Cognitive impairment and neural electrophysiological studies in early stage of transgenic Alzheimer's disease mice / 中华行为医学与脑科学杂志

Objective To investigate the early onset of learning and memory function of 4-month-old APP/PS1/Tau Alzheimer' s disease (3×Tg-AD) model mice and explore the pathogenesis of AD in early stage through evaluating neuron excitability and BKCa channel activity in cingulate cortex pyramidal cells.Methods Ten 4-month-old male 3×Tg-AD mice and matched ten wild type (WT) mice.Behavior was tested with the novel object recognition task to observe the ability of learning and memory.Whole-cell patch-clamp recordings were performed to assess the excitability of cingulate cortex pyramidal cells in terms of resting membrane potential and frequencies of spikes evoked by current injection.A train of five pulses of depolarizing currents were injected at 100 Hz to assess the spike width,which was used as an index for BKCa channel activity.Results Compared with the WT group (0.72±0.03),the novel object recognition index significantly decreased in 3 × Tg-AD group (0.55 ± 0.04) (P =0.004).Compared to the WT group((-66.03±0.43) mV),the resting membrane potential in cingulate cortex neurons of 3×Tg-AD group((-62.31±0.54)mV) was significantly depolarized(P=0.000).In contrast to WT group,the action potential firing frequencies evoked by depolarizing current injections were higher in neurons from 3×Tg-AD group(P=0.000),demonstrating that excitability of cingulate cortex neurons was elevated by intracellular Aβ.Spikes were broader in the 3×Tg-AD group than those in the WT group(P＜0.01).Suppression of BKCa channels in cingulate cortex neurons from the 3×Tg-AD group was confirmed on the basis of the spike half-width,since BKCa channels affect the descending phase of spikes.Conclusion Compared to WT mice,4-month-old 3×Tg-AD mice are impaired in learning and memory.The suppression of BKCa channels by intracellular Aβ leads to increase of excitability in cingulate cortex pyramidal cells.

Expression of Hyaluronidase-4 in a Rat Spinal Cord Hemisection Model

STUDY DESIGN: Examination of hyaluronidase-4 (Hyal-4) expression in a rat spinal cord hemisection model. PURPOSE: To determine the status of Hyal-4 expression after hemisection of the spinal cord, and the relationship between its expression and that of chondroitin sulfate proteoglycans (CSPGs). OVERVIEW OF LITERATURE: CSPGs are expressed at the site of spinal cord injury and inhibit axon regeneration. Administration of exogenous chrondroitinase ABC (ChABC), derived from bacteria, digested CSPGs and promoted axonal regrowth. Using a rat hemisection model, we have demonstrated peak CSPGs levels at by 3 weeks after injury but then decreased spontaneously. Could there be an endogenous enzyme similar to ChABC in the spinal cord? It has been suggested that Hyal-4 is involved in CSPG degradation. METHODS: A rat hemisection model was prepared and spinal cord frozen sections were prepared at 4 days and 1, 2, 3, 4, 5, and 6 weeks post-cordotomy and stained for CSPGs and Hyal-4 and subjected to Western blotting. RESULTS: CSPGs appeared at the injury site at 4 days after hemisection, reached a peak after 3 weeks, and then decreased. Hyal-4 was observed around the injury site from 4 days after cordotomy and increased until after 5-6 weeks. Double staining showed Hyal-4 around CSPGs. Western blotting identified a band corresponding to Hyal-4 from 4 days after hemisection. CONCLUSIONS: Hyal-4 was expressed in a rat hemisection model in areas surrounding CSPGs, and as its peak was delayed compared with that of CSPGs. These results suggest the involvement of Hyal-4 in the digestion of CSPGs.

STUDIES ON THE METHOD OF MEASUREMENT OF REPEATED SIDE STEPS / 体力科学

As a method of agility measurement under wide current use, the repeated side step is well-known. At present in Japan, a duration of 20 seconds is employed to test agility ; but it is often reported that the factor of endurance is included in this. When a diagnosis involving agility is made based on the performance of exercise, the duration of the time of measurement was controlled in order to avoid the mixing of other factors and to ensure measurement of as few factors as possible. The distance of step was made flexible according to the age. Since a constant distance makes the longitudinal tracing easier, the distance of step was also studied.<BR>Side steps were tested and duration of measurement was examined based on determinations in 1857 subjects, Junior and Senior school boys and girls and male university students. During the 20 seconds of measurement, scores were recorded every 5 seconds to study the time course of the fluctuations of scores. Taking into consideration factors of endurance such as the endurance of the lower extremity system, the knee test was conducted to see the relationship between scores of the repeated side step and knee test values. As to the distance of the step, 200 high school girls were tested over a distance of 100cm ×2 and 120cm ×2, for 10 seconds each.<BR>As to the time of measurement, the average score during the first 10-15 seconds after start tended to decrease. In the time course of fluctuations of the scores in each subject, a decrease in the fall of scorse was seen about 10 seconds after the start in approximately 55% of the test subjects.<BR>Based on the assumption that the endurance of the lower extremity system participates in this, high and low groups with a significant difference in the endurance of the lower extremity at the level of P<0.001 were compared. While no difference was seen in the slope of the score increase over a 10-second period from the start, changes of scores were distinctly different between 10 and 20 seconds, the lower values in the low group being obvious. The endurance of the lower extremity system was then studied in the two groups with high and low scores in the side step between 10 and 20 seconds. In the group with high scores, the endurance of the lower extremity was high : and a significant difference at P<0.01 was noted in this index.<BR>These results would definitely indicate that mixing of other factors is unavoidable under the current measurement duration of 20 seconds<BR>As to the distance of the step, scores are apparently different even in the same test subject, depending upon the distance of the step. The scores are also different depending upon the body length.<BR>In both of the two groups, however, the scores for each different distance of the step showed a high correlation between each other, giving a correlation coefficient of γ= 0.88 in the group with high body length and γ= 0.82 in the group with low body length, indicating a high correlation.<BR>Based on the diagnosis of agility and performance of exercise, in order to obtain the results of measurement of as simple a factor as possible, the agility time measurement is corrected to 10 seconds ; and the distance of the step is made constant at 100cm×2 regardless of the age, to a distance without unnatural effort even by a primary school pupil, in order to obtain a better diagnosis and tolerance for exercise for the desirable development and maintenance of agility.<BR>The influence of body height on the score should be studied in the future.

A PROPOSAL OF A SIMPLE COMBINATION TEST FOR RELATIVE LOCAL ENDURANCE FOR GENERAL POPULATION / 体力科学

A simple method of evaluation and measurement of endurance of the whole body for exercise prescription for sportsmen was previously reported. In the present study, a method of loading for general population was deviced and is the subject of the present communication.<BR>The site of loading was divided into relatively localized portions of the lower extremity, upper extremity and trunk.<BR>By substituting the kneeling exercise with step test, individual difference in body height was corrected.