With one in every four older adults living with T2D and one in every two older adults meeting the criteria for prediabetes, neuromuscular changes due to T2D are likely to impact functional activities in this population. Limited work in evaluating motor unit number and size across muscles in the upper extremity in persons with Type II Diabetes (T2D) exists, mostly due to the traditional belief bias that the upper extremity is relatively spared in T2D as compared to the lower extremities. The purpose of the current study was to evaluate motor unit number and size (using electrophysiological motor unit number index (MUNIX) and motor unit size index (MUSIX)) across the upper extremity in older adults with T2D (n = 13) as compared to healthy age- and sex-matched controls (n = 12). Persons with T2D presented with more motor units and larger motor unit sizes (p < 0.05) as compared to age- and sex-matched control participants. These changes were not dependent upon muscle location within a limb, indicating systemic neuromuscular changes associated with T2D. These group effects were clarified when health state covariates (e.g., blood pressure) were accounted for. Findings are consistent with emerging data that show altered neuromuscular characteristics with health state considerations in persons with T2D.

The medial prefrontal cortex (mPFC) is closely associated with various psychopathologies in humans, and its dysfunction is invariably accompanied by abnormalities in the serotonin (5-hydroxytryptamine, 5-HT) system of the brain. In this study, in-vivo extracellular recording techniques were used to investigate changes in the excitability of pyramidal neurons and interneurons in the rat mPFC following injection of 5,7-dihydroxytryptamine (5,7-DHT) into the bilateral lateral ventricles to damage the serotoninergic neurons. The levels of 5-HT in the mPFC and dorsal raphe nucleus of rats were determined by high-performance liquid chromatography. The results showed that the levels of 5-HT were significantly reduced in the mPFC and dorsal raphe nucleus two weeks after injection of 5,7-DHT into the bilateral lateral ventricles, relative to the normal group. The discharge frequency of pyramidal neurons in the mPFC was markedly increased compared to the normal group, with a significant rise in burst discharge, while the average discharge frequency of interneurons was significantly reduced and tended towards irregular activity. The results of the study indicated that the brain's 5-HT neurotransmitter system not only directly affects the activity of mPFC pyramidal neurons but also modulates the electrical activity of interneurons, thereby regulating the local microcircuitry within the mPFC and participating in its function.

A critical component in triggering and progressing autoimmune multiple sclerosis (MS) is the deregulation of immune responses, including dysfunction of T regulatory cells (Tregs), critical participants in the pathogenetic context of inflammation. It has been found that miRNAs have a crucial role in the induction of MS because dysregulation of miRNAs can result in defects in immunological tolerance. In this investigation, we examined the miR-10a contribution to MS disorder by comparing the altered expression of miR-10a in peripheral blood mononuclear cells (PBMCs) of 40 MS patients to 40 healthy controls. Additionally, we examined Tregs' frequency in MS patients in compare with healthy controls. We evaluated the secreted levels of anti-inflammatory cytokines, such as IL-10 and TGF-B, in the serum of MS patients and their expression level in healthy controls' and patients' peripheral blood mononuclear cells (PBMCs). Then, we assessed the correlation between miR-10a expression with Treg frequency and levels of anti-inflammatory cytokines in serum. PBMCs from MS patients had downregulated expression of miR-10a, and a substantial correlation was found between this expression and a reduction in Treg cells' frequency and the secreted anti-inflammatory cytokines associated with Tregs' diminished functionality. In summary, our research demonstrated a strong correlation between Tregs' frequency, lower levels of cytokines linked to Treg function, and lower expression of miR-10a in PBMCs. So, the alteration of miR-10a can be utilized as a probable therapeutic target for the prevention and management of MS disorder. However, further examination is requisite before this strategy become practical for use in the clinical setting.

To evaluate the effects of Ligustrazine (Lig) on nitroglycerin-induced migraine and explore the mechanism through the mitochondria-inflammation pathway.

Mesenchymal stem cell (MSC)-based therapy has been applied in several clinical trials of spinal cord injury (SCI). We have successfully established MSCs from human cranial bone and developed a longitudinal neuromonitoring technique for rodents. In addition to single transplantation, the potential of multiple transplantations has been suggested as a new therapeutic strategy. However, there are no reports on the electrophysiological effects of multiple MSC transplantations in SCI using transcranial electrical stimulation motor-evoked potentials (tcMEPs). Here, we aimed to elucidate the efficacy and mechanism of action of multiple MSC transplantations using tcMEPs. After establishing a weight-drop-induced SCI rat model, we performed repeated intravenous transplantation of human cranial bone-derived MSCs (hcMSCs) on days 1 and 3 post-SCI. Motor function and tcMEP recovery were evaluated 6 weeks post-transplantation. Tissue repair post-SCI was assessed using immunostaining for myelin and neurons in the injured posterior cord. Repeated hcMSC transplantation significantly improved motor function and electrophysiological recovery compared to single transplantation and control treatment. Repeated hcMSC transplantation promoted electrophysiological functional recovery by exerting a protective effect on the functional structure of pyramidal tract axons. Thus, acute-phase repeated transplantation could be a novel and effective therapeutic strategy for the clinical application of MSCs in SCI.

Cerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of Psoralea corylifolia Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear.

Nociception is defined as "the neural process of encoding noxious stimuli" by the International Association for the Study of Pain (IASP). Nociception relies on detecting noxious stimuli arising from a potentially or actually tissue-damaging event via specialized cells called nociceptors. In planarians, nociceptive behavior is often indicated by a 'scrunching' gait, in contrast to the usual gliding behavior displayed in normal conditions. The present study extends our previous study Reho et al. (2024) by testing a new potentially irritant molecule, Cinnamaldehyde (CA), which could induce scrunching gaits. We reproduced the nociceptive chemical tests from our previous study using CA instead of Allyl isothiocyanate (AITC) on Girardia dorotocephala (Gd) implementing an open field behavioral analysis. CA induced a dose-dependent increase in scrunching gait similar to the action of AITC and was expectedly partially suppressed by morphine and meloxicam. Knocking down the expression of the Gd-TRPA1 ion channel by RNA interference also suppressed the behavioral reaction to the molecule. In conclusion, we demonstrated that CA induced a nociceptive behavior in planarians through an action on the ion channel TRPA1.

DRG primary neuron cultures, derived from rodents, closely mimic properties of sensory neurons in vivo and are highly useful for studying pain and neurological disorders. These cultures are pivotal in patch-clamp electrophysiology for sensory neuron properties analysis. A detailed, replicable protocol in scientific research ensures experiment accuracy and reproducibility. This paper provides comprehensive details for replicating the protocol and achieving consistent results in primary DRG cell culture as used for patch-clamp recordings. We outlined a comprehensive protocol for establishing primary DRG cell culture, optimized for improved gigaseal formation in whole-cell patch-clamp recordings. Additionally, we conducted a simulation study focused on recording macroscopic K channels. The findings established an optimized novel protocol that works reliably for whole-cell patch-clamp recordings and data analysis using primary DRG cells prepared as described in this publication. The details for the protocol in the literature are dispersed across various publications, making it challenging to find a comprehensive summary in one source. This study confirms, for the first time, the efficacy of using fewer protocol steps, which reduces stress and variability in obtaining suitable cells for patch-clamp recordings compared to existing methods in the literature. Given the challenges posed by the dissociation process of primary DRG cells and the importance of comprehensive method documentation in the literature, the protocol presented provides improved and consistent applications of primary DRG cell culture in patch-clamp recordings.

Driving fatigue is a serious threat to driving safety. Therefore, it is of great significance to accurately detect driving fatigue. In this study, the generalized orthogonal partial directed coherence (gOPDC) algorithm, which measures the time-frequency domain interaction of electroencephalogram (EEG) signals, was used to accurately estimate the connectivity between cortical channels. The causal brain network of driver continuous driving is constructed. The results show that the clustering coefficient and global efficiency tend to decrease with the increase in driving time. Causal information flow in the left prefrontal, parietal, occipital regions and the right posterior frontal region increased significantly when subjects transitioned from awake to fatigued, while causal information flow in the right prefrontal, parietal, occipital regions and the left posterior frontal region decreased mutually significantly. Compared with the traditional driving fatigue algorithm, the accuracy of the method used in this paper is higher than the traditional methods.

Studies conducted on mammalian models have indicated the role of galanin-like peptide (GALP) in appetite regulation. For the first time, the present study examines the effects of this peptide on feed consumption and behavioral changes, as well as its interaction with dopaminergic and neuropeptide Y (NPY) systems in broilers. In experiment 1, broilers were injected with GALP (0.5, 1, and 2 μg) and saline. In experiment 2, saline, NPY1 receptor antagonist (BIBO-3304), GALP (2 μg), and BIBO-3304 + GALP were administrated. Experiments 3-6 were identical to experiment 2, except that NPY2 receptor antagonist (BIIE 0246), NPY5 receptor antagonist (CGP 71683A), D1 receptor antagonist (SCH39166), and D2 receptor antagonist (L-741,626) were injected instead of BIBO-3304. After that, cumulative meal consumption was recorded for 2 h. Also, behavioral changes in the broilers receiving GALP (0.5, 1, and 2 μg) were monitored for thirty minutes after infusion. Following the administration of GALP (1 and 2 μg), food intake and the number of feeding and exploratory pecks of chicks increased (P < 0.05), while other behaviors did not change significantly (P ≥  0.05). Co-infusion of BIBO-3304 + GALP suppressed the orexigenic effect of GALP (P < 0.05). Infusion of BIIE 0246, CGP 71683A, and L-741,626 with GALP, had no significant effect on GALP-induced hyperphagia (P ≥  0.05). However, the orexigenic effects of GALP were stimulated following the co-administration of SCH39166A + GALP (P < 0.05). These findings indicate that NPY1 and D1 receptors can mediate GALP-induced hyperphagia in broilers.

Prolonged periods of opioid use have been shown to cause neuroadaptations in the brain's reward circuitry, contributing to addictive behaviors and drug dependence. Recently, considerable focus has been placed on the role of the endocannabinoid system (ECS) and its CB receptors in opioid-driven behaviors. However, opioid-induced neuroadaptations to the ECS remain understudied. In this study, we systematically assessed CB1 receptor (CB1R) protein expression within the cortico-mesolimbic-basal ganglia circuit in rats following chronic fentanyl exposure. Male and female Long Evans rats were administered increasing daily doses of fentanyl or saline for 14 days. During naloxone-precipitated withdrawal, fentanyl-treated rats exhibited significantly higher withdrawal symptoms than saline-treated controls. Using Western Blotting, we demonstrated that the fentanyl-treated rats had significantly higher CB1R expression in the insula and significantly lower CB1R expression in the nucleus accumbens and substantia nigra compared to saline-treated rats. No significant differences in CB1R expression were detected between saline and fentanyl-treated rats in the prefrontal cortex, dorsal striatum, medial septum, hypothalamus, amygdala, hippocampus, ventral tegmental area, periaqueductal gray area, pedunculopontine tegmentum, and laterodorsal tegmentum (LDT). These findings suggest that chronic fentanyl exposure leads to region-specific neuroadaptations of CB1R protein expression in motivation- and addiction-associated brain regions.

Intracellular chloride (Cl) homeostasis is a critical regulator of neuronal excitability. Voltage-dependent neuronal Cl channels remain the least understood in terms of their role as a source of Cl entry controlling excitability. We have shown recently that striatal medium spiny neurons (MSNs) express a functional Cl conducting ClC-1-like channel with properties similar but not identical to native ClC-1 channels (Yarotskyy, V., Lark, A.R.S., Nass S.R., Hahn, Y.K., Marone, M.G., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2022) Am. J. Physiol. Cell. Physiol. 322 (2022) C395-C409). Using a myotonic SWR/J-Clcn1/J mouse model with a premature stop codon for the ClC-1 channel rendering it non-functional, we demonstrate that striatal MSNs isolated from wild type (wt) and homozygous mutant (adr) mouse embryos have identical voltage-dependent outwardly rectifying Cl currents. In contrast and as expected, homozygous adr skeletal muscle flexor digitorum brevis (FDB) fibers display nominal macroscopic Cl currents compared to heterozygous wild-type adr FDB fibers. Together, our findings demonstrate that the novel ClC-1-like channels in MSNs are unrelated to skeletal muscle-specific ClC-1 channels, and therefore represent a unique voltage-dependent neuronal Cl channel of unknown identity.

Fatty acid-binding protein 7 (FABP7) aids in the intracellular transport of endogenous cannabinoids and is involved in regulating the stress response system. This study examined the role of FABP7 in chronic stress exposure through the binding of CB1 receptors. Adult male FABP7 and FABP7 mice were treated with the unpredictable chronic mild stress (UCMS) procedure. After 28 days of treatment, mice were euthanized, and CB1 was measured with in vitro autoradiography using [3H] SR141716A. FABP7 mice, irrespective of stress treatment, showed reduced [3H] SR141716A binding in the amygdala, secondary somatosensory cortex, and ventral caudate putamen compared with the FABP7 mice. Additionally, FABP7 mice treated with UCMS exhibited a reduction in CB1 binding in the globus pallidus and ventral caudate putamen compared with UCMS-treated FABP7 mice. Genetic deletion of FABP7 can decrease CB1 expression in various brain regions; however, the underlying mechanism remains unclear.

In mammals, many Hymenopteran stings are characterized by pain, redness, and swelling - three manifestations consistent with nociceptive nerve fiber activation. The effect of a Western honeybee (Apis mellifera) venom on the activation of sensory C-fibers in mouse skin was studied using an innervated isolated mouse skin preparation that allows for intra-arterial delivery of chemicals to the nerve terminals in the skin. Our data show that honeybee venom stimulated mouse cutaneous nociceptive-like C-fibers, with an intensity (action potential discharge frequency) similar to that seen with a maximally-effective concentration of capsaicin. The venom had a stronger effect on chloroquine-sensitive C-fibers compared to chloroquine-insensitive C-fibers, an effect that was recapitulated with a wasp (Vespula spp.) venom. Blocking TRPV1 and TRPA1 channels did not influence the honeybee venom-induced C-fiber activation. The effect of the venoms on chloroquine-sensitive and -insensitive subpopulation of C-fiber terminals was mimicked by melittin but not apamin; two of peptide venom components. Chloroquine-sensitive C-fibers are stimulated as a consequence of mast cell activation. Melittin degranulated mast cells in mouse skin by a non-IgE and non-MrgprB2 mechanism, and this may explain the stronger activation of the chloroquine-sensitive C-fibers.

The cerebral cortex is connected to the striatum via the axons of the pyramidal glutamatergic neurons, and this pathway is intimately involved in motor function. In the striatum, glutamatergic afferents initiate the activity of GABAergic medium spiny neurons (MSNs). This study addressed whether traumatic brain injury (TBI) affects GABA and glutamate extracellular levels in the dorsal striatum as an indicator of effects on the cortico-striatal pathway, in rats with motor deficits and recovered animals. Animals were assigned to a sham group, a TBI-alone group, and a TBI + striatal injury group (local injection of a FeCl solution to mimic hemorrhagic lesion). In the TBI-alone and TBI + striatal injury groups, motor deficits were accompanied by decreased extracellular GABA and glutamate levels in the striatum at 3 days post-injury. The TBI + striatal injury group showed higher motor deficits, which lasted 7 days longer, and GABA levels were significantly different compared to the TBI alone group. At 18 days post-injury, in recovered rats from the TBI-alone group GABA and glutamate levels returned to control levels. Alterations in extracellular GABA and glutamate levels indicate damage to the cortico-striatal pathway, underscoring the importance of studying this pathway for treatment and recovery after TBI.

Depression is a pervasive mood disorder that continues to challenge researchers and clinicians worldwide. Caffeine and its derivatives have been studied for their neuroprotective and antidepressant effect. Current study aimed to explore the potential antidepressant effect of a caffeine derivative, Sy-2476 [4-(1, 3, 7-trimethyl-2, 6-dioxo-2, 3, 6, 7-tetrahydro-1H-purin-8-yl) benzo nitrile], in corticosterone-induced rat model of depression. Depression-like behaviour in rats was induced by administering 20 mg/kg hydrocortisone s.c for 21 days. Behavioural studies evaluated the potential antidepressant effect of caffeine derivative Sy-2476, its effect on cortisol levels, modulation of A1/A2 receptors mRNA expression and antioxidant assays. Treatment of rats with Sy-2476 exhibited robust antidepressant-like effects in corticosterone-exposed rats by increasing sucrose preference (p = 0.0002) while reducing immobility time (p = 0.0118) in the forced swim test. Sy-2476 also reduced lipid peroxidation and increased the level of antioxidant enzymes, including glutathione, catalase, and superoxide dismutase. Moreover, Sy-2476 significantly lowered cortisol levels (p = 0.0019) and up-regulated mRNA expression of A1 (p = 0.0001) and A2 receptors (p = 0.0016) compared to the corticosterone-only treated group. In conclusion, Sy-2476 showed an antidepressant effect primarily by suppressing serum cortisol levels, modulating the expression of adenosine receptors, and exhibiting antioxidant properties.

Sleep disturbance causes many health problems in humans worldwide. This study evaluated the effects and possible mechanisms of sclareol (SCL) and/or linalool (LIN) through in vivo and in silico studies. For this, young chicks SCL (5, 10, and 20 mg/kg) and/or LIN (50 mg/kg) were orally administered thirty minutes before to the thiopental sodium (TS)-induced chicks with or without the standard drug diazepam (DZP: 3 mg/kg). Incidence, onset, and duration of sleep were then noted. The results suggest that SCL dose-dependently increased the onset and decreased the duration of sleep in animals. In contrast, LIN50 significantly (p < 0.05) decreased onset and increased sleep duration. SCL20 combined with LIN50 and/or DZP3 modulated the sleep parameters in animals. In combination, LIN50 showed better effects with DZP3, where the percentage decrease in latency and increase in sleep duration were 54.20 and 168.65 %, respectively. SCL20 when combined with LIN50 + DZP3 also modulated the onset and duration of sleep in animals. Further, in silico studies suggest that SCL and LIN have binding affinities with the 6X3X protein of the GABA receptor (α1 and β2 subunits) of -6.9 and -6.8 kcal/mol, respectively. The standard drug DZP showed a binding affinity of -5.0 kcal/mol. Taken together, SCL may exert an angiogenic-like effect and antagonize LIN and/or DZP-mediated sedative effects in TS-induced chicks, possibly through the GABA receptor α1 and β2 subunits interaction pathway.

Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased. We utilized a transgenic mouse model of HIV that conditionally expresses HIV-1 Tat in the CNS to examine cognitive behaviors and the expression of biomarkers related to learning and memory in both sexes. Tat + males exhibited deficits in spatial learning/memory and object recognition, while Tat + females showed enhanced fear memory. We investigated the involvement of activity-regulated cytoskeleton-associated protein (Arc), which is induced by novel experience related to learning/memory. We observed hippocampal Arc induction following foot shock in Tat + females but not Tat + males. Hippocampal levels of Arc, amyloid β (Aβ) monomers/oligomers and pCREB were altered in a sex-specific manner. CREB activity, which is highly associated with Arc induction, was reduced only in Tat + males. Tat exposure also decreased Arc expression in cultured human neurons. Thus, HIV-1 Tat effects on CREB/Arc signaling may differ between sexes, contributing to differences in cognitive deficits observed here and in PLWH.

Electrocorticographic (ECoG) signals provide high-fidelity representations of sensorimotor cortex activation during contralateral hand movements. Understanding the relationship between independent and coordinated finger movements along with their corresponding ECoG signals is crucial for precise brain mapping and neural prosthetic development. We analyzed subdural ECoG signals from three adult epilepsy patients with subdural electrode arrays implanted for seizure foci identification. Patients performed a cue-based task consisting of thumb flexion, index finger flexion or a pinching movement of both fingers together. Broadband power changes were estimated using principal component analysis of the power spectrum. All patients showed significant increases in broadband power during each movement compared to rest. We created topological maps for each movement type on brain renderings and quantified spatial overlap between movement types using a resampling metric. Pinching exhibited the highest spatial overlap with index flexion, followed by superimposed index and thumb flexion, with the least overlap observed for thumb flexion alone. This analysis provides practical insights into the complex overlap of finger representations in the motor cortex during various movement types and may help guide more nuanced approaches to brain-computer interfaces and neural prosthetics.

Sevoflurane (Sev) is a common clinical anesthetic but may lead to cognitive impairment. This study aims to deconstruct the underpinning molecular mechanism involved in Sev-induced neurological damage.

Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by systemic inflammatory response syndrome (SIRS)-induced metabolic stress and multiple organ dysfunctions. Moreover, ICU-AW is one of the most important factors affecting the prognosis of patients with SIRS, Electrophysiological examination is an effective method for early identification and monitoring of the course of the disease and is essential for accurate diagnosis of critical illness neuromyopathy (CINM). The data-intensive ICU environment is ideal for implementing the similarity network fusion (SNF) method. The objective of this study was to establish and validate a ICU-AW predictive model in SIRS patients, providing a practical tool for early clinical prediction.