Horizontal Ambulation Research Articles

Mild burn amplifies the locomotive depression in demyelinated mice without muscle pathophysiological changes.

Patients with mild burns take most accounts, however, the impact of mild burns is less known. Nerve destruction leads to muscle atrophy. We posit that even mild burn injury could worsen demyelinated nerves related to muscle pathophysiological impairment. Young adult C57BL/6 (male, n = 60) mice were randomly fed with either a 0.2% cuprizone diet or a regular rodent diet for 4 weeks. At week 5, all mice were then grouped into mild scald burn with 10% TBSA and sham injury groups. Mice received animal behavior tests and in situ muscle isometric force measurement before euthanasia for tissue collection. Total horizontal ambulation and vertical activity were significantly reduced in mice with mild burn injury (p<0.05). Mice with the cuprizone diet had significantly less time to fall than those with the regular diet on day 7 after burn (p<0.05). No significant difference was found in gastrocnemius tissue weight among the groups, nor muscle isometric tensions (all p>0.05). The cuprizone diet increased the maximal phosphorylating respiration in mice muscle mitochondria (p<0.05). The muscle protein expressions of caspase 3, Fbx-32, and Murf1 significantly increased in mice with the cuprizone diet 3 days after burn (p<0.05). The signal expression of S100B significantly increased in mice with the cuprizone diet, and its expression was even greater on day 7 after burn injury. (p<0.05). The cuprizone diet-induced locomotion and cognitive disorders were amplified by the mild burn injury in mice, which is associated with muscle intracellular signal alterations. However, mild burn injury does not cause mouse muscle weight loss and function impairment. The potential risk of pre-existed neural impairment could be aware when patients encounter even small or mild burns.

Hippocampal expression of aryl hydrocarbon receptor nuclear translocator 2 and neuronal PAS domain protein 4 in a rat model of depression

The transcription factors aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and neuronal PAS domain protein 4 (NPAS4) may influence emotion and cognitive function by regulating brain-derived neurotrophic factor expression in the hippocampus. We estimated hippocampal ARNT2 and NPAS4 expression in chronic unexpected mild stress (CUMS) rat model. The possible association was investigated between expression of these transcription factors and depressive behaviors. Behavioral tests were conducted before, during, and after 28 days of group housing or isolation plus CUMS. The sucrose solution consumption test was used to assess changes in interest and pleasure-seeking, and the open field test (OFT) was conducted to measure spontaneous activity and exploratory behavior. Expression levels of ARNT2 and NPAS4 were estimated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Compared to controls, rats subjected to isolation plus CUMS exhibited significantly reduced weight gain (t = 9.317, P = 0.000), sucrose consumption (t = 3.756, P = 0.003), horizontal ambulation (t = 2.362, P = 0.041), and number of rearings (vertical motion) (t = 2.268, P = 0.040). Relative hippocampal NPAS4 expression was significantly lower in depression model rats compared to controls (t = 2.995, P = 0.010) but there was no significant difference in hippocampal ARNT2 expression between groups (t = 0.091, P = 0.929). The relationship between the CUMS model of depression and NPAS4 expression requires further exploration.

Selective serotonin 5-HT2C receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues

Serotonin (5-HT) controls affective and motivational aspects of palatable food and drug reward and the 5-HT2C receptor (5-HT2CR) has emerged as a key regulator in this regard. We have evaluated the efficacy of a selective 5-HT2CR agonist, WAY 163909, in cocaine and sucrose self-administration and reinstatement assays employing parallel experimental designs in free-fed rats. WAY 163909 dose-dependently reduced the reinforcing efficacy of cocaine (ID50 = 1.19 mg/kg) and sucrose (ID50 = 0.7 mg/kg) as well as reinstatement (ID50 = 0.5 mg/kg) elicited by exposure to cocaine-associated contextual cues, but not sucrose-associated contextual cues. The ID50 of WAY 163909 predicted to decrease the reinforcing efficacy of cocaine or sucrose as well as reinstatement upon exposure to cocaine-associated cues was ∼5–12-fold lower than that predicted to suppress horizontal ambulation (ID50 = 5.89 mg/kg) and ∼2–5-fold lower than that predicted to suppress vertical activity (ID50 = 2.3 mg/kg). Thus, selective stimulation of the 5-HT2CR decreases the reinforcing efficacy of cocaine and sucrose in freely-fed rats, but differentially alters the incentive-salience value of cocaine- vs. sucrose-associated cues at doses that do not impair locomotor activity. Future research is needed to tease apart the precise contribution of 5-HT2CR neurocircuitry in reward and motivation and the learning and memory processes that carry the encoding for associations between environmental cues and consumption of rewarding stimuli. A more complete preclinical evaluation of these questions will ultimately allow educated proof-of-concept trials to test the efficacy of selective 5-HT2CR agonists as adjunctive therapy in chronic health maladies including obesity, eating disorders and drug addiction.This article is part of a Special Issue entitled ‘Serotonin’.

Traction Considerations during Stairway Descent

Investigations of actual pedestrian descent slips on dry stairway-tread nosings indicate that additional analysis of traction requirements during such activity is warranted. Limited bio-mechanical-traction-demand testing utilizing force plates on stairs have been conducted. Results from this work have been used to characterize currently accepted safety factors for stair-tread slip resistance as generous. However, two issues of relevance have not been considered. One is the angle of foot contact with the nosing, which can produce a ramp-effect. Ramp descent necessitates provision of greater slip resistance than does horizontal ambulation. Another is elastomeric friction behavior by shoe heel and -sole materials in contact with treads. in classical metallic theory, the coefficient of friction is directly proportional to the developed frictional resistance force divided by the applied normal load. This is not always so with elastomeric materials. With some elastomers, the friction coefficient decreases as applied normal forces increase. Because of this inverse response, focus widens to include both traction demand by the pedestrian and traction production in the footwear. The potential importance of foot-contact angles and the elastomeric-friction mechanism in stairway descent are assessed.

A STUDY ON BEHAVIORAL, NEUROTOXICOLOGICAL, AND IMMUNOTOXICOLOGICAL EFFECTS OF SUBCHRONIC ARSENIC TREATMENT IN RATS

Male Wistar rats were treated for 4, 8, and 12 wk with 3.33, 6.66, 13.3, or 26.6 mg/kg of inorganic arsenic (NaAsO 2 ) per os by gavage. Changes in behavioral and electrophysiological parameters (spontaneous open-field exploration; electrocorticogram mean frequency and power spectrum; latency and duration of somatosensory, visual, and auditory evoked potentials; conduction velocity; and relative and absolute refractory period of a peripheral nerve) were determined. Treated rats exhibited hypoactivity of horizontal ambulation in the open field and showed depressed rates of grooming. The electrophysiological data, recorded from anesthetized rats, did not show any significant dose- and time-dependent changes. Changes in humoral immune response, tested after 4 wk of treatment, were not marked. The weight of organs responsible for immune response (thymus, spleen, adrenals), was significantly reduced, as were delayed-type hypersensitivity (DTH) reaction and mean cell volume (MCV) of red blood cells a hematological parameter. Plaque-forming cell (PFC) assay proved to be insensitive in this short-time exposure. These results suggest that subchronic low-level exposure to arsenic can affect immune responses and/or spontaneous behavior of rats.

The Neuropeptide Y (NPY) Y1 Receptor Subtype Mediates NPY-induced Antidepressant-like Activity in the Mouse Forced Swimming Test

The present study was undertaken to investigate the possible antidepressant-like effects of neuropeptide Y (NPY) in the mouse forced swimming test, an animal model widely used for the screening of potential antidepressant drugs. In addition, experiments were performed, using agonists and selective antagonists, to assess the potential role of NPY Y1 and Y2 receptor subtypes in this model. Complementary studies were performed in an open field apparatus to rule out any changes in locomotor activity that might have interfered with the interpretation of data from the mouse forced swimming test. Intracerebroventricular injections (0.03 nmole-3 nmole) of NPY, [Leu31Pro34]PYY (Y1 agonist), NPY13-36 (Y2 agonist), BIBP3226, BIBO3304 (Y1 antagonists) and BIIE0246 (Y2 antagonist) were performed 30 min prior to testing in the mouse forced swimming test and open field. NPY administration significantly reduced immobility time in a dose dependent manner (p < .01 vs. control group), as did [Leu31Pro34]PYY (p < .01 vs. control group) and BIIE0246 (p < .05 vs. control group). In contrast, BIBO3304, BIBP3226 and NPY13-36 did not display any activity at the doses tested. However, pretreatment with BIBO3304 or BIBP3226 significantly blocked the anti-immobility effects of NPY. Data from the open field demonstrated that BIIE0246 increased horizontal ambulation at the dose found to be active in the forced swimming test. Taken together, our results demonstrate that NPY displays antidepressant-like activity in the mouse forced swimming test, and suggest that this activity is mediated by the NPY Y1 receptor subtype.

Enhancement of ambulation-increasing effect produced by repeated administration of methamphetamine in rats and neurochemical changes in catecholaminergic neurons.

Male rats of the Wistar strain were repeatedly given methamphetamine (MAP) at 0.5 mg/kg, s.c., 10 times at a fixed interval of 4 days in different environmental situations. The effects of MAP administration on ambulatory activity and neurochemical parameters in the brain were investigated. MAP (0.5 mg/kg) markedly increased ambulatory activity. The ambulation-increasing effect of MAP was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given in the activity cage. The once enhanced effect was considered to be irreversible. In addition, the pretreatment with MAP in the activity cage produced a decrease in the maximum density of 3H-spiperone binding sites in the striatum and that of 3H-WB4101 binding sites in the cortex and hippocampus, with decreases in catecholamine and increases in its metabolites. However, the enhancement of the ambulation-increasing effect of MAP and changes in the binding sites or catecholamine metabolism were scarcely observed when the drug was repeatedly given to the rats in the narrow cage where horizontal ambulation of the animals was strongly impaired. These results suggest that the enhancing effect of MAP is closely related to the environmental situations to which the animals have been exposed to under the drug effect. Moreover, it is indicated that there is a correlation between the enhancement of the ambulation-increasing effect of MAP and changes in the neurochemical parameters. The enhancing effect of MAP is supposed to have been partially caused by changes in cerebral catecholaminergic systems, in particular an increase in catecholamine turnover.

Enhancement of Ambulation-Increasing Effect Produced by Repeated Administration of Methamphetamine in Rats and Neurochemical Changes in Catecholaminergic Neurons

Male rats of the Wistar strain were repeatedly given methamphetamine (MAP) at 0.5 mg/kg, s.c., 10 times at a fixed interval of 4 days in different environmental situations. The effects of MAP administration on ambulatory activity and neurochemical parameters in the brain were investigated. MAP (0.5 mg/kg) markedly increased ambulatory activity. The ambulation-increasing effect of MAP was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given in the activity cage. The once enhanced effect was considered to be irreversible. In addition, the pretreatment with MAP in the activity cage produced a decrease in the maximum density of 3H-spiperone binding sites in the striatum and that of 3H-WB4101 binding sites in the cortex and hippocampus, with decreases in catecholamine and increases in its metabolites. However, the enhancement of the ambulation-increasing effect of MAP and changes in the binding sites or catecholamine metabolism were scarcely observed when the drug was repeatedly given to the rats in the narrow cage where horizontal ambulation of the animals was strongly impaired. These results suggest that the enhancing effect of MAP is closely related to the environmental situations to which the animals have been exposed to under the drug effect. Moreover, it is indicated that there is a correlation between the enhancement of the ambulation-increasing effect of MAP and changes in the neurochemical parameters. The enhancing effect of MAP is supposed to have been partially caused by changes in cerebral catecholaminergic systems, in particular an increase in catecholamine turnover.