Biology subjects

Andreev, A.

Publications and source records attributed to Andreev, A..

5 recordsLinked to original sources

bioRxiv2025

Neuroprotective action of agonists and modulators of A 1 adenosine receptors upon hyperexcitation: mechanism of the antiepileptic activity and role of neuron-glial interaction

Hyperexcitation of neuronal networks is believed to be the main reason for the excitotoxic death of neurons in different central nervous system pathologies, including epilepsy, ischemic stroke, and traumatic brain injury. Gi-coupled receptors can be considered as promising targets for the development of new neuroprotectors. Here, we studied the anticonvulsant activity of the agonists and positive allosteric modulators (PAM) of A1 adenosine receptors (A1Rs). Our experiments demonstrate that A1R agonists, CCPA and N6-cyclohexyladenosine (N6-CHA), suppress hyperexcitation in three different in vitro models, including acute glutamate excitotoxicity, NH4Cl- and bicuculline-induced epileptiform activity. We have found that the inhibitory action of the agonists is mediated by the activation of not only the neuronal A1Rs but also the astrocytic receptors. In astrocytes, A1R agonists enhance GABA release, possibly via induction of calcium transients. Using inhibitory analysis, we have demonstrated that G{beta}{gamma}-mediated activation of phospholipase C and subsequent Ca2+ mobilization from internal stores are essential for generating calcium transients in astrocytes following N6-CHA application. We have shown first that Ca2+-dependent activation of protein kinase C, which is involved in the mechanism of GABA release by astrocytes, is a pivotal step in the realization of the antiepileptic action of A1R agonists. Moreover, using the model of epileptiform activity induced by GABAAR blockade, we have shown that PAMs, PD81723 and VCP171, also suppress hyperexcitation. Furthermore, using the picrotoxin-induced epilepsy model in mice, we demonstrated that A1R agonists exhibit significant anticonvulsant effects and improve animal survival. The PAMs PD81723 and VCP171, when administered one hour before seizure induction, did not significantly affect seizure severity or survival rates. However, chronic administration of VCP171 produced a pronounced anticonvulsant effect and significantly increased survival.. Importantly, PAMs provided therapeutic benefits without significantly affecting overall activity levels in mice. Thus, our study demonstrates that both agonists and PAMs of A1R can be considered as potential therapeutic agents with antiepileptic and neuroprotective activity.

neuroscience↗

bioRxiv2025

stk32a links sleep homeostasis to suppression of sensory and motor systems

Sleep is regulated by a homeostatic process and associated with an increased arousal threshold, but the genetic and neuronal mechanisms that implement these essential features of sleep remain poorly understood. To address these fundamental questions, we performed a zebrafish genetic screen informed by human genome-wide association studies. We found that mutation of serine/threonine kinase 32a (stk32a) results in increased sleep and impaired sleep homeostasis in both zebrafish and mice, and that stk32a acts downstream of neurotensin signaling and the serotonergic raphe in zebrafish. stk32a mutation reduces phosphorylation of neurofilament proteins, which are co-expressed with stk32a in neurons that regulate motor activity and in lateral line hair cells that detect environmental stimuli, and ablating these cells phenocopies stk32a mutation. Neurotensin signaling inhibits specific sensory and motor populations, and blocks stimulus-evoked responses of neurons that relay sensory information from hair cells to the brain. Our work thus shows that stk32a is an evolutionarily conserved sleep regulator that links neuropeptidergic and neuromodulatory systems to homeostatic sleep drive and changes in arousal threshold, which are implemented through suppression of specific sensory and motor systems.

neuroscience↗

bioRxiv2021

Open-Source Thermometer, Temperature Controller, and Light Meter for Use in Animal Facilities and During Experiments

Experiments with biological samples require precise control of environmental conditions. In our work we use zebrafish (Danio rerio) to understand the neurobiology of sleep, which requires precise control of temperature and lighting. Like many labs, lighting and temperature in the animal facility are centrally controlled in the building. During behavioral experiments and microscopy sessions, we use custom-built heating systems and perform occasional manual checks of conditions. However, without a system to precisely record conditions, gradual changes in temperature can go unnoticed for a long time, and temporary failures may be missed entirely. Here we present the design and characterization of affordable open-source tools to record temperature and light conditions during animal experiments using an Arduino microcontroller or a Raspberry Pi compact computer. The waterproof temperature sensor has high stability over 50 days of recording and is precise to 0.1{degrees}C. The Arduino device can be used through a common serial port interface for which we present code in Python and MATLAB. The Raspberry Pi version can be accessed through a web interface, for which we provide an installation guide. We use the device to record and review temperature and lighting conditions in two zebrafish animal facilities. We use our platform to add a water heating system to maintain temperature at 28{degrees}C during in vivo light-sheet imaging of larval zebrafish. We show that a change in temperature from 28{degrees}C to 32{degrees}C affects resting heart rate of the animal, highlighting the importance of maintaining and recording conditions. The protocols presented here do not require advanced engineering, fabrication, or software skills, and provide an approach to accurately record and report experimental conditions.

bioengineering↗

bioRxiv2020

Plant sedimentary ancient DNA from Far East Russia covering the last 28 ka reveals different assembly rules in cold and warm climates

Woody plants are expanding into the Arctic under a warming climate. The related impact on plant diversity is not well understood because we have only limited knowledge about plant assembly rules and because of a lack of time-series of plant diversity. Here, we applied sedimentary ancient DNA metabarcoding using the plant-specific g and h primers of the trnL gene to a sediment record from Lake Ilirney (central Chukotka Far Eastern Russia) covering the last 28 thousand years. Our results show that forb-dominated steppe-tundra and Saliceae-rich dwarf-shrub tundra communities dominated during the cold climate before 14 ka, while deciduous erect-shrub tundra was abundant during the warm period between 14 and 0 ka. Larix invasion during the late Holocene substantially lagged behind the period of densest vegetation and likely warmest period between 10 and 6 ka. Overall, we discovered the highest richness during 28-23 ka and a second richness peak during 13-10 ka: both periods are characterised by low shrub abundance. The richest communities during the cold pre-14 ka period were phylogenetically clustered, which probably originates from environmental filtering along with niche differentiation under limited resources. In contrast, the richest post-14 ka community was phylogenetically overdispersed, likely originating from an erratic recruitment process in the course of warming. Despite differences in timescale, some of our evidence can be relevant to arctic plant diversity changes. By analogy to the past, we expect a lagged response of tree invasion. In the long-term, ongoing expansion of deciduous shrubs will eventually result in a phylogenetically more diverse community but will also cause reduced plant taxonomic richness; however, richness may overshoot in the short-term.

ecology↗

bioRxiv2018

Selective volume illumination microscopy offers synchronous volumetric imaging with high contrast

Light field microscopy provides an efficient means to collect 3D images in a single acquisition, as its plenoptic detection captures an extended image volume in one snapshot. The ability of light field microscopy to simultaneously capture image data from a volume of interest, such as a functioning brain or a beating heart, is compromised by inadequate contrast and effective resolution, due, in large part, to light scattering by the tissue. Surprisingly, a major contribution to the image degradation is the signal scattered into the volume of interest by the typical wide-field illumination that excites the sample region outside the volume of interest. Here, we minimize this degradation by employing selective volume illumination, using a modified light sheet approach to illuminate preferentially the volume of interest. This minimizes the unavoidable background generated when extraneous regions of the sample are illuminated, dramatically enhancing the contrast and effective resolution of the captured and reconstructed images. Light Field Selective Volume Illumination Microscopy (LF-SVIM, SVIM for short) dramatically improves the performance of light field microscopy, and offers an unprecedented combination of synchronous z-depth coverage, lateral and axial resolution, and imaging speed.

biophysics↗