Biology subjects

Radyushkin, K.

Publications and source records attributed to Radyushkin, K..

5 recordsLinked to original sources

bioRxiv2026

Performance-impacting brain state maladaptation driving disease progression in early mouse and human neuroinflammation

The neuronal mechanisms driving progression in neuroinflammatory disorders from early relapse-remitting phases to later neurodegenerative phases remain largely elusive. Functional brain state shifts towards hyperactivity, persisting beyond relapses, represent an early maladaptive response. Here, in remission stage of an experimental autoimmune encephalitis (EAE) mouse model of RRMS, we identified a reduced excitability upon optogenetic stimulation in the brain stem, the area of active disease, while in the cortex a persistent cortical neuronal hyperactivity and synaptic remodeling emerged, accompanied with an increase of markers of early apoptosis. In contrast, hippocampal circuits, which undergo a functional state shift without hyperactivity, do not show increased apoptosis. Visual cortical networks showed a deterioration of the accuracy of encoding visual information and a decrease in the behavioural visual discrimination ability in mice. In RRMS patients in remission, we identified a reduced visual colour discrimination, indicating both the presence and the clinical relevance of early brain state maladaptation that may contribute to progression independent from relapse activity (PIRA). SummaryIn a RRMS model and in patients, impaired visual processing was reported, indicating brain state maladaptations, associated with persistent cortical hyperactivity, brain stem hypoactivity, synaptic remodeling, and apoptosis. These maladaptations might contribute to relapse-independent disease progression through sustained network dysfunction.

neuroscience↗

bioRxiv2023

Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring

Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17As action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated IL-17A transfer across the placental barrier and subsequent development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.

neuroscience↗

bioRxiv2022

Less is more - loss of EGFL7 improves memory by upregulation of VEGF-D

Neural stem cells reside in a specialized neurogenic niche of the hippocampus termed the subgranular zone. Throughout life, they give rise to adult-born neurons in the dentate gyrus thereby contributing to learning and memory. Here, we report that neurons together with neural stem and precursor cells secrete the neurovascular protein epidermal growth factor-like protein 7 (EGFL7) to shape this niche. EGFL7 knock-out in vivo promoted adult neurogenesis generating neurons forming additional spines which permanently integrated into the neural circuit until old age. RNA-sequencing identified the cytokine VEGF-D as a major molecular driver of this process in vivo. In behavioral studies EGFL7 knock-out mice displayed stronger maintenance of memory suggesting longer-lasting spatial memory and improved memory consolidation in the hippocampus by modulation of pattern separation in young and aged mice. Taken together, EGFL7 is an upstream regulator of the VEGF-D in adult neurogenesis and a key regulator of learning and memory.

neuroscience↗

bioRxiv2021

NECAB2 orchestrates an endosomal pathway of mitochondrial quality control at striatal synapses

Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control and repair. We found that global knockout of the neuronal calcium-binding protein 2 (NECAB2) in the mouse causes loss of striatal synapses and behavioral phenotypes related to striatal dysfunction such as reduced motivation and altered sensory gating. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller. They are characterized by increased respiration and superoxide production resulting in oxidative stress. This accumulation of dysfunctional mitochondria is caused by a defective assembly of mitochondria with early endosomes in a pathway that involves the small GTPase Rab5 and its guanine nucleotide exchange factor Alsin/ALS2. NECAB2 therefore participates in an endosomal pathway of mitochondrial stress response and repair important for striatal function.

neuroscience↗

bioRxiv2020

Dynamic longitudinal behavior in animals exposed to chronic social defeat stress

Chronic social defeat (CSD) can lead to impairments in social interaction and other behaviors that are supposed to model features of major depressive disorder (MDD). Not all animals subjected to CSD, however, develop these impairments, and maintained social interaction in some animals is widely used as a model for resilience to stress-induced mental dysfunctions. So far, animals have mainly been studied shortly (24 hours and 7 days) after CSD exposure and longitudinal development of behavioral phenotypes in individual animals has been mostly neglected. We have analyzed social interaction and novel object recognition behavior of stressed mice at different time points after CSD and have found very dynamic courses of behavior of individual animals. Instead of the two groups, resilient or susceptible, that are found at early time points our data suggest four groups with (i, ii) animals behaving resilient or susceptible at early and late time points, respectively (iii) animals that start susceptible and recover with time or (iv) animals that are resilient at early time points but develop vulnerability later on.

animal behavior and cognition↗