The endogenous neuromodulator taurine is involved in the central regulation of numerous physiological processes. However, the functional significance of taurine in the medial prefrontal cortex (mPC), a key region for decision-making and emotion control, remains poorly understood. Using Sprague–Dawley rats, we investigated the role of taurine signaling in the mPC and the possible contribution of taurine–serotonergic interactions to fear memory generalization. As a fear model, we used a conditioned fear response (CFR) with differentiation of auditory cues—a conditioned cue (CS+) reinforced by footshocks (CFR Training) and a safe differentiation cue (CS–) (Differentiation). Extracellular serotonin (5HT) and taurine levels in the mPC were monitored by in vivo microdialysis coupled with high‑performance liquid chromatography. We found that CFR Training triggers taurine release in the mPC, which is absent during differentiation. Administration of 1 mM taurine into the mPC decreased basal 5HT levels in the mPC and reduced 5HT levels during CFR Training and Differentiation 1 tests. This treatment did not affect CFR acquisition or its primary generalization, as it did not alter the duration of freezing (a marker of pain stimulus expectancy) to CS+ and CS– on the day of CFR formation. Taurine administration into the mPC decreased CFR generalization 24 h later, manifested as reduced freezing duration to CS– in the Differentiation 2 test. Freezing to the unreinforced CS+ during CFR testing and anxiety‑like behavior in the elevated plus maze were unchanged after taurine administration. These novel data indicate, first, a natural enhancement of intercellular taurine signals in the mPC during CFR Training. Second, they demonstrate an inhibitory effect of taurine administered into the mPC on the formation of generalized fear memories and suggest a possible involvement of taurine–serotonergic influences in this process. The results expand our understanding of pharmacological means for modulating generalized fear.
Objective.Spinal muscular atrophy (SMA) is a genetic disorder that causes the progressive degeneration of spinal motor neurons, which can result in premature death. Restoring motor function in people with SMA is a serious issue. These individuals require lifelong motor rehabilitation to maintain their quality of life. A recent study showed that a two-week course of transcutaneous electrical spinal cord stimulation (tSCS) combined with physical therapy led to clinically significant improvements in Revised Upper Limb Module (RULM) and Hammersmith Functional Motor Scale Expanded (HFMSE), improved forced vital capacity (FVC), reduced joint contractures in people with SMA types 2 and 3 receiving gene therapy. It is unclear how long the benefits of a tSCS course last. This study aimed to determine the long-term effects of tSCS and to evaluate whether consecutive tSCS courses can improve or maintain motor activity in individuals with SMA types 2 and 3 receiving disease-modifying therapy.Approach.Case series involved nine individuals with SMA types 2 and 3 (aged 5-20 years). They underwent two consecutive courses of tSCS combined with motor task performance. Each course lasted two weeks, with a break of 3-15 months between courses. The RULM, HFMSE, FVC and a goniometric assessment of knee extension were recorded before and after each course.Main results.Significant improvements achieved during the first course did not deteriorate between the courses. The second course demonstrated significant improvements in HFMSE scores and FVC.Significance.This case series confirms the effectiveness of tSCS in motor rehabilitation for individuals with SMA types 2 and 3. It can be concluded that the effects of tSCS treatment last for 4-5 months. Consecutive courses with an interval of less than a year between them can likely improve motor activity in people with SMA types 2 and 3 who have received disease-modifying therapy.
Objective.Transspinal electrical direct current (DC) stimulation is a noninvasive method of modulating the activity of spinal cord neurons. However, the effects and their mechanisms remain unclear. A pivotal question pertains to the localization of the effects of transspinal stimulation. In this study, the effects of anodal DC stimulation (1.5 mA for 11 min) of cervical enlargement on the excitability of upper limb motoneuron pools and other networks are identified.Approach.This is achieved using the spinal motor evoked potentials (sMEP) evoked by impulse transspinal spinal cord electrical stimulation. This study assessed the proximal and distal muscles on both sides of the body.Main results.The present study identified lateralization of stimulation effects, with the most significant effects observed in the proximal shoulder muscles, i.e. the biceps brachii and triceps brachii (TB). The most significant changes in motor responses were observed in the TB 15 min after stimulation, with a strong lateralization of responses and a decrease in sMEP amplitude. Moreover, a general tendency for the sMEP to decrease for approximately one hour after the cessation of stimulation was also observed.Significance.Thus, we observe a unique and selective effect of stimulation on the spinal cord. Perhaps understanding the placement of electrodes and stimulation protocols may lead to improved effects.
Transcutaneous spinal cord stimulation (tSCS) is used in physiological research and clinical rehabilitation. The objective assessment of pain sensations when using different stimulation pulse waveforms remains one of the relevant challenges. The aim of this study was (1) to experimentally compare the pain sensations elicited by tSCS using single pulses of different waveforms, and (2) to evaluate the feasibility of using the galvanic skin response (GSR) as a pain marker in an experimental setup conventionally employed in tSCS studies. The study involved healthy male volunteers (n = 13) who underwent tSCS at the T11–T12 vertebral level using single pulses of four waveforms: monophasic non-modulated (MN), monophasic modulated at 5 kHz (MM), biphasic non-modulated (BN), and biphasic modulated (BM). Pulses of increasing intensity were delivered at a frequency of approximately 0.3 Hz up to the maximum tolerable intensity, but not exceeding 250 mA and no longer than 6 min. The maximum stimulation intensity for all pulse waveforms was about 240 mA. Pain intensity level was assessed using a visual analog scale (VAS) after the end of stimulation and instrumentally by continuous GSR recording. It was found that at maximum tSCS intensities, GSR values significantly increased compared to baseline values for all pulse waveforms. The greatest increase in GSR and the highest VAS scores were recorded during the stimulation with MN pulses. Self-reported VAS pain scores and the GSR increase during the stimulation with modulated pulses (MM and BM) were significantly lower compared to non-modulated pulses (MN and BN). Changes in GSR magnitude were consistent with self-reported pain scoring. These findings confirm that kilohertz-frequency pulse modulation increases tSCS tolerance, while continuous GSR recording provides reliable pain monitoring during functional experimental tSCS studies.
To ensure adequate tissue perfusion, along with a properly functioning endothelium that enables vasodilation, the rheological properties of blood, such as hematocrit, blood viscosity, erythrocyte (RBC) deformability and aggregation, are important components of the circulatory system. Experiments on Sprague–Dawley rats aged 4, 18, and 23 months have shown that with age, hematocrit decreases, plasma and blood viscosity increase, and the degree of RBC aggregation rises. The RBC deformability index also significantly increases, indicating a decline in cell deformability. Along with age-related changes in blood rheological properties, an increase in desquamated endothelial cell count was observed in the blood plasma, indicating endothelial dysfunction. Overall, such changes lead to impaired microcirculation. The age-related changes in blood rheological parameters, as recorded in our study, are consistent with the results of cerebral cortex perfusion using Doppler ultrasonography and indicate a deterioration in microcirculation. Rheological parameters, such as blood viscosity, the degree of RBC aggregation, and their deformability index, in rats change as early as 18 months of age and can serve as markers of age-related changes in healthy animals.
