Background. This study was undertaken to determine (a) whether a program of regular exercise can improve gait patterns in older women, and (b) whether any such improvement in gait is mediated by ...increased lower limb muscle strength. Method. A 22-week randomized controlled trial of exercise was conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. Subjects were 160 women aged 60–83 years (Mean age 71.1, SD = 5.2) who were randomly recruited from the community. Exercise and control subjects were tested prior to and at the end of the trial. At initial testing, exercisers and controls performed similarly in the strength and gait parameters. They were well matched in terms of age and a number of health and life-style characteristics. Results. At the end of the trial, the exercise subjects showed improved strength in five lower limb muscle groups, increased walking speed, cadence, stride length, and shorter stride times as indicated by both reduced swing and stance duration. There were no significant improvements in any of the strength or gait parameters in the controls. Within the exercise group, increased cadence was associated with improved ankle dorsiflexion strength, and increased stride length was associated with improved hip extension strength. Exercise subjects with initial slow walking speed showed greater changes in velocity, stride length, cadence, and stance duration than those with initial fast walking speed. Conclusion. These findings show that exercise can increase gait velocity and related parameters in older persons, and that part of this increase may be mediated by improved lower limb muscle strength.
The localization of neurons expressing mRNAs for the NRI and NR2A‐D subunits of the glutamatergic NMDA receptor was examined by non‐radioactive in situ hybridization throughout the guinea pig ...vestibular nuclei. After deafferentation of the vestibular nuclei by unilateral labyrinthectomy, modifications of the mRNA distributions were followed for 30 days. A quantitative analysis was performed in the medial vestibular nucleus by comparison of the labelled neurons in the ipsi‐ and contra‐lateral nuclei. In vestibular nuclei, the NR1 subunit mRNA was found in various populations of neurons. The NR2A and NR2C subunit mRNAs were less widely distributed, whereas little NR2D mRNA was detected and only rare cells contained NR2B mRNA. NRI and NR2A‐D mRNAs were colocalized in some but not other neuronal types. Twenty hours after the lesion, there was a transient ipsilateral increase of NR1 mRNA level in the medial vestibular nucleus, followed by a decrease 48 h after the lesion and, at 3 days, by recovery to the control level. An ipsilateral increase in the mRNA level of NR2C subunit was detected 20 h after lesion and maintained at 48 h. No significant changes were apparent in NR2A, NR2B and NR2D mRNA levels. The distributions and the differential signal intensities of NR2A‐D mRNAs suggest various subunit organizations of the NMDA receptors in different neurons of the vestibular nuclei. Neuronal plasticity reorganizations in the vestibular nuclei following unilateral labyrinthectomy appear to include only changes in NR1 and NR2C mRNA levels modifying the functional diversity of the NMDA receptor in the ipsilateral medial vestibular nucleus neurons. The transient changes in NRI and the NR2C subunit mRNA expressions in response to sensory deprivation are consistent with an active role for NMDA receptors in the appearance and development of the vestibular compensatory process.
Space flight produces changes in neuronal activity in the vestibular system. We studied the protein expression of the NMDA receptor subunit NR1 in the vestibular ganglia of rats exposed to ...microgravity for 17 days, beginning on postnatal day 8, as part of the NASA Neurolab mission. As a control, we studied the cochlear ganglia in the same way. NR1 expression in rats that had experienced microgravity (flight-FLT rats) was compared with that in two types of ground control. One control consisted of rats housed in regular cage conditions (VIV, vivarium); the other, asynchronous ground control (AGC), consisted of rats kept in cages similar to those used in flight (animal enclosure module, AEM), requiring no human care. After 8 days of flight, NR1 levels in the vestibular and cochlear neurons were similar in FLT, VIV and AGC rats. In contrast, 8 h after landing, the FLT and VIV animals showed similar, normal levels of NR1 staining, whereas the ganglia of the AGC animals displayed only very faint staining. Thus, microgravity did not modify NR1 expression in vestibular neurons. The lower levels of NR1 expression in the vestibular and cochlear neurons of AGC rats suggest an effect of confinement for 17 days in AEMs on the ground.
The postnatal developmental expression and the distribution of the glutamate transporters (GLAST, GLT-1 and EAAC1) were analyzed in rat vestibular nuclei (VN), at birth and during the following 4 ...weeks. Analyses were performed using reverse transcriptase-polymerase chain reaction and immunoblotting of GLAST, GLT-1 and EAAC1 mRNA and protein during the postnatal development of the VN neurons and their afferent connections. We also studied the distribution of each glutamate transporter in the medial and lateral VN by use of immunocytochemistry and confocal microscopy. GLAST, GLT-1 and EAAC1 mRNA and protein were present in the VN at each developmental stage. GLAST was highly expressed mainly in glia from birth to the adult stage, its distribution pattern was heterogeneous depending on the region of the medial and lateral VN. GLT-1 expression increased dramatically during the second and third postnatal weeks. At least during the first postnatal week, GLT-1 was expressed in the soma of neurons. EAAC1 was detected in neurons and decreased from the third week. These temporal and regional patterns of GLAST, GLT-1 and EAAC1 suggest that they play different roles in the maturation of glutamatergic synaptic transmission in the medial and lateral VN during postnatal development.
The presence and the activity of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) glutamate receptors were investigated in mouse cultured vestibular ganglion neurons using ...immunocytochemistry and measurement of intracellular calcium concentration (Ca2+,) by spectrofluorimetry. Cultures of dissociated vestibular ganglia from 18 gestation day mouse embryos were grown in vitro for 3–4 days. lmmunocytochemical labelling of AMPA receptor subunits GluR2/R3 and GluR4 was detected in neuron cell bodies and proximal neurites and more lightly in glial cells. There was no clear selective subcellular localization of the different subunits. For the GluR1 subunit a signal was observed only in some neurons and neurites and was weak. Vestibular ganglion neurons responded to fast application of 1 mM glutamate and 10 mM aspartate through unknown receptors by a transient increase in Ca2+i. The mean amplitude of this rapid increase was about nine times the resting level and recovery was complete within 30–45 s after the application. If separated by an interval of at least 10 min, consecutive applications produced similar calcium responses. AMPA (1 mM) application induced the same type of responses. Five minutes prior to the AMPA exposure, the application of a specific AMPA antagonist, 6, 7‐dinitroquinoxaline‐2, 3‐dione (DNQX, 1.5 mM), in the external medium inhibited the response to AMPA. Chelation of external calcium by EGTA (1.5 mM) abolished the responses to drug applications, indicating that an influx of external calcium is involved in the Ca2+i increase. These observations suggest that heteromeric AMPA receptors are expressed in vestibular ganglion neurons in culture and play a functional role in their glutamate‐induced depolarization. Experiments are in progress using specific AMPA and NMDA antagonists to characterize the participation of the two types of ionotropic glutamate receptors in the glutarnate/aspartate‐induced intracellular calcium response.