Changes In Locomotion Research Articles

Structure-Activity Relationship of 7-Chloro-4-(Phenylselanyl) Quinoline: Novel Antinociceptive and Anti-Inflammatory Effects in Mice.

The 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) stands out for its potential antinociceptive and anti-inflammatory activities. Thus, in this study we investigated the structure-activity relationship of 4-PSQ and its analogues 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl}quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl)selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, as well as by in silico methods. The compoundsa(-F),b(-CF3),c(-Bis-CF3),d(-CH3),e(-OOH) and 4-PSQ exert antinociceptive effects in chemical and thermal nociception models, except compoundsd(-CH3) ande(-OOH) that did not show antinociceptive effects in the hot plate test. In addition, treatments with all compounds did not cause locomotor changes in mice. In silico datathe compounds revealed that only compoundc(Bis-CF3) exhibited low gastrointestinal absorption and that compoundsc(Bis-CF3) ande(-OOH) do not have the ability to penetrate the blood-brain barrier, indicating that compounde(-OOH) did not produce a central antinociceptive effect. Furthermore, we found that this class of compounds has a higher affinity for COX-2 than for COX-1. In general, our data indicate that the insertion of substituents can alter the efficiency of 4-PSQ as an antinociceptive and anti-inflammatory agent.

Toxicological analysis of chronic exposure to polymeric nanocapsules with different coatings in Drosophila melanogaster

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 μL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 μL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 μL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

VGF modifications related to nigrostriatal dopaminergic neurodegeneration induced by the pesticide fipronil in adult male rats

BackgroundDopamine is reduced in the brain of rats treated with fipronil, a broad-spectrum insecticide. VGF (no acronym) is a neurotrophin-inducible protein expressed as the 75 kDa form (precursor or pro-VGF) or its truncated peptides. VGF immunostaining has been revealed using an antibody against the C-terminal nonapeptide of the rat pro-VGF in the nerve terminals of the rat substantia nigra, where it was reduced after 6-hydroxydopamine treatment. It is unknown whether pro-VGF and/or its shortened peptides are present in these neurons. Therefore, the aim of this study was first to determine which types of VGF are expressed in the normal substantia nigra (and striatum) and then to determine VGF modulations and whether they occur in parallel with locomotor changes after fipronil injection. MethodsRats were divided into two groups that received a unilateral intranigral infusion of either fipronil (25 µg) diluted in dimethyl sulfoxide (DMSO) or DMSO alone, and then were tested for locomotor activity. An untreated group of rats (n=4) was used for identification of the VGF fragments using high performance liquid chromatography-mass spectrometry and western blot, while changes in treated groups (fipronil vs DMSO, each n=6) were investigated by immunohistochemistry using an antibody against the rat pro-VGF C-terminal nonapeptide in parallel with the anti-tyrosine hydroxylase antibody. ResultsIn untreated rats, the VGF C-terminal antibody identified mostly a 75 kDa band in the substantia nigra and striatum, supporting the finding of high-resolution mass spectrometry, which revealed fragments covering the majority of the pro-VGF sequence. Furthermore, several shortened VGF C-terminal forms (varying from 10 to 55 kDa) were also found by western blot, while high-resolution mass spectrometry revealed a C-terminal peptide overlapping the immunogen used to create the VGF antibody in both substantia nigra and striatum. In the substantia nigra of fipronil-treated rats, immunostaining for tyrosine hydroxylase and VGF was reduced compared to DMSO-treated rat group, and this was related with significant changes in locomotor activity. ConclusionFipronil has the ability to modulate the production of pro-VGF and/or its C-terminal truncated peptides in the nigrostriatal system indicating its intimate interaction with the dopaminergic neurotransmission and implying a potential function in modulating locomotor activity.

Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

Neuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI's direct effect on attention. Using the rodent continuous performance task (CPT), we assessed PSI's effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes. In the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3mg/kg), TCB-2 (0.3, 1, and 3mg/kg), or M100907 (0.1, 0.3, and 1mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured. In the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections. Psilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.

Evaluation of anti-inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights.

Kaurenol, a diterpene alcohol found in Copaifera langsdorffii Desf. (known as "copaiba"), is historically used in traditional medicine for inflammatory conditions. This study aims to comprehensively assess the potential anti-inflammatory and antinociceptive properties of kaurenol. To this end, the following experiments were conducted to evaluated toxicity: locomotor performance and acute toxicity; nociception: acetic acid-induced writhing and formalin-induced antinociception; and anti-inflammatory activity: carrageenan and dextran-induced paw edema at 10, 20, and 40 mg/kg, and measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in macrophages at 1, 3, and 9 μg/ml. Kaurenol did not show significant locomotor changes, acute toxicity, and central analgesic activity in the first phase of formalin test at dosages tested. Kaurenol showed 53%, 64%, 64%, and 58% of inhibition in the acetic acid-induced writhing, second phase of formalin test, carrageenan and dextran-induced paw edema, respectively. The anti-inflammatory activity was associated with the regulation of NO release and probably with the regulation of mediators, such as serotonin and prostaglandin in vascular permeability, as well as by being associated with the regulation of IL-6 and IL-10. Kaurenol display anti-inflammatory activity but has no analgesic activity.

Modulation of Autophagy and Nitric Oxide Signaling via Glycyrrhizic Acid and 7-Nitroindazole in MPTP-induced Parkinson’s Disease Model

Background Parkinson’s disease (PD) is characterized by dopaminergic (DA) neuron loss, Lewy body build-up, and motor dysfunction. One of the primary pathogenic mechanisms of PD development is autophagy dysfunction and nitric oxide-mediated neurotoxicity. Purpose The current study focuses on autophagy and nitric oxide (NO) signaling roles in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated PD mice and their protection by their modulators. Method BALB/c mice were administered MPTP (30 mg/kg/i.p/day) for five consecutive days in order to create a PD model. Following MPTP poisoning, the doses of GA (16.8 mg/kg/day/i.p.), 7-nitroindazole (7-NI) (10 mg/kg/day/i.p.), and their combination were administered once daily for 14 days. Animals were observed for behavioral and locomotor changes, biochemical examination, inflammatory mediators, and analysis of molecular markers. Results GA, 7-NI alone significantly reduced MPTP-induced locomotor, behavioral, and oxidative damage. Additionally, in MPTP-intoxicated animals, 7-NI and GA had protective effects on dopamine levels, TH positive DA neurons, inflammatory cytokines interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (Cox-2) concentration. Furthermore, GA increases LC3BII expression, which in turn increases autophagy. It also decreases total NO content, and a significant response of 7-NI demonstrates their interaction, which is neuroprotective. Conclusion Present research suggests that dysregulation of autophagy and NO-mediated neuroinflammation are involved in the pathogenesis and progression of MPTP-induced PD. The use of two pharmacotherapeutics, GA and 7-NI, respectively, significantly reduces MPTP-induced PD distortions and their interaction enhances the overall protective effect, suggesting that these pharmacological agents may be used for the treatment of PD.

Guanosine treatment prevents lipopolysaccharide-induced depressive-like behavior in mice

Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.

Intranasal administration of interleukin-4 ameliorates depression-like behavior and biochemical alterations in mouse submitted to the chronic unpredictable mild stress: modulation of neuroinflammation and oxidative stress.

Physical and psychological stress modulates the hypothalamic pituitary adrenal (HPA) axis, and the redox and inflammatory systems. Impairments in these systems have been extensively reported in major depression (MD) patients. Therefore, our study aimed to investigate the effects of the intranasal administration of interleukin-4 (IL-4) in mice with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) for 28days. On the 28th day, mice received IL-4 intranasally (1ng/mouse) or vehicle (sterile saline), and after 30min, they were submitted to behavioral tests or euthanasia for blood collection and removal of the adrenal glands, axillary lymph nodes, spleen, thymus, prefrontal cortices (PFC), and hippocampi (HC). A single administration of IL-4 reversed CUMS-induced depression-like behavior in the tail suspension test and splash test, without evoking locomotor changes. IL-4 administration reduced the plasma levels of corticosterone and the increased weight of suprarenal glands in stressed mice. Moreover, IL-4 restored the expression of nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor kappa B (NF-kB), interleukin 1 beta (IL-1β), IL-4, brain derived neurotrophic factor (BDNF), and indoleamine 2,3-dioxygenase (IDO) in the PFC and HC and modulated oxidative stress markers in these brain structures in stressed mice. Our results showed for the first time the antidepressant-like effect of IL-4 through the modulation of neuroinflammation and oxidative stress. The potential effect of IL-4 administered intranasally arises as an innovative strategy for MD treatment.

Abstract TP240: The Change Of Motor Functions After Post-stroke In 5xfad

Background and Rationale: Recent Alzheimer’s disease (AD) studies with 5XFAD, a mouse model of Alzheimer’s disease, were mainly focused on cognitive functions. Here, to investigate the change of motor functions after post-stroke in the AD mouse model, we generated the 5XFAD mice and examined their long-term behavior changes. Methods: To determine the role of 5XFAD after post-stroke, we generated the 5XFAD mice, induced the Ischemia/Reperfusion (30-minute middle cerebral artery occlusion (MCAO)/14 days reperfusion after 30-minute MCAO induction) injury model in mice, and tested the several behavior effects of 5XFAD (2 months vs. 6 months). Relative cerebral blood flow was measured by Laser Doppler. We daily investigated neurological deficit score, wire-hanging test with both time latency and grip score, and cylinder test for 14 days. Results: We found that CBF changes and brain shrinkages at 14 days after post-stroke were not changed in 5XFAD mice compared to the littermate control. The daily locomotor changes of neurological deficit score for 14 days were not significantly worsened compared to the littermate control. The Cylinder test shows that locomotor abnormalities were not changed in 5XFAD mice. The Wire-hanging test shows that locomotor abnormalities both latency and grip scores were worsened in 5XFAD mice compared to littermate control. Conclusion: These findings indicate that the long-term abnormalities of locomotor in 5XFAD mice may be an important therapeutic target for post-stroke in AD.

Abstract TP232: The Change Of Long-term Motor Functions After Post-stroke In Neuronal Cell Specific Sirt1 Knock-in Mice

Background and Rationale: Ischemic stroke is one of the leading causes of morbidity and mortality. Sirt1 is an NAD+ dependent deacetylase known as an important regulator for stroke research. During ischemia, the expression of total Sirt1 is regulated down. To investigate the change of motor function in neuronal-specific Sirt1 overexpression, we generated the neuronal-specific Sirt1 knock-in (nSirt1 KI) mice and examined its behavior effect after post-stroke. Methods: To determine the role of Sirt1 in ischemic stroke, we tested the pharmacological effects of metformin and sirtinol, and to investigate the genetic role of neuronal Sirt1 in the brain, we generated the nSirt1 KI mice and induced the Ischemia/Reperfusion (I/R: 30 min. middle cerebral artery occlusion (MCAO)/1D-14D reperfusion after 30 min. MCAO) injury model. Infarction volume was measured by TTC staining and relative cerebral blood flow was measured by Laser Doppler. We also determined neurological deficit score (NDS), wire-hanging test, and cylinder test at 1D-14D after 30 min. MCAO. Protein levels from brain lysates in the cerebral cortex and hippocampus were studied by western blotting. Results: nSirt1 KI mice exhibited increased rCBF and reduced infarction volume compared to that of littermate control in I/R injury model. Based on western blotting analysis of brain tissue lysates in nSirt1 KI mice, the expression of Sirt1 was significantly increased by ~5 times. Overexpression of Sirt1 reduced infarction volume was reversed by sirtinol. The daily locomotor changes of neurological deficit score for 14 days were significantly changed compared to the littermate control. The Wire-hanging test shows that locomotor abnormality was improved in nSirt1 KI mice compared to littermate control. The Cylinder test shows that locomotor abnormality was improved in nSirt1 KI mice. We found that brain shrinkages at 14 days after post-stroke were not severe in nSirt1 KI mice compared to the littermate control. Conclusion: These findings indicate that the long-term enhancement of motor functions in neuronal Sirt1 overexpression may be an important therapeutic target for post-stroke and long survival.

Electrical Stimulation of Distal Tibial Nerve During Stance Phase of Walking May Reverse Effects of Unilateral Paw Pad Anesthesia in the Cat.

Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and the lack of this feedback results in motor deficits. We tested the hypothesis that locomotor changes caused by local unilateral anesthesia of paw pads in the cat could be reduced/reversed by electrical stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve during stance. Several split-belt conditions were investigated in four adult female cats. In addition, we investigated the effects of similar distal tibial nerve stimulation on overground walking of one male cat that had a transtibial, bone-anchored prosthesis for 29months and, thus, had no cutaneous/proprioceptive feedback from the foot. In all treadmill conditions, cats walked with intact cutaneous feedback (control), with right fore- and hindpaw pads anesthetized by lidocaine injections, and with a combination of anesthesia and electrical stimulation of the ipsilateral distal tibial nerve during the stance phase at 1.2× threshold of afferent activation. Electrical stimulation of the distal tibial nerve during the stance phase of walking with anesthetized ipsilateral paw pads reversed or significantly reduced the effects of paw pad anesthesia on several kinematic variables, including lateral center of mass shift, cycle and swing durations, and duty factor. We also found that stimulation of the residual distal tibial nerve in the prosthetic hindlimb often had different effects on kinematics compared with stimulation of the intact hindlimb with paw anesthetized. We suggest that stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve provides functionally meaningful motion-dependent sensory feedback, and stimulation responses depend on limb conditions.

Systemic Rotenone Administration Causes Extra-Nigral Alterations in C57BL/6 Mice.

Systemic administration of rotenone replicates several pathogenic and behavioural features of Parkinson's disease (PD), some of which cannot be explained by deficits of the nigrostriatal pathway. In this study, we provide a comprehensive analysis of several neurochemical alterations triggered by systemic rotenone administration in the CNS of C57BL/6 mice. Mice injected with either 1, 3 or 10 mg/kg rotenone daily via intraperitoneal route for 21 days were assessed weekly for changes in locomotor and exploratory behaviour. Rotenone treatment caused significant locomotor and exploratory impairment at dosages of 3 or 10 mg/kg. Molecular analyses showed reductions of both TH and DAT expression in the midbrain, striatum and spinal cord, accompanied by altered expression of dopamine receptors and brain-derived neurotrophic factor (BDNF). Rotenone also triggered midbrain-restricted inflammatory responses with heightened expression of glial markers, which was not seen in extra-nigral regions. However, widespread alterations of mitochondrial function and increased signatures of oxidative stress were identified in both nigral and extra-nigral regions, along with disruptions of neuroprotective peptides, such as pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and activity-dependent neuroprotective protein (ADNP). Altogether, this study shows that systemic rotenone intoxication, similarly to PD, causes a series of neurochemical alterations that extend at multiple CNS levels, reinforcing the suitability of this pre-clinical model for the study extra-nigral defects of PD.

Do femoral biomechanical properties follow locomotor changes in primates? An ontogenetic study of olive baboons (Papio anubis)

AbstractObjectivesThe locomotor repertoire of the olive baboon (Papio anubis) changes during ontogeny from a diversified pattern in infancy to a stereotyped pattern in adults. On the assumption that the femoral diaphysis adapts to variations in the loading regime, we aimed to evaluate the impact of locomotor changes on femoral biomechanical properties during the ontogeny of olive baboons.Materials and MethodsWe used the cross‐sectional geometry of 50 three‐dimensional‐reconstructed olive baboon femora of an ontogenetic sample including individuals from birth to 28 years of age and belonging to a single social group. Cross section parameters were extracted, and cortical thickness maps were produced from 20% to 80% of the femoral length.ResultsNewborns present a distribution of cortical thickness that is longitudinally symmetric and anteroposterior shaped cross sections at midshaft. From this condition, infants, juveniles and adults femoral diaphyses are all characterized by a proximal shift in cortical thickness and a mediolateralization of bending rigidity and strength at midshaft.DiscussionAs soon as locomotor autonomy is established and despite a combination of several significant locomotor modes, the biomechanical pattern remains stable during ontogeny. Our results do not reflect the changes in locomotor repertoires that occur during ontogeny of Papio anubis. We therefore advise caution when inferring complex locomotor behavior from femoral biomechanical properties.

Mastery motivational climate intervention: Motor and social benefits for children with and without disabilities

This mixed-design study examined the effects of a mastery motivational climate intervention on the motor and social skills of underserved children with and without disabilities. A mastery climate was implemented for the intervention group consistent with the TARGET structure. Children, 24 children with disabilities (12 boys, 12 girls) and 52 without disabilities (31 boys, 21 girls), were assessed with the Test of Gross Motor Development –second edition pre-and post-intervention. Along with the intervention, social skills were assessed using a qualitative approach; a checklist with five levels of personal e social responsibility behavior was used. Results showed that mastery motivational climate intervention was effective in promoting positive changes in locomotor and object control scores; the intervention group also showed higher performance in the post-intervention than the control group. Along with the intervention, the children in the mastery motivational climate group also adopted higher personal and social responsibility levels during the lessons. Positive correlations were observed between children’s motor development and their levels of responsibility. The mastery motivational climate intervention promotes positive motor and social skills changes for children living in vulnerability.

Chemogenetic modulation of sensory afferents induces locomotor changes and plasticity after spinal cord injury.

Neuromodulatory therapies for spinal cord injury (SCI) such as electrical epidural stimulation (EES) are increasingly effective at improving patient outcomes. These improvements are thought to be due, at least in part, to plasticity in neuronal circuits. Precisely which circuits are influenced and which afferent classes are most effective in stimulating change remain important open questions. Genetic tools, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), support targeted and reversible neuromodulation as well as histological characterization of manipulated neurons. We therefore transduced and activated lumbar large diameter peripheral afferents with excitatory (hM3Dq) DREADDs, in a manner analogous to EES, in a rat hemisection model, to begin to trace plasticity and observe concomitant locomotor changes. Chronic DREADDs activation, coupled with thrice weekly treadmill training, was observed to increase afferent fluorescent labeling within motor pools and Clarke's column when compared to control animals. This plasticity may underlie kinematic differences that we observed across stages of recovery, including an increased and less variable hindquarters height in DREADDs animals, shorter step durations, a more flexed ankle joint early in recovery, a less variable ankle joint angle in swing phase, but a more variable hip joint angle. Withdrawal of DREADDs agonist, clozapine-N-oxide (CNO) left these kinematic differences largely unaffected; suggesting that DREADDs activation is not necessary for them later in recovery. However, we observed an intermittent “buckling” phenomenon in DREADDs animals without CNO activation, that did not occur with CNO re-administration. Future studies could use more refined genetic targeted of specific afferent classes, and utilize muscle recordings to find where afferent modulation is most influential in altering motor output.

A new elpistostegalian from the Late Devonian of the Canadian Arctic

A fundamental gap in the study of the origin of limbed vertebrates lies in understanding the morphological and functional diversity of their closest relatives. Whereas analyses of the elpistostegalians Panderichthys rhombolepis, Tiktaalik roseae and Elpistostege watsoni have revealed a sequence of changes in locomotor, feeding and respiratory structures during the transition1–9, an isolated bone, a putative humerus, has controversially hinted at a wider range in form and function than now recognized10–14. Here we report the discovery of a new elpistostegalian from the Late Devonian period of the Canadian Arctic that shows surprising disparity in the group. The specimen includes partial upper and lower jaws, pharyngeal elements, a pectoral fin and scalation. This new genus is phylogenetically proximate to T. roseae and E. watsoni but evinces notable differences from both taxa and, indeed, other described tetrapodomorphs. Lacking processes, joint orientations and muscle scars indicative of appendage-based support on a hard substrate13, its pectoral fin shows specializations for swimming that are unlike those known from other sarcopterygians. This unexpected morphological and functional diversity represents a previously hidden ecological expansion, a secondary return to open water, near the origin of limbed vertebrates.

Variation in human 3D trunk shape and its functional implications in hominin evolution

This study investigates the contribution of external trunk morphology and posture to running performance in an evolutionary framework. It has been proposed that the evolution from primitive to derived features of torso shape involved changes from a mediolaterally wider into a narrower, and antero-posteriorly deeper into a shallower, more lightly built external trunk configuration, possibly in relation to habitat-related changes in locomotor and running behaviour. In this context we produced experimental data to address the hypothesis that medio-laterally narrow and antero-posteriorly shallow torso morphologies favour endurance running capacities. We used 3D geometric morphometrics to relate external 3D trunk shape of trained, young male volunteers (N = 27) to variation in running velocities during different workloads determined at 45–50%, 70% and 85% of heart rate reserve (HRR) and maximum velocity. Below 85% HRR no relationship existed between torso shape and running velocity. However, at 85% HRR and, more clearly, at maximum velocity, we found highly statistically significant relations between external torso shape and running performance. Among all trained subjects those with a relatively narrow, flat torso, a small thoracic kyphosis and a more pronounced lumbar lordosis achieved significantly higher running velocities. These results support the hypothesis that external trunk morphology relates to running performance. Low thoracic kyphosis with a flatter ribcage may affect positively respiratory biomechanics, while increased lordosis affects trunk posture and may be beneficial for lower limb biomechanics related to leg return. Assuming that running workload at 45–50% HRR occurs within aerobic metabolism, our results may imply that external torso shape is unrelated to the evolution of endurance running performance.

Air Breathing and Suction Feeding Kinematics in the West African Lungfish, Protopterus annectens.

Research on the water-to-land transition tends to focus on the locomotor changes necessary for terrestriality. However, the evolution from water breathing to air breathing was also a necessary precursor to the invasion of land. Air is approximately 1000 times less dense and 50 times less viscous, and contains hundreds of times more oxygen than water. However, unlike the transition to terrestrial locomotion, breathing air does not require body weight support, so the evolution of air breathing may have necessitated smaller changes to morphology and function. We used X-ray reconstruction of moving morphology to compare the cranial kinematics of aquatic buccal pumping, such as that seen in suction feeding, with the aerial buccal pumping required for lung ventilation in the West African lungfish (Protopterus annectens). During buccal pumping behaviors, the cranial bones and associated soft tissues act as valves and pumps, and the sequence of their motions controls the pattern of fluid flow. Both behaviors are characterized by an anterior-to-posterior wave of expansion and an anterior-to-posterior wave of compression. We found that the pectoral girdle and cranial rib rotate consistently during air breathing and suction feeding, and that the muscle between them shortens during buccal expansion. Overall, we conclude that the major cranial bones maintain the same basic functions (i.e., acting as valves or pumps, or transmitting power) across aquatic and aerial buccal pumping. The cranial morphology that enables aquatic buccal pumping is well suited to perform air breathing and accommodates the physical differences between air and water.

Locomotor activity and spasticity level of the limb in female mice with a spinal cord injury model

Spinal cord injuries (SCI) lead to large-scale physical, physiological, psychological and professional losses. Therefore, today, one of the urgent aims of neurophysiology is the study of the consequences of spinal cord injury. The most common type of SCI is a hemisection. For a comprehensive and detailed study of the functional post-traumatic recovery of the spinal cord, various hemisection options are developed. The aim of the study was to analyse the level of locomotor activity and changes in spasticity of the mice ipsilateral hindlimb (IH) after SCI. Materials and methods. The injury of the left-side spinal cord hemisection was modelled at the level of the lower thoracic segments (T10-T11) in female FVB mice. The locomotor activity and spasticity of the IH were determined every week using the Basso-Beattie-Bresnahan (ВВВ), the Basso (B) scales and the Ashworth scale during the first 1-12 weeks of the post-traumatic period. Results. At a later date (the 11th, 12th weeks) compared with the first weeks of the post-traumatic period, there was a marked recovery of the IH function: 4.39±0.61 points (out of 21 possible) on the BBB scale and 2.22±0.31 points (out of 9 possible) on the B scale. However, at all studied time interval after SCI, a consistently high level of hindlimb spasticity in experimental animals was noted, on the 12th week: 3.03±0.39 (out of 4 possible) on the Ashworth scale. Conclusions. After modelling spinal cord injury by hemisection, spontaneous post-traumatic recovery of locomotor activity was observed (since the 2nd week), which had scores corresponding to the early recovery phase. On the other hand, the levels of IH spasticity in mice were quite high throughout the entire study period, although already at the 2nd week there was a slight decrease in this parameter compared to the 1st week of the post-traumatic period.

Effects of Cannabidiol on Locomotor Activity.

Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest that CBD has anti-inflammatory, analgesic, anxiolytic, antiemetic, anticonvulsant, and antipsychotic properties and influences the sleep–wake cycle. The evaluation of effects on spontaneous motor activity is crucial in experimental pharmacology, and the careful measurement of laboratory animal movement is an established method to recognize the effects of stimulant and depressant drugs. The potential influence of CBD on locomotor activity has been investigated through numerous in vivo experiments. However, there is no clear picture of the impact of CBD on these issues, even though it is administered alone for medical uses and sold with THC as a drug for pain caused by muscle spasms in multiple sclerosis, and it was recently licensed as a drug for severe forms of infantile epilepsy. On this basis, with the aim of developing deeper knowledge of this issue, scientific data on CBD’s influence on locomotor activity are discussed here. We conducted research using PubMed, Scopus, Google Scholar, and a search engine for literature between January 2009 and December 2021 on life sciences and biomedical topics using the keywords “motor activity”, “locomotor activity”, and “locomotion” in combination with “cannabidiol”. In this article, we discuss findings describing the effects on locomotor activity of the CBD precursor cannabidiolic acid and of CBD alone or in combination with THC, together with the effects of CBD on locomotor modifications induced by diseases and on locomotor changes induced by other substances.