In 2014 Biomedical researchers, Hui-Yun Yang, Yang Liu, Jia-Cun Xie, Nan-Nan Liu, and Xin Tian of the School of Biomedical Engineering, Tianjin Medical University, Tianjin, China conducted a research experiment on the effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on vascular dementia. According to the report by Yang et al. (2014) low frequency rTMS is frequently used to treat other illnesses or neurological origin such as depression, parkinson’s disease and epilepsy. The researchers wanted to know if by using rTMS they could protect cells from apoptosis and help maintain plasticity in the hippocampus as well as improving learning and memory. In addition to the observing structural and cognitive changes that rTMS may have on brains with vascular dementia they also observed the effect of rTMS on the concentrations of Bcl-2 and Bax, chemicals associated with apoptosis after rTMS treatment.
For their experiment, the researchers used two month old male rats, which they then divided into three groups. The first group of rats was the control group, which received no bilateral-carotid artery suturing. The other two groups of rats both had their bilateral carotid arteries permanently sutured through the two vessel occlusion model. Once the rats had been given enough time to recover from the surgery they were tested to evaluate their functions to ensure that the motor function of all three groups was about the same. According to the study, there was little difference in the three groups ability to swim, run across a beam, and climb up a pole, meaning that the surgery had had little effect on the rats’ motor functions.
Fourteen days after the rats had undergone surgery, the group designated to receive rTMS treatment in addition to the surgery were administered 1 Hertz of low frequency rTMS to their hippocampuses for 600 seconds every day for a period of 10 days. After this period of time was over, all three rat groups were trained over a period of four days to navigate a Morris Water Maze, which according to the article is a water maze placed in a circular pool, through which the rats must swim to get to the escape platform. Each day for the four days of training, each rat was sent through the maze four times. After the training period was over the rats were all sent through the maze a final time and timed to gauge how quickly they could escape.
The purpose of doing this was to test the rats spatial learning abilities. After the maze tests were complete 3 rats from each group were dissected and had their hippocampal areas studied using electron microscopy and the Western blot method. According the article, the Western blot method is a procedure which uses sodium dodecyl sulfate to separate out various proteins in a sample so that they can be transferred to blotting paper in order to be further identified and studied.
According to Yang et al. the overall findings of the study were that rTMS did improve the learning and spatial memory of the vascular dementia model rats as well as improve their synaptic plasticity. In addition, the rTMS also helped protect the hippocampal cells of the vascular dementia model rats from apoptosis.In the study, this was proved by a variety of tests. First, in the maze test, it was proved beforehand that there was no notable difference in motor function between any of the three rat groups.
The vascular dementia model rats that did not receive low frequency rTMS treatment spent longer in the maze than the vascular dementia model rats that did receive the rTMS treatment, indicating that the rTMS helped them improve their spatial memory. On a cellular level, the improved synaptic plasticity of the hippocampal neurons due to rTMS was proven by electron microscopy when it was found that the rats who received treatment had more, and much less damaged synaptic structures as well as more defined synaptic membrane, compared to the group that did not receive rTMS treatment. According to the article the Western blot test revealed that the rats treated with rTMS had increased levels of Bcl-2 proteins (which inhibits apoptosis) and decreased levels of Bax proteins (which increase apostis).
The Vascular dementia model rats who did not receive treatment showed the opposite results, having an decreased amount of Bcl-2 an increased amount of Bax. The control group came back normal for all the tests. These findings are very significant because they may have impacts of the lives of humans suffering from vascular dementia if this method of treatment is made available for doctors to perform on patients. An important follow-up question to this experiment would be to what other neurological diseases low frequency rTMS may be able to help treat considering it was already proven to help depression, Parkinson’s disease and epilepsy in addition to the effects the experiment suggests rTMS may have on dementia. It may be beneficial to begin conducting similar studies on more rats, pertaining to other neurological diseases to see if the benefits of rTMS extend to those diseases as well.
In addition, a logical next step for the experimenters may be to perform a clinical trial to see if rTMS has any benefits for humans who already have vascular dementia to see if it helps improve their memory or slow hippocampal apoptosis and other dementia related neurological deterioration. In this course there has been significant discussion about the topics of different methodological means of learning about the brain as well as the importance of learning and memory as well as the specific ways in which the brain maintains plasticity and encodes memory.
This article is a good example of howp the methods discussed in the course can be used to study some of the same topics discussed in class like apoptosis, learning and memory as well as neural plasticity. The article also demonstrates how studying these topics are important, not just to further the general knowledge of neuroscience, but in order to help treat serious diseases.