| ObjectiveMild cognitive impairment (MCI) is one transient status between normal aging and dementia, while the definite pathogenesis is still not clear. In this study, to explore the effect of repetitive transcranial magnetic stimulation (rTMS) on rats with MCI, rTMS is applied as a new non-medicine method to delay cognitive declining in MCI.MethodsHeterochronic bilateral common carotid artery occlusion (hBCCAO) was used to make MCI rat models. Morris water-maze test was performed to evaluate the capacity of learning and memory in all involved rats. The electroencephalography (EEG) signals in hippocampal CA1 region were recorded before and after model making and rTMS treatment respectively. The ultrastructure changes of the neurons, especially synapses were observed with transmission electron microscope (TEM).1. AnimalsForty male Wistar rats weighting 280±20g were randomly divided into 4 groups; normal control group, MCI group, LF group, and HLF group.2. MCI rat modelHBCCAO method was used to make MCI rat models. The rats were performed fasting for 8-12h before operation, and applied abdominal anesthesia by 10% chloral hydrate (0.3ml/100g body weight). Fixed the rats lying on the back, selected median incision on abdomen, and performed blunt dissection to expose left common carotid. The artery occlusion was performed by size 4 line. After a week, the same operation was repeated on the right common carotid.3. Repetitive transcranial magnetic stimulationLF rTMS group rats were given 1 Hz rTMS for five weeks; 5 days per week,600 pulses per day; HLF rTMS group rats were given 200 pulse,5 Hz first, and then 600 pulses per day,5 days a week,5 weeks all together.4. Morris water maze test Before Morris water maze test, all rats were given to a free swimming trail without platform to adapt the temperature and environment. The rats that had poor ability of swimming were ticked out of test. During the place navigation test, a hidden platform was placed in the Morris water maze and rats were trained to learn searching for the location of the hidden platform that could be used to escape from swimming. The rats were placed in the maze in different starting position to which were equally distributed around the perimeter of the maze. The trail was lasted for 5 days. The escape latencies were recorded in each group. In the sixth day, a spatial probe test was given, which consisted of a 30-second free swimming period without the platform. Time of crossing the former site of the platform were evaluated statistically.5. Ultrastructure changesIn hippocampal CA1 region, we observed the changes of neurons, especially the synapses with TEM.6. Statistical analysisUse SPSS 13.0 software for statistical disposition. All results were shown by mean±standard deviation. Differences among the three groups were evaluated using one-way ANOVA, and differences between two groups, we used Student's t-test for statistical analysis. P<0.05 was considered as the level of significance.Results1. Morris water maze test resultsThere was no difference among the 4 groups before model making. After model making, the escape latencies in the three model making groups were statistically longer than those in the remained control group(P<0.05), there was no obvious difference among the three model making groups. After rTMS treatment, and the escape latencies in LF rTMS group and HLF rTMS group showed shorter than those in MCI group significantly (P<0.05). The time and distance of crossing the former site of the platform in MCI group were less than those in the two treatment group (P<0.05); LF rTMS group had no statistical difference compared with the HLF group (P>0.05).2. The changes of frequency band power percentage of EEG There was no difference among the 4 groups before MCI model making (P>0.05). After model making operation, compared with the normal control group, the three model making groups had lower alpha-beta band and higher delta-theta band power percentage in EEG (P<0.05). After rTMS treatment, two treatment groups obtained more significant decrease in delta-theta band and increase in alpha-beta band power percentage (P<0.05).3. Ultrastructure changesAfter rTMS treatment, compared with the other two model making groups, the structure of neurons, especially the synapses in MCI group suffered more obvious disorder and damage, while there was no difference among the three model making groups before rTMS. The HLF rTMS group seemed to have less damage than the LF rTMS group.ConclusionsMCI rats have declining ability of learning and memory. It could have a gradually deterioration without any interventions. rTMS can protect the MCI rats from the cognitive function declining. Meanwhile, rTMS can also improve the background of EEG and ultrastructure of the neurons and synapses in hippocampal CA1 region. |
