Biology subjects

Matera, C.

Publications and source records attributed to Matera, C..

4 recordsLinked to original sources

bioRxiv2021

Fast photoswitchable molecular prosthetics control neuronal activity in the cochlea

Artificial control of neuronal activity enables studies of neural circuits and restoration of neural function. Direct, rapid, and sustained photocontrol of intact neurons could overcome shortcomings of established electrical stimulation such as poor selectivity. We have developed fast photoswitchable ligands of glutamate receptors to establish such control in the auditory system. The new photoswitchable ligands produced photocurrents in untransfected neurons upon covalently tethering to endogenous glutamate receptors and activating them reversibly with visible light pulses of few milliseconds. As a proof of concept of these molecular prostheses, we apply them to the ultrafast synapses of auditory neurons of the cochlea that encode sound and provide auditory input to the brain. This drug-based method affords kilohertz rate stimulation of auditory neurons of adult gerbils without genetic manipulation that would be required for their optogenetic control. The new photoswitchable ligands are also broadly applicable to spatiotemporally control fast spiking interneurons in the brain.

neuroscience↗

bioRxiv2019

Novel Analgesic Agents Obtained by Molecular Hybridization of Orthosteric and Allosteric Ligands

Despite the high incidence of acute and chronic pain in the general population, the efficacy of currently available medications is unsatisfactory. Insufficient management of pain has a profound impact on the quality of life and can have serious physical, psychological, social, and economic consequences. This unmet need reflects a failure to develop novel classes of analgesic drugs with superior clinical properties and lower risk of abuse. Nevertheless, recent advances in our understanding of the neurobiology of pain are offering new opportunities for developing different therapeutic approaches. Among those, the activation of M2 muscarinic acetylcholine receptors, which play a key role in the cholinergic regulation of the nociceptive transmission, constitutes one of the most promising strategies. We have recently developed a small library of novel pharmacological agents by merging the structures of known orthosteric and allosteric muscarinic ligands through their molecular hybridization, an emerging approach in medicinal chemistry based on the combination of pharmacophoric moieties of different bioactive substances to produce a new compound with improved pharmacological properties. Herein we report the functional characterization of the new ligands in vitro and the assessment of their efficacy as analgesic agents and tolerability in mice. This work provides new insights for the development and optimization of novel muscarinic hybrid compounds for the management of pain.

pharmacology and toxicology↗

bioRxiv2019

Control of brain state transitions with light

Behavior is driven by specific neuronal activity and can be directly associated with characteristic brain states. The oscillatory activity of neurons contains information about the mental state of an individual, and the transition between physiological brain states is largely controlled by neuromodulators. Manipulating neural activity, brain rhythms or synchronization is of significant therapeutic interest in several neurological disorders and can be achieved by different means such as transcranial current and magnetic stimulation techniques, and by light through optogenetics, although the clinical translation of the latter is hampered by the need of gene therapy. Here, we directly modulate brain rhythms with light using a novel photoswitchable muscarinic agonist. Synchronous slow wave activity is transformed into a higher frequency pattern in the cerebral cortex both in slices in vitro and in anesthetized mice. These results open the way to the study of the neuromodulation and control of spatiotemporal patterns of activity and pharmacology of brain states, their transitions, and their links to cognition and behavior, in different organisms without requiring any genetic manipulation.

neuroscience↗

bioRxiv2018

Host factors influence the sex of nematodes parasitizing roots of Arabidopsis thaliana

Plant-parasitic cyst nematodes induce hypermetabolic syncytial nurse cells in the roots of their host plants. Syncytia are their only food source. Cyst nematodes are sexually dimorphic, with their differentiation into male or female strongly influenced by host environmental conditions. Under favorable conditions with plenty of nutrients, more females develop, whereas mainly male nematodes develop under adverse conditions such as in resistant plants. Here, we developed and validated a method to predict the sex of beet cyst nematode (Heterodera schachtii) during the early stages of its parasitism in the host plant Arabidopsis thaliana. We collected root segments containing male-associated syncytia (MAS) or female-associated syncytia (FAS), isolated syncytial cells by laser microdissection, and performed a comparative transcriptome analysis. Genes belonging to categories of defense, nutrient deficiency, and nutrient starvation were overrepresented in MAS as compared to FAS. Conversely, gene categories related to metabolism, modification, and biosynthesis of cell walls were overrepresented in FAS. We used {beta}-glucuronidase (GUS) analysis, qRT-PCR, and loss-of-function mutants to characterize FAS- and MAS-specific candidate genes. Our results demonstrated that various plant-based factors, including immune response, nutrient availability, and structural modifications, influence the sexual fate sex determination of cyst the nematodes.

plant biology↗