Andrew J. Parker

A quantitative study of normal locomotion in the rat

Three variables of locomotion; stride length, stride frequency and velocity have been measured in forty-eight rats. Median values were found to be 11.3 cm, 2.4 Hz and 24.2 cm/sec respectively. The results are assessed both as independent variables and in terms of their interaction. It was found that the two variables used to increase velocity (stride length and stride frequency) were not deployed equally during normal walking velocities (10-50 cm/sec). It is proposed that the study of these three readily quantifiable variables, particularly the relationships between velocity and stride frequency may be useful for the evaluation of locomotion in the assessment of neuropharmacologically active agents.

Gait topography in rat locomotion

Gait topography has been quantified and normative data established for free, spontaneous locomotion in rats. The normal walking pattern has been compared for male and female rats and for three rat strains. The normal walking gait was found to be symmetrical, and measures of stride width (SW) and stride length (SL) were consistent, with coefficients of variability ranging between 10 and 21%. A study of gait ontogeny found that for both male and female rats, SL increased as a linear function of body weight, whereas SW increased curvilinearly. The results indicate that repeated measures of gait topography were not subject to interference from habituation. A sex difference in gait ontogeny was observed. The developmental pattern is similar for both sexes, but males increase both SL and SW faster than females. It is proposed that gait topography may yield valuable information in activity studies.

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.

Expression of sulphonylurea receptor protein in mouse kidney

Abstractu2002The sulphonylurea receptor (SUR) is the site of action for sulphonylurea derivatives such as glibenclamide, which are widely used as oral hypoglycaemic agents. Sulphonylureas have also been shown to affect urine flow and salt excretion by the kidney; therefore, the use of these drugs may have important implications for the pharmacological manipulation of renal salt handling. The purpose of the present investigation was to increase our understanding of the possible role of SUR in the regulation of renal function by determining the distribution of SUR isoforms within mouse kidney. Immunostaining with anti-SUR antisera revealed specific staining of SUR2B in distal nephron segments of mouse kidney. A diffuse, low level staining was observed in proximal tubules in the inner cortical region. No evidence was found for the presence of SUR2B in intra-renal blood vessels. Reverse-transcription polymerase chain reaction and Western blotting experiments indicated that SUR2B is the only known isoform expressed. These data demonstrate that SUR2B in mouse kidney is expressed in tubule regions that are critical in determining renal salt excretion.

Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts.

Colonization of the human nasopharynx is a feature of some species of Neisseria, and is a prerequisite of invasive meningococcal disease. The likelihood of colonization by Neisseria meningitidis varies widely between humans, and very few develop invasive disease. Explants of nasal mucosa derived from adult patients with non-allergic nasal obstruction were infected experimentally with Neisseria spp. At intervals over 18 h incubation, washed explants were homogenized, and viable bacteria were counted. To estimate bacterial invasion of mucosa, explants were exposed to 0.25% sodium taurocholate for 30 s prior to homogenization. N. meningitidis was recovered from the mucosa and the organism invaded and replicated within the tissue, in contrast to N. lactamica and N. animalis (n=9, P<0.008). N. meningitidis isolates of clones ET-5, ET-37 and lineage III were recovered from and invaded tissue, but strains of clones A4, A:subgroup I, A:subgroup III and A:subgroup IV-1 did not invade (n=6). To measure host variation, survival of N. meningitidis within nasal mucosa of 40 different human donors was measured. Intra-class correlation of replicates was 0.97, but the coefficient of variation of recovered viable counts was 1335% after 4 h and 77% after 18 h incubation. It is concluded that the distinctive colonization and disease potential of Neisseria spp. may be partly a consequence of their ability to invade and survive within human nasopharyngeal mucosa, but that this is influenced greatly by genetic or environmental factors operating on the host mucosa. This is consistent with the unpredictable epidemiology of meningococcal disease.

Rhinomanometry in the selection for adenoidectomy and its relation to preoperative radiology

Recent work has shown that resolution of otitis media with effusion (OME) following adenoidectomy may be related to certain preoperative radiographic parameters. This study was performed to investigate the relationship between the total nasal resistance (TNR), adenoid volume and the radiographic palatal airway and adenoid depth in children with OME. Fifty-six children underwent anterior active rhinomanometry and 40 completed the investigation. There was a significant association between the Palatal Airway and the TNR, and in the 27 who subsequently underwent adenoidectomy this was nearly so with respect to adenoid volume and TNR. The relationship demonstrated was not strong enough for TNR to be of use in selection of children for adenoidectomy based on radiographic parameters. Rhinomanometry can be difficult and time-consuming to perform in children. In its present form it is unlikely to be of routine clinical use in this context.

Analysis of walking locomotion in adult female rats undernourished as sucklings

Suckling rats were undernourished from birth by underfeeding their mothers. They were refed from 3 weeks of age. Detailed analyses were made of the walking locomotion of previously undernourished and well-fed control female rats at 10 weeks, using electronic, computer, and TV techniques. Previously undernourished rats were found to deploy shorter stride times resulting in greater forward velocities. The shorter stride times were attained by reductions in stance time, while swing time was unaffected. No changes in stride length or width were observed, and the relationships between stride time and velocity, swing, or stance times were unaffected.

Effects of a thyrotropin releasing hormone analogue on locomotor and other motor activity in the rat

In the present experiments, locomotion has been studied in rats after injection of TRH analogue RX77368 (10 mg/kg i.p.). The measure used was the frequency of the cyclic shifts of weight from side to side (WTF) which accompany the progress of locomotion. It therefore provides an indirect measure of stepping frequency. After injection of RX77368 there was a shift in WTFs towards higher frequencies, i.e. when the rat walked it was taking more steps per second. These results suggest that RX77368 stimulates basic motor patterns associated with locomotion. The results obtained in these experiments are compared with those obtained using different quantification methods for locomotion and there is speculation concerning the possible modes of action of RX77368 including interactions with other neurotransmitter systems.

Locomotion in the rat after 5-hydroxy-l-tryptophan

Previous work has shown that administration of 5HTP in amounts substantially less than those required to elicit serotonin syndrome to rats pretreated witha peripheral decarboxylase inhibitor, produced increases in locomotion, measured by whole body movements. The purpose of the present work was to study the cyclic shifts of weights from side to side which underly the progress of locomotion and to see whether these change after 5HTP. From the reciprocal of the interval for one complete cycle was calculated the weight transferral frequency (WTF). The modal WTF for control and treated rats were in the ranges 1-1.49 and 2-2.49 Hz respectively, while the medians were in the ranges 2-2.49 and 2.5-2.99 Hz respectively. Testing of goodness of fit between the frequency distribution curves in control and treated animals showed significant differences. It is concluded that after 5HTP treatment, basic locomotor patterns are shifted towards higher frequencies.

Further studies on the effects of a thyrotropin releasing hormone analogue on locomotor activity in the rat

In these experiments, the relationship between two of the variables of locomotion, stepping frequency and velocity, after injection of the TRH analogue RX77368 (10 mg/Kg i.p.), has been studied. A shift towards higher stepping frequencies was observed, confirming previous observations. However, there was no difference between the velocities of locomotion produced by treated and control rats. In the treated rats the relationship between stepping frequency and velocity was disturbed, such that a higher stepping frequency was employed to attain any particular velocity. This was accompanied by a reduction in stride length. Possible reasons for this disturbance are discussed in terms of changes in muscle stiffness and proprioceptive reflexes.