Deficits in spatial learning after exposure of mice to a 50 Hz magnetic field

A series of four experiments was performed to determine the effect of exposure to a 50 Hz magnetic field on memory-related behaviour of adult, male C57BL/6J mice. Experimental subjects were exposed to a vertical, sinusoidal magnetic field at 0.75 mT (rms), for 45 min immediately before daily testing sessions on a spatial learning task in an eight-arm radial maze. Control subjects were only exposed to a background time-varying field of less than 50 nT and the ambient static field of about 40 μT. In each experiment, exposure significantly reduced the rate of acquisition of the task but did not affect overall accuracy. This finding is consistent with the results of another study that found that prior exposure to 60 Hz magnetic fields affected spatial learning in rats. Bioelectromagnetics 19:79–84, 1998. © 1998 Wiley-Liss, Inc.     

Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat

In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, β-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat. Bioelectromagnetics 19:432–437, 1998. © 1998 Wiley-Liss, Inc.     

Microwave irradiation affects radial-arm maze performance in the rat

After 45 min of exposure to pulsed 2450 MHz microwaves (2 μsec pulses, 500 pps, 1 mW/cm², average whole body SAR 0.6 W/kg), rats showed retarded learning while performing in the radial-arm maze to obtain food rewards, indicating a deficit in spatial “working memory” function. This behavioral deficit was reversed by pretreatment before exposure with the cholinergic agonist physostigmine or the opiate antagonist naltrexone, whereas pretreatment with the peripheral opiate antagonist naloxone methiodide showed no reversal of effect. These data indicate that both cholinergic and endogenous opioid neurotransmitter systems in the brain are involved in the microwave-induced spatial memory deficit. © 1994 Wiley-Liss, Inc.     

Acute exposure to power-frequency magnetic fields has no effect on the acquisition of a spatial learning task by adult male mice

A series of four experiments was performed to determine whether acute exposure to a range of 50 Hz magnetic fields had any effect on a learning task in adult male CD1 mice. A radial-arm maze placed within the bore of an electromagnet was used to assess spatial discrimination learning for food reward. Subjects were reduced to 85% of their free-feeding weight and were placed in the maze for up to 15 minutes each day for 10 days. Performance of the task was measured by using maximum likelihood techniques to calculate the probability that an animal would not reenter any given arm of the maze. Experimental subjects were exposed to a vertical, 50 Hz sinusoidal magnetic field at 5 μT, 50 μT, 0.5 mT, or 5.0 mT (rms). Control subjects were exposed only to a background time-varying field of less than 50 nT and the ambient static field of about 40 μT. The variation in the applied magnetic field was less than 5% except at the ends of the arms, where it approached 10%. It was found that all eight groups of subjects (n = 10 in all cases) showed similar increases in performance with testing, and the acquisition curve for each group of experimental subjects was not significantly different from that of their control group (P > 0.05 in all cases). It was concluded that exposure had no effect on learning at any flux density. This result is contrary to the findings of a number of preliminary studies, although other studies have reported that magnetic fields do not affect spatial learning in adult male rodents. It is possible that differences between experimental conditions might explain some of this apparent discrepancy. © 1996 Wiley-Liss, Inc.     

磁场对小鼠两种迷宫学习记忆的影响

据发现,磁场对生物体有一定作用,但是磁场对于人类或实验动物的学习记忆是否有影响,目前的报道结果很不一致。本实验采用实验小白鼠,给予不同强度（65高斯／50Hz,35高斯/25Hz）的低频磁场照射（每天1小时,持续25天）。磁场照射后,采用旷场行为测试、Y-迷宫和Morris水迷宫,检测小鼠的活动性、空间辨别、空间学习记忆和非空间学习记忆能力。结果表明：65高斯／50Hz磁场显著增高小鼠的活动性,并损伤小鼠Y-迷宫的空间辨别能力,但对Morris水迷宫的空间、非空间学习记忆无明显影响。35高斯／25Hz磁场处理动物行为在三个指标上均接近对照组。提示：长期的磁场照射可能会给动物,甚至人类造成一些影响。     

50 Hz magnetic field effects on the performance of a spatial learning task by mice

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 μT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 μT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 μT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible. Bioelectromagnetics 19:486–493, 1998. © 1998 Wiley-Liss, Inc.     

灵芝对小鼠空间分辨学习与记忆的影响

本文用Y-型迷宫法测试小鼠空间分辨行为。实验结果表明,每日ig灵芝2.58/kg共7d,有明显促进学习的作用。每日ig灵芝2.5g/kg共7d或ig灵芝5g/kg共7d都能显著地拮坑东莨菪碱所致学习障碍的作用。此外,学习训练后立即ig灵芝2.5g/kg或ig灵芝5g/kg也有明显地改善东莨菪碱损害记忆巩固的作用。     

60 Hz magnetic fields and central cholinergic activity: effects of exposure intensity and duration.

In previous research, we have found that acute exposure to a 60 Hz magnetic field caused a decrease in cholinergic activity in the frontal cortex and hippocampus of the rat. In the present study, the effects of exposure to different intensities of the magnetic field and durations of exposure were investigated. Rats were exposed to a 60 Hz magnetic field for 60 min at a flux density of either 0.5, 1.0, 1.5, or 2.0 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus immediately after exposure to the 2.0 mT field. No significant effect was observed at lower intensities. In another experiment, effect of exposure to a 1.0 mT magnetic field for 30, 45, 60, and 90 min was investigated. A decrease in cholinergic activity was found in both brain areas after 90 min of exposure. No significant effect was observed after shorter durations of exposure. In a further experiment, the exposure duration was extended to 3 h at flux densities of 0.5, 0.1, and 0.05 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus of the rat immediately after exposure to all the intensities. It is concluded that the intensity and duration of exposure interact. By increasing the duration of exposure, effects can be observed at lower intensities.     

Dementia model mice exhibited improvements of neuropsychiatric symptoms as well as cognitive dysfunction with neural cell transplantation

Elderly patients with dementia suffer from cognitive dysfunctions and neuropsychiatric symptoms (NPS) such as anxiety and depression. Alzheimer’s disease (AD) is a form of age-related dementia, and loss of cholinergic neurons is intimately associated with development of AD symptoms. We and others have reported that neural cell transplantation ameliorated cognitive dysfunction in AD model mice. It remains largely unclear whether neural cell transplantation ameliorates the NPS of AD. It would be interesting to determine whether NPS correlates with cognitive dysfunctions before and after neural cell transplantation in AD model mice. Based on the revalidation of our previous data from a Morris water maze test, we found that neural cell transplantation improved anxiety and depression significantly and marginally affected locomotion activity in AD mice. A correlation analysis revealed that the spatial learning function of AD mice was correlated with their NPS scores both before and after cell transplantation in a similar manner. In contrast, in the mice subjected to cell transplantation, spatial reference memory function was not correlated with NPS scores. These results suggested the neural cell transplantation in the AD model mice significantly improved NPS to the same degree as cognitive dysfunctions, possibly via distinct mechanisms, such as the cholinergic and GABAergic systems.     

Acute exposure to a 60 Hz magnetic field affects rats' water-maze performance

Rats were trained in six sessions to locate a submerged platform in a circular water-maze. They were exposed to a 1 mT, 60 Hz magnetic field for one hour in a Helmholtz coil system immediately before each training session. In addition, one hour after the last training session, they were tested in a probe trial during which the platform was removed and the time spent in the quadrant of the maze in which the platform was located during the training sessions was scored. Control animals were sham-exposed using the exposure system operating with the coils activated in an anti-parallel direction to cancel the fields. A group of “non-exposed” control animals was also included in the study. There was no significant difference between the magnetic field-exposed and control animals in learning to locate the platform. However, swim speed of the magnetic field-exposed rats was significantly slower than that of the controls. During the probe trial, magnetic field-exposed animals spent significantly less time in the quadrant that contained the platform, and their swim patterns were different from those of the controls. These results indicate that magnetic field exposure causes a deficit in spatial “reference” memory in the rat. Rats subjected to magnetic field exposure probably used a different behavioral strategy in learning the maze. Bioelectromagnetics 19: 117–122, 1998. © 1998 Wiley-Liss, Inc.     

Variable spatial magnetic field influences peripheral nerves regeneration in rats

Generator of spatial magnetic field is one of most recent achievements among the magnetostimulators. This apparatus allows to obtain the rotating magnetic field. This new method may be more effective than other widely used techniques of magnetostimulation and magnetotherapy. We investigated the influence of alternating, spatial magnetic field on the regeneration of the crushed rat sciatic nerves. Functional and morphological evaluations were used. After crush injury of the right sciatic nerve, Wistar C rats (n?=?80) were randomly divided into four groups (control and three experimental). The experimental groups (A, B, C) were exposed (20?min/day, 5?d/week, 4 weeks) to alternating spatial magnetic field of three different intensities. Sciatic Functional Index (SFI) and tensometric assessments were performed every week after nerve crush. Forty-eight hours before the sacrificing of animals, DiI (1,1’-di-octadecyl-3,3,3’,3’-tetramethyloindocarbocyanine perchlorate) was applied 5?mm distally to the crush site. Collected nerves and dorsal root ganglia (DRG) were subjected to histological and immunohistochemical staining. The survival rate of DRG neurons was estimated. Regrowth and myelination of the nerves was examined. The results of SFI and tensometric assessment showed improvement in all experimental groups as compared to control, with best outcome observed in group C, exposed to the strongest magnetic field. In addition, DRG survival rate and nerve regeneration intensity were significantly higher in the C group. Above results indicate that strong spatial alternating magnetic field exerts positive effect on peripheral nerve regeneration and its application could be taken under consideration in the therapy of injured peripheral nerves.     

Effect of the magnetic field curvature on magnetic islands in tokamaks

The effect of the magnetic field curvature on magnetic islands in a tokamak is analyzed. It is demonstrated that the original investigation of this effect by Kotschenreuther et al. (1985) is inconsistent: on the one hand, the authors made the correct assumption that this is an ideal effect and, on the other hand, they described it in terms of the parameters characteristic of the “resistive ordering” approach, which is incompatible with the ideal approximation. More recent studies of the magnetic curvature effect have produced further ambiguities; as a result, a branch of the theory of magnetic islands has arisen that is based on the supposition that the effect under discussion can be described in terms of the Glasser-Greene-Johnson parameter D_R. This branch is shown to be erroneous, because the parameter D_R describes the plasma response to magnetic field perturbations on spatial scales of about the dimension of the linear resistive layer, while the characteristic spatial scale of the magnetic islands is much longer. It is concluded that the correct theory developed here for the magnetic curvature effect makes more optimistic predictions about its stabilizing role.     

Lesions of the Basal Forebrain Cholinergic System in Mice Disrupt Idiothetic Navigation

Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer’s disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer’s disease patients perform poorly on both real space and computerized cued (allothetic) or uncued (idiothetic) recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze), and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer’s disease.     

Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 μg), CEE-Medium (20 μg) or CEE-High (30 μg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 β-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.     

A novel strategy of selective gene delivery by using a uniform magnetic field

The application of a magnetic field to enhance the transfection efficiency has been reported to be mainly dependent on the magnetic force generated by a magnetic field gradient to attract paramagnetic bead-conjugated carrier and polynucleotide complexes. This strategy has the advantage of targeting a point or an area on the culture vessel. However, it is difficult to target deeply placed tissues in vivo. Uniform magnetic field-correlated effect is applicable to such a purpose. Here, we attempted to establish a novel procedure for uniform magnetic field-dependent enhancement of transfection efficiency. We examined the effect of a 1.5 mT uniform magnetic field on cellular reactive oxygen species (ROS) level and transfection efficiency mediated by a ROS-sensitive transfection carrier. Our experimental results revealed that a 1.5 mT uniform magnetic field transiently decreased cellular ROS levels and strongly enhanced transfection efficiency mediated by polyethylenimine (PEI). The uniform magnetic field-dependent enhancement of PEI-mediated in vivo transfection was confirmed in the livers of mice. Local intensification of a uniform magnetic field in a culture dish resulted in selective gene delivery into cells on the target area. Although further examination and improvement are necessary for this procedure, our findings provide a novel option for spatial control of gene delivery.     

Nerve Growth Factor Differentially Affects Spatial and Recognition Memory in Aged Rats

In rats, object discrimination depends on the integrity of the cholinergic system, thus it could be expected that nerve growth factor (NGF) can improve the behavior in aged subjects. The interactive effect of age and cholinergic improvement was assessed behaviorally in young and aged rats. Animals were injected by infusion of NGF into the lateral ventricles and they were tested in two behavioral tasks: an object-location and an object-recognition task. Spatial and recognition memory were assessed in an open field containing five different objects. Rats were submitted to six consecutive sessions. Both age-groups showed comparable habituation of exploratory response in Session 1–4. Discrimination index (DI) was calculated to assess responses to spatial change in Session 5 and object change in Session 6. Control young and aged rats were able to discriminate between familiar and novel object, however DI was lower in aged rats. Treatment with NGF induced decline of object discrimination in both age-groups. Different results were obtained in spatial displacement test. NGF was able to improve spatial memory in aged rats, but had no effect in young controls. These data confer on NGF potential role in improving spatial but not episodic memory in aged rats.     

Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections

This study examined whether effects on turning strategy, use of an allocentric strategy, and/or short-term spatial memory account for the effects of estradiol treatment on acquisition of a delayed matching-to-position (DMP) T-maze task, in rats with and without basal forebrain cholinergic lesions. Ovariectomized rats received either 192IgG saporin (SAP) or saline injected into the medial septum. Two weeks later, half of each group received either continuous estradiol treatment (5-mm silastic capsule containing 17-beta-estradiol implanted s.c.) or implantation of an empty capsule. All rats were trained on the DMP task. Results show that estradiol enhanced, and SAP lesions impaired, learning on the DMP task. SAP lesions impaired learning primarily by increasing the use of a persistent turning strategy early on during training. In contrast, estradiol had no apparent effect on turning strategy, and enhanced learning only in non-lesioned rats. There was no evidence that any of these effects were due primarily to an effect on ultimate strategy selection (e.g., allocentric vs. egocentric, evaluated with a probe trial in which the maze was rotated 180 degrees), or on short-term spatial memory (evaluated by increasing the intertrial delay). We conclude that estradiol enhances DMP acquisition via a mechanism independent of effects on turning strategy and short-term memory, but nevertheless dependent on cholinergic neurons in the MS and VDB. We hypothesize that estradiol may affect the facility with which female rats are able to extract and incorporate extramaze information into an effective navigational strategy, and that this may be mediated by effects in prefrontal cortex.     

Effects of vinconate on spatial learning impairments induced by medial septal lesion in rats.

We investigated the effects of vinconate, a novel vinca alkaloid, on spatial learning deficits induced by medial septal (MS) lesion in rats. MS lesion was produced by passing an anodal DC current. In vehicle-treated MS-lesioned rats impairment of spatial learning was observed, shown by a decrease in correct choices and an increase in total errors during training in a radial arm maze task. Vinconate (10 mg/kg) treatment alleviated the decrease in correct choices and the increase in total errors induced by MS lesion. Vinconate (5 and 10 mg/kg) treatment showed a tendency to reverse the decrease in choline acetyltransferase activity in the hippocampus caused by MS lesion. The present study suggests that vinconate has an anti-amnesic effect on MS lesion-induced amnesia by ameliorating the dysfunction in cholinergic (ACh) neurons.     

静磁场保健寝具磁参数的评价

基于对生物磁学效应的研究,磁疗成为替代医学和补充医学的一种有效的治疗方法,本文通过对现有静磁场（恒定磁场）保健寝具磁标准和磁剂量的评述,首次提出磁保健寝具三围空间磁场的概念,指出采用磁感应强度在空间的强度分布作为磁保健剂量标准。论述了三围空间磁场具体磁参数的评价,包括所用磁源的表面磁感应强度,寝具织物表面磁场的穿透力、梯度、有效磁通量和空间能量等磁场分布的描述性指标。指出了静磁场保健寝具磁参数的合理的评价参量：为确保织物表面磁感应强度在目前认知的400～1100Gs有效安全剂量内,依据使用时的织物厚度,磁保健寝具选用的磁体表磁应在1000-3000Gs左右．且磁场的梯度不宜过大,磁场的平均穿透力在25-30cm左右,以确保空间磁场能量的有效作用于人体深处。     

Germination of soybean seeds exposed to the static/alternating magnetic field and algal extract

In the present study, the effect of the static and alternating magnetic field applied individually and in combination with an algal extract on the germination of soybean seeds (Glycine max (L.) Merrill) and chlorophyll content was examined. The exposure time of seeds to the static magnetic field was 3, 6, and 12 min, whereas to the alternating magnetic field was 1, 2.5, and 5 min. The static magnetic field was obtained by means of a permanent magnets system while the alternating magnetic field by means of magnetic coils. Algal extract was produced from a freshwater macroalga—Cladophora glomerata using ultrasound homogenizer. In the germination tests, 10% extract was applied to the paper substrate before sowing. This is the first study that compares the germination of soybean seeds exposed to the static and alternating magnetic field. The best effect on the germination and chlorophyll content in seedlings had synergistic action of the static magnetic field on seeds for 3 min applied together with the extract and alternating magnetic field used for 2.5 min. It is not possible to clearly state which magnetic field better stimulated the germination of seeds, but the chlorophyll content in seedlings was much higher for alternating magnetic field.