory organ called the lateral line (LL). LL-HCs are exposed to surrounding waters and are accessible to waterborne molecules providing a potent mean to study in vivo HC stability and regeneration. Commercial small molecule libraries were tested in screens for HC survival and regeneration in zebrafish, but ethnobotanical pharmacopeias remain totally unexplored because of the challenge that such complex mixtures represent. A rapid and cost-effective first-pass assay informing about the regenerative potential of an extract is therefore critical before embarking on cumbersome purification steps. We chose to test Valerian crude root extracts (Val), which are typically composed of more than 150 different components, amongst which is a main and abundant compound: valeric acid (VA). VA discovery and purification led to the commercialization of a synthetic analog: Valproic acid (VPA) which is a first-line drug for epilepsy and bipolar disorders that was also shown to significantly hamper LL-HC regeneration. We reasoned that if Val is not toxic, it would elicit effects like VPA. Thus, we synchronously ablated HCs in 5-day post-fertilization (dpf) larvae and monitored regeneration over the following 3 days in the presence of Val at the highest well-tolerated concentration (Val1 = 1mg/ml), or VPA (= 150M) as previously published. Both treatments significantly decreased HC regeneration without affecting HC-survival suggesting a similar mode of action. Furthermore, Val application as early as 3dpf and prolonged for up to 4 days did not affect larval survival, indicating that reduced HC-regeneration was not due to overall toxicity. Taken together, Val and VPA-treatments displayed a comparable response in a simple and up-scalable HC-regeneration assay which is an in-first-pass potent approach for drug discovery.

pharmacology and toxicology↗