Henry Lai - US grants

The applicants propose experiments to further investigate the neural mechanisms involved in the neurological effects of low-level microwave irradiation in the rat. In previous research, the applicants found that acute low-level microwave exposure changed the activity of the cholinergic systems in the rat brain, and after repeated exposure, changes occurred in the muscarinic cholinergic receptors. Furthermore, the applicants found that the effects were mediated by endogenous opioids and corticotropin- releasing factor (CRF) in the brain. To further study the neural mechanisms involved, this proposal has the following objectives: 1) to reveal the subtypes of muscarinic cholinergic receptors (M1 and M2) in the brain affected by low-level microwaves; 2) to investigate the subtypes of endogenous opioid receptors (i.e., mu, delta, and kappa) and the loci in the brain where they mediate the microwave-induced changes in cholinergic activity; and to study the possible changes in opioid receptors in the brain after repeated microwave exposure and 3) to determine the location in the brain where CRF mediates the microwave-induced changes in central cholinergic activity. In addition, since the applicant has also found that low-level microwave irradiation affects spatial learning and memory functions, further experiments are proposed to study the neural mechanisms involved in the learning deficient.

We propose experiments to study the effects of extremely low-frequency (ELF) magnetic field exposure on neurological functions and behavior in the rat. From the data of our preliminary experiments, we hypothesize that acute exposure to ELF magnetic fields activates endogenous opioids, which in turn causes a decrease in cholinergic activity in the brain. These changes in central cholinergic activity lead to a deficit in learning and memory functions. We intend to further investigate and characterize this chain of events through the following experiments: (1) A study to investigate the effects of acute exposure to magnetic fields of different combinations of intensity and duration, and of different frequencies on sodium-dependent high-affinity choline uptake (HACU), an index of cholinergic activity, in different regions of the rat brain. (2) A study to investigate the effects of repeated magnetic field exposure on HACU and muscarinic cholinergic receptors in different regions of the brain. (3) A study to investigate the involvement of opioid receptor subtypes (mu, delta, and kappa) on the effect of magnetic fields on cholinergic systems; and (4) A study to investigate the effect of magnetic field exposure on performance in the radial-arm maze, a behavioral task involving spatial memory functions. Since it is well known that radial-arm maze performance depends on central cholinergic activity, behavioral deficits will be correlated with the changes in cholinergic activity in the brain. It is hoped that the data from these proposed studies will identify the exposure conditions that may trigger deleterious effects, reveal the neural mechanisms affected by ELF magnetic fields, and help in the risk assessment and setting of magnetic field-exposure guidelines in the public and occupational environments.

The applicants propose experiments to further investigate the neural mechanisms involved in the neurological effects of low-level microwave irradiation in the rat. In previous research, the applicants found that acute low-level microwave exposure changed the activity of the cholinergic systems in the rat brain, and after repeated exposure, changes occurred in the muscarinic cholinergic receptors. Furthermore, the applicants found that the effects were mediated by endogenous opioids and corticotropin- releasing factor (CRF) in the brain. To further study the neural mechanisms involved, this proposal has the following objectives: 1) to reveal the subtypes of muscarinic cholinergic receptors (M1 and M2) in the brain affected by low-level microwaves; 2) to investigate the subtypes of endogenous opioid receptors (i.e., mu, delta, and kappa) and the loci in the brain where they mediate the microwave-induced changes in cholinergic activity; and to study the possible changes in opioid receptors in the brain after repeated microwave exposure and 3) to determine the location in the brain where CRF mediates the microwave-induced changes in central cholinergic activity. In addition, since the applicant has also found that low-level microwave irradiation affects spatial learning and memory functions, further experiments are proposed to study the neural mechanisms involved in the learning deficient.

Recent research in our laboratory shows that rats acutely (2 hrs) exposure to a 60-Hz magnetic field (0.1 - 0.5 mT) have an increase in DNA single and double strand breaks in their brain cells. Experiments are proposed to further investigate the mechanism by which exposure to a 60 Hz magnetic field causes DNA damages in brain cells of the rat. Specifically, the role played by free radicals will be investigated, since our preliminary research also shows that treatment of rats before exposure with free radical scavengers (melatonin and a spin trap compound) can block the DNA damaging effect of magnetic fields. Free radicals have recently been implicated in the biological effects of extremely low frequency (ELF) magnetic fields. Experiments are designed to investigate the involvement of free radicals in magnetic field- induced DNA strand breaks in cells. This proposed research has the following specific aims: (1) To further confirm the blocking effect of melatonin on magnetic field-induced DNA single and double strand breaks in brain cells of rats, a (drug) dose-response study will be carried out. (2) To provide further support for the hypothesis that free radicals are involved in the effect of magnetic fields, animals will be treated with different spin-trap compounds and the vitamin E analog trolox to investigate whether they can block the effects of magnetic fields on DNA strand breaks in rat brain cells. Spin-trap compounds and trolox are efficient free radical scavengers. This is an important new direction in ELF electromagnetic field bioeffect research because DNA damage is closely related to human health risk. Particularly, DNA damage in brain cells could affect neurological functions and also possibly lead to carcinogenesis and neurodegenerative diseases. It is hoped that data from this proposed research will help in identifying possible causal connections of exposure to power frequency magnetic fields and biological effects and also in the hazard assessment of power frequency electromagnetic fields.