Elizaveta Plotnikova

Spinal cord injury (SCI) induces persistent locomotor deficits that are closely associated with maladaptive structural plasticity of spinal neuronal circuits. Although motor rehabilitation improves functional outcomes, the cellular substrates underlying rehabilitation-induced recovery remain incompletely understood, particularly in relation to activity-dependent neuromodulation strategies. Here, we investigated how treadmill-based motor training (TMT) and its combination with bioluminescent optogenetic (BL-OG) stimulation of Hb9 (homebox 9)-positive motoneurons and excitatory interneurons selectively modulate microarchitectural plasticity in the injured rat spinal cord. At the level of gross locomotor assessment, Basso, Beattie and Bresnahan (BBB) scores were comparable between the BL-OG and SCI+TMT groups. Although no statistically significant differences in the total score in rung ladder were observed at 28 days post-injury, animals in the BL-OG group showed a tendency toward a higher ratio of successful hindlimb placements, indicating improved step accuracy. BL-OG stimulation was associated with a slightly greater attenuation of SCI-induced spine abnormalities compared to TMT alone, with significant differences between the experimental groups detected specifically in laminae VIII and IX. These lamina-specific alterations in dendritic integration and dendritic spine composition were accompanied by preservation of wisteria floribunda agglutinin WFA-positive perineuronal net (PNN) architecture. Against this background, reduced glypican-4 (GPC-4) expression and attenuated WFA/GPC-4 colocalization were observed in the SCI+BL-OG group relative to SCI in laminae VII–IX, consistent with activity-dependent modulation of PNN-associated synaptic organization in Hb9-positive neuronal populations. Together, these findings indicate that motor rehabilitation and bioluminescent optogenetic stimulation engage distinct but partially overlapping mechanisms of activity-dependent microarchitectural remodeling, preferentially targeting synaptic and perineuronal net-associated substrates rather than inducing large-scale circuit reorganization. Further studies are warranted to elucidate the mechanisms underlying these distinct plasticity profiles.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative dis-ease caused by the expansion of cytosine–adenine–guanine (CAG) repeats in the ataxin-1 (ATXN1) gene, leading to toxic gain-of-function of the ataxin-1 (ATXN1) protein. This narrative review systematizes the clinical and genetic aspects of SCA1 and discusses key molecular and cellular mechanisms: the ATXN1-CIC ataxin-1-Capicua complex (ATXN1-CIC), the role of serine 776 (Ser776) phosphorylation, interactions with 14-3-3 proteins, transcriptional dysregulation, and critically analyzes experimental models of the disease in vivo and in vitro. In addition, it presents a descriptive quantitative analysis of the literature on in vivo SCA1 models, conducted using a defined search methodology with a cut-off date of 23 November 2025. For each model, phenotypic markers, molecular signatures, and applicability to preclinical testing tasks are summarized. A comparison of the models reveals their complementarity and outlines optimal research trajectories, including omics approaches and prospects for targeted antisense oligonucleotide (ASO) therapy, RNA interference (RNAi), and genome editing. The result is a practical guide for selecting a model in accordance with specific hypotheses and translational objectives.

Background. Spinal cord injury (SCI) leads to partial or complete loss of sensory and/or motor functions below the injury site due to neuron and glial cell death, axonal degeneration, and disruption of the blood-spinal cord barrier (BSCB). Motor rehabilitation presents a promising strategy for recovery after SCI, but its molecular and cellular mechanisms remain poorly understood, particularly in regions distant from the injury epicenter within the central pattern generator.The  aim of  the  study. To assess structural and molecular changes occurring in regions proximal (Th9) and distal (L₂) to the epicenter of SCI in rats (Th₈) during rehabilitation motor load.Materials and methods. SCI was induced in rats at the Th₈ level. Animals were divided into a control group (SCI) and a group subjected to motor rehabilitation (SCI + Rehab). Structural and molecular changes were evaluated in the thoracic (Th₉) and lumbar (L₂) regions. The number of preserved myelinated fibers was assessed using methylene blue staining, and BSCB disruption was evaluated through the epifluorescence of Evans blue dye. Quantitative PCR was used to analyze the mRNA expression of genes encoding proteins specific to perisynaptic astrocytic processes.Results. In the lumbar region (L₂), motor rehabilitation led to a greater number of myelinated fibers in the corticospinal tract compared to the control group. Astrong negative correlation (r = –0.761) was observed between Evans blue fluorescence and the area of preserved tissue in the Th₇–Th₉ region in rehabilitated animals; however, this relationship is not statistically significant. Molecular analysis revealed that rehabilitation did not affect astrocyte polarization into aneurotoxic phenotype or the alteration of perisynaptic processes in both proximal and distal regions.Conclusion. Motor rehabilitation promotes the preservation of myelinated fibers in the lumbar region and reduces BSCB damage in the area proximal to the SCI. However, rehabilitation does not affect astrocyte polarization or the expression of mRNA genes encoding proteins characteristic of perisynaptic astrocyte processes.

Introduction. Analysis of locomotor activity is essential in a number of biomedical and pharmacological research designs, as well as environmental monitoring. The movement trajectories of biological objects can be represented by time series exhibiting a complex multicomponent structure and non-stationary dynamics, thus limiting the effectiveness of conventional correlation and spectral time series analysis methods. Recordings obtained using markerless technologies are typically characterized by enhanced noise levels, including both instrumental noise and anomalous errors associated with false estimates of the location of the points of interest, as well as gaps in the trajectories, promoting an urgent need in the development of robust methods to assess the characteristics of locomotor activity.Aim. Development of robust methods for assessing the characteristics of locomotor activity capable of efficient processing of noisy recordings obtained by markerless video-based motion capture systems.Materials and methods. In order to assess the characteristics of locomotor activity, the relative movements of body parts of laboratory animals were analyzed using the stability metrics of the mutual dynamics of their trajectories, their relative delays, as well as the relative duration of the recording fragments when relatively stable mutual dynamics could be observed. The local maxima of the cross-correlation function of two body fragments, the minima of the standard deviation of the difference between their Hilbert phases, as well as their relative delays, were used as the metrics of mutual dynamics.Results. The considered phase metrics were shown to explicitly reflect changes in locomotor activity, while the assessment of time delays using phase metric was shown to be prone to periodic error. The above limitation could be largely overcome using the correlation metrics, assuming that phase and correlation metrics could be combined.Conclusion. The proposed robust methods provide stable estimates of the characteristics of locomotor activity based on markerless video capture recordings, altogether increasing the efficiency of diagnostic procedures and assessment of the therapeutic effect during rehabilitation.