Welcome!!
Our research theme is on the effects of environmental chemicals such as pesticides and PM2.5 on the central nervous system (CNS), focusing on the brain immune cells. We are also interested in not only the interaction of chemical exposure and CNS disorders like stroke but also exploring a novel substance which can control neuroimmunity to protect neurons.
We have a space for graduate students. If you are interested in our research, please feel free to contact me (ishiyasu(at)hiroshima-u.ac.jp).
Research Topics
1. Developmental neurotoxicity induced by chemicals
Over 100,000 chemicals are produced and used in medical and industry, but some of them can cause post-growth behavioral disorders due to their fetal and infancy exposure. The effects of these chemicals on the CNS have been focused on the electrical activity and migration of neurons, but much of the mechanism remains unclear. Synapses are over-formed during development, and then are pruned (phagocytosed) by the brain immune cells called microglia. In other words, when microglial activity becomes abnormal (overactivation or suppression) during development, an abnormal neural network could be formed. We have a hypothesis 'Chemicals act on microglia during development to suppress the formation of neural networks, which causes behavioral disorders after growth'. we challenge this hypothesis with in vivo mouse model and in vitro cell culture.
2. Modification of neurological disorders by sustained PM2.5 exporsure
Epidemiological studies have revealed that people living in air-polluted areas have more serious CNS diseases such as ischemic stroke, epilepsy and neurodegenerative diseases than those living in a clear environment. Since the main component of air pollutants is particulate matter typified by PM2.5, it is considered that PM2.5 can affect in the brain and enhance pathological alternation by unkown mechanism. We call this potentiation effects 'PM priming' and challenge to uncover a novel neural action of PM2.5.
3. Neuroprotection by unsaturated fatty acids and its application to prevent neurological disorders
Docosahexaenoic acid (DHA), which is an n-3 highly unsaturated fatty acid contained largely in fish oil, is abundantly present in the brain compared to other tissues. DHA is considered to be an essential molecule for maintaining brain health due to its antioxidative and anti-inflammatory effects. However, the role of DHA in the brain has not been fully elucidated. From the analysis of mice fed with DHA, we found that DHA intake largely increased the amount of a sex steroid, estradiol in the brain. We also revealed that this increase in estradiol was caused by the increased expression of CYP19 and that estradiol suppressed seizures (Ishihara et al. Sci Rep 7: 6268, 2017). Currently, we are investigating whether DHA can be used nutritionally to prevent seizures using febrile seizure model and symptomatic epilepsy model.