Extremely low-frequency electromagnetic fields differentially regulate estrogen receptor-α and -β expression in the rat olfactory bulb

Recently, the effects of extremely low-frequency electromagnetic fields (ELF EMF) on biological systems have been extensively investigated. In this report, the influence of ELF EMF on olfactory bulb (OB) estrogen receptor-α (ERα) mRNA and -β (ERβ) mRNA expression was studied by RT-PCR in adult female and male rats. Results reveal for the first time that ELF EMF exerted a biphasic effect on female OB ERβ mRNA gene expression, which increased during diestrous and decreased during estrous. We did not observe any influence of ELF EMF on female OB ERα mRNA expression. Our data demonstrate a fluctuating pattern of ER-α and -β mRNA expression in the female OB throughout the phases of the estrous cycle in non-ELF EMF-exposed animals. Thus the highest ERα expression was observed in diestrous and the lowest in proestrous. The pattern of ERβ mRNA was less variable, the lowest expression was observed in diestrous. ER-α mRNA and -β mRNA expression level in the male OB did not exhibit any variation either in ELF EMF-exposed or non-ELF EMF-exposed animals. In summary, ELF EMF modulate ERβ gene expression in the OB of female adult rats but not in males.     

Vaginocervical stimulation enhances social recognition memory in rats via oxytocin release in the olfactory bulb

The ability of vaginocervical stimulation (VCS) to promote olfactory social recognition memory at different stages of the ovarian cycle was investigated in female rats. A juvenile social recognition paradigm was used and memory retention tested at 30 and 300 min after an adult was exposed to a juvenile during three 4-min trials. Results showed that an intact social recognition memory was present at 30 min in animals with or without VCS and at all stages of the estrus cycle. However, whereas no animals in any stage of the estrus cycle showed retention of the specific recognition memory at 300 min, those in the proestrus/estrus phase that received VCS 10 min before the trial started did. In vivo microdialysis studies showed that there was a significant release of oxytocin after VCS in the olfactory bulb during proestrus. There was also increased oxytocin immunoreactivity within the olfactory bulb after VCS in proestrus animals compared with diestrus ones. Furthermore, when animals received an infusion of an oxytocin antagonist directly into the olfactory bulb, or a systemic administration of alpha or beta noradrenaline-antagonists, they failed to show evidence for maintenance of a selective olfactory recognition memory at 300 min. Animals with vagus or pelvic nerve section also showed no memory retention when tested after 300 min. These results suggest that VCS releases oxytocin in the olfactory bulb to enhance the social recognition memory and that this may be due to modulatory actions on noradrenaline release. The vagus and pelvic nerves are responsible for carrying the information from the pelvic area to the CNS.     

Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition memory

Brief and transient early-life stimulation via neonatal handling and neonatal novelty exposure can lead to differential changes within the right and left brains. In rats, these lateralized changes have been demonstrated behaviorally, neuroanatomically, and neurophysiologically. Recently, we found that neonatal novelty exposure can prolong the duration of social recognition memory from less than 2 hr to at least 24 hr among male rats reared in social isolation and that this enhancement is associated with an initial right-turn preference in a novel testing cage. In contrast to stable forms of asymmetry, such as handedness, we show that this turning asymmetry is dynamic-decreasing as the animal adjusts to the novel testing environment over a 2-day period. This change in turning asymmetry was found only among animals that experienced neonatal novelty exposure during the first 3 weeks of their lives. Furthermore, individual differences in short-term social recognition memory for a conspecific can be predicted by this change in functional asymmetry.     

Short duration of retroactive facilitation of social recognition in rats

Adult rats spent less time investigating the same juvenile during a second dyadic encounter session. This decrease served as an index for social recognition. Social recognition was not influenced by isolating the juveniles for 7 days prior to experimentation. Retroactive facilitation of social recognition was observed when the two rats were confronted for a longer period of time on a given day by multiple testing. However, this facilitation was not observed after a 24-h interexposure interval between encounter sessions, even when different housing conditions during that time were taken into account, and animals were tested during 5 consecutive days. It is suggested that social recognition may be a form of short-term memory.     

Social recognition memory: influence of age, sex, and ovarian hormonal status

Social recognition memory underlies many forms of rodent interaction and can be easily tested in the laboratory. Sex differences in aspects of this memory have been reported among young adults, and some studies indicate an age-related decline among male rats. In contrast, neither the impact of natural fluctuations in ovarian hormones nor the performance of aged female rats on social recognition memory has been previously evaluated. In experiments 1 and 2, the social recognition memory of young adult female Long-Evans rats (age 3-5 months) was compared during proestrus and estrus, and performance was found to be stable across estrous cycle phases. In experiment 3, the social recognition memory of young adults as compared to aged (16.5-19.5 months) rats was tested using the social discrimination procedure, following delays of 15, 45, 90 or 120 min. The estropausal status of aged female rats was tracked during the experiment but was not found to influence memory ability. Males of both ages investigated juveniles (both novel and familiar) more than did females, although despite this difference, both sexes demonstrated robust memory. Interestingly, only young adult females were capable of demonstrating memory following the longest delay. Collectively, our findings indicate that the pattern of age-related changes in social recognition memory is subtle and that aging does not greatly alter the behavioral sex differences observed among young adults.     

Circadian phase and intertrial interval interfere with social recognition memory

A modified version of the social habituation/dis-habituation paradigm was employed to examine social recognition memory in Wistar rats during two opposing (active and inactive) circadian phases, using different intertrial intervals (30 and 60 min). Wheel-running activity was monitored continuously to identify circadian phase. To avoid possible masking effects of the light-dark cycle, the rats were synchronized to a skeleton photoperiod, which allowed testing during different circadian phases under identical lighting conditions. In each trial, an infantile intruder was introduced into an adult's home-cage for a 5-minute interaction session, and social behaviors were registered. Rats were exposed to 5 trials per day for 4 consecutive days: on days 1 and 2, each resident was exposed to the same intruder; on days 3 and 4, each resident was exposed to a different intruder in each trial. The resident's social investigatory behavior was more intense when different intruders were presented compared to repeated presentation of the same intruder, suggesting social recognition memory. This effect was stronger when the rats were tested during the inactive phase and when the intertrial interval was 60 min. These findings suggest that social recognition memory, as evaluated in this modified habituation/dis-habituation paradigm, is influenced by the circadian rhythm phase during which testing is performed, and by intertrial interval.     

N-methyl-D-aspartate improved social recognition potency in rats

Activation of N-methyl-D-aspartate (NMDA) receptors is believed to play an important role in cognitive processes. In the present study we addressed the question of whether systematically administered NMDA can improve social recognition in adult male rats. We utilized the paradigm in which an adult animal is exposed to the same or a novel juvenile during two successive interactions. The adults given NMDA (10, 25 and 50 mg/kg, s.c.) immediately after the initial exposure to a juvenile exhibited significantly reduced social investigation during the second encounter with the same juvenile performed both 120 and 240 min later. Reduction in social investigation was not observed in saline treated animals as well as in those treated with both NMDA and saline but re-exposed to novel juveniles. These results indicate that NMDA improved social recognition potency of adult animals and prolonged retention of previously stored olfactory information.     

Short-term memory in mice is affected by mobile phone radiation

The effects of mobile phone electromagnetic fields (EMFs) were studied on a non-spatial memory task (Object Recognition Task - ORT) that requires entorhinal cortex function. The task was applied to three groups of mice Mus musculus C57BL/6 (exposed, sham-exposed and control) combined with 3 different radiation exposure protocols. In the first protocol designated “acute exposure”, mice 45 days old (PND45 - postnatal day 45) were exposed to mobile phone (MP) radiation (SAR value 0.22 W/kg) during the habituation, the training and the test sessions of the ORT, but not during the 10 min inter-trial interval (ITI) where consolidation of stored object information takes place. On the second protocol designated “chronic exposure-I”, the same mice were exposed for 17 days for 90 min/per day starting at PND55 to the same MP radiation. ORT recognition memory was performed at PND72 with radiation present only during the ITI phase. In the third protocol designated “chronic exposure-II”, mice continued to be exposed daily under the same conditions up to PND86 having received radiation for 31 days. One day later the ORT test was performed without irradiation present in any of the sessions. The ORT-derived discrimination indices in all three exposure protocols revealed a major effect on the “chronic exposure-I” suggesting a possible severe interaction of EMF with the consolidation phase of recognition memory processes. This may imply that the primary EMF target may be the information transfer pathway connecting the entorhinal-parahippocampal regions which participate in the ORT memory task.     

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.     

Prenatal cocaine exposure increases anxiety,impairs cognitive function and increases dendritic spine density in adult rats: influence of sex

Cocaine exposure during pregnancy can impact brain development and have long-term behavioral consequences. The present study examined the lasting consequences of prenatal cocaine (PN-COC) exposure on the performance of cognitive tasks and dendritic spine density in adult male and female rats. From gestational day 8 to 20, dams were treated daily with 30 mg/kg (ip) of cocaine HCl or saline. At 62 days of age, offspring were tested consecutively for anxiety, locomotion, visual memory and spatial memory. PN-COC exposure significantly increased anxiety in both sexes. Object recognition (OR) and placement (OP) tasks were used to assess cognitive function. Behavioral tests consisted of an exploration trial (T1) and a recognition trial (T2) that were separated by an inter-trial delay of varying lengths. Male PN-COC subjects displayed significantly less time investigating new objects or object locations during T2 in both OR and OP tasks. By contrast, female PN-COC subjects exhibited impairments only in OR and only at the longest inter-trial delay interval. In addition, gestational cocaine increased dendritic spine density in the prefrontal cortex and nucleus accumbens in both genders, but only females had increased spine density in the CA1 region of the hippocampus. These data reveal that in-utero exposure to cocaine results in enduring alterations in anxiety, cognitive function and spine density in adulthood. Moreover, cognitive deficits were more profound in males than in females.     

How much are anesthesiologists exposed to electromagnetic fields in operating rooms?

Numerous electronic devices have been introduced into the operating room. Although little is known about the relationship between exposure to electromagnetic fields (EMF) and health hazards, some authors reported its association with cancer or other diseases. We measured the amount of EMF exposure that an anesthesiologist gets in the operating room. The density of the magnetic field was checked by an extremely low frequency (ELF) field strength measurement system in the 19 operating rooms of our hospital. We measured the magnetic field intensity at a distance of 30 cm, 50 cm, and at the place where the anesthesiologist usually stands from the center of the main monitor. The average exposure quantities of magnetic fields in 19 operating rooms were 2.22 +/- 1.13 mG at 30 cm, 1.29 +/- 0.84 mG at 50 cm and 1.00 +/- 0.78 mG at the anesthesiologist's standing points respectively. Because quantities over 2 or 3 mG were accepted to be high radiation levels of EMF by many reports describing the hazards of EMF, we set 2 mG to be the cutoff value. In some of the 19 operating rooms, the measured EMF density exceeded our cutoff value. Although the health hazards related to EMF exposure are still equivocal, anesthesiologists should consider making an effort to improve their environment and reduce their exposure to EMF.     

A review of cancer induction by extremely low frequency electromagnetic fields. Is there a plausible mechanism?

A body of epidemiological evidence suggests an association between residential or occupational exposure to extremely low frequency (ELF) electromagnetic fields (EMF) and an increased incidence of cancer in children and adults. Experimental studies at the whole-animal and cellular level are ambiguous; bioeffects suggestive of a carcinogenic effect have been reported, but a similar volume of negative reports can also be assembled. This literature is critically reviewed based on the hypothesis that the epidemiological results are correct, and asking what plausible mechanism could explain a small increase in the incidence of a range of tumors with a non-specific increased exposure to ELF EMF? We focus on four likely mechanisms: 1) disruption of cell communication, 2) modulation of cell growth via changes in calcium ion flux, 3) activation of specific oncogenic gene sequences, and 4) action as a stress factor operating through disruption of hormonal and immune system tumor control mechanisms. We discuss the implications of epidemiologic and experimental results in the context of hypothetical mechanisms of cancer induction, and suggest experiments likely to help define putative EMF hazards.     

Pathological changes associated with experimental 900-MHz electromagnetic wave exposure in rats

The aim of this study was to determine a possible relationship between whole-body 900-MHz Global System for Mobile Communication-like electromagnetic field (GSM-EMF) exposure and pathological changes in vital organs of Sprague–Dawley rats. Twenty adult male rats were used in four equal independent groups—control (without EMF) and low-, moderate-, and high-exposure groups—according to the time of exposure to EMF (1, 2, and 4 h). The exposure was performed for 30 consecutive days. Tissue samples of the heart, liver, and left kidney were collected and fixed in 10 % buffered formalin for histopathological examination. Some pathological lesions, especially in the kidney (congestion and inflammation) were seen. Our results demonstrate that the use of GSM-like EMF at these intensities and duration can induce pathological lesions in the heart, liver, or kidney, but these are not EMF specific.     

Maternal care affects male and female offspring working memory and stress reactivity

Variations in maternal care affect the development of individual differences in learning and memory and neuroendocrine responses to stress in adult male offspring, but it is not known how variations in maternal care affect adult female offspring. The present study investigated the performance of adult Sprague-Dawley male and female offspring exposed to either low or high levels of maternal licking/grooming on a spatial memory task (Experiment 1) and the effects of acute stress on corticosterone levels and spatial memory performance (Experiment 2). In Experiment 1 rats were trained for 24 days on the spatial working/reference memory version of the radial arm maze (RAM). In Experiment 2, rats were trained on the same RAM task, exposed to an acute stress, and the effect of stress on corticosterone levels and subsequent spatial memory was examined. In Experiment 1, adult female offspring of low licking/grooming dams had enhanced working memory compared to all other groups. In Experiment 2, all groups of male and female offspring had enhanced working memory 24 h after exposure to acute 2 h restraint stress while reference memory was enhanced after stress in male and female offspring of low licking/grooming dams. Furthermore, female offspring of low licking/grooming dams showed the largest corticosterone response to the acute restraint stress compared to all other groups. Male offspring of low licking/grooming dams showed a flattened corticosterone response to stress. Thus variations in maternal care differentially affect working memory and stress reactivity in male and female offspring.     

Impairment of recognition memory and hippocampal long-term potentiation after acute exposure to clioquinol

Clioquinol (CQ) was associated with cases of transient global amnesia and with the neurodegenerative syndrome subacute myelo-optico-neuropathy (SMON) in humans. However, CQ forms lipophilic chelates with cations and has the potential as a scientific and clinical tool used for selective modulation of histochemically reactive zinc pools. The relationship among transient lack of synaptic zinc release, hippocampal long-term potentiation (LTP) induction and cognitive memory is poorly understood. To evaluate the role of synaptic zinc release, in the present study, hippocampal LTP induction and cognitive behavior were examined in young rats after i.p. injection of CQ (30 mg/kg). Intracellular zinc detected by Timm's stain and extracellular (synaptic cleft) zinc detected by ZnAF-2 were significantly decreased in the hippocampus 6 h after CQ injection. The molecular layer of the dentate gyrus, in which perforant path-granule cell synapses exist, was most responsive to CQ injection. Dentate gyrus LTP was induced similarly to the control 2 h after CQ injection, while significantly attenuated 6–24 h after CQ injection. In the training trial of the object recognition memory 2 h after CQ injection, there was no significant difference in learning behavior between the control and CQ-treated rats. In the test trial, CQ-treated rats showed normal recognition memory 1 h after the training, whereas recognition memory deficit 24 h after the training unlike the control rats. These results indicate that acute exposure to CQ impairs long-term (24 h) memory in the hippocampus of young rats. The CQ-mediated attenuation of dentate gyrus LTP, which may be associated with the transient lack of zinc release from zincergic neurons, seems to be involved in the impairment of the long-term memory.     

Modulation of short-term social memory in rats by adenosine A1 and A(2A) receptors

The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. The present study was designed to examine the role of adenosine receptors in the short-term social memory of rats using the social recognition paradigm. Adenosine (5.0-10.0 mg/kg), the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.025-0.05 mg/kg) and the selective adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1.0-5.0 mg/kg), given by i.p. route 30 min before the test, disrupted the juvenile recognition ability of adult rats. This negative effect of adenosine (5.0 mg/kg, i.p.) on social memory was prevented by pretreatment with the non-selective adenosine receptor antagonist caffeine (10.0 mg/kg, i.p.), the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 mg/kg, i.p.) and the adenosine A(2A) antagonist 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, 1.0 mg/kg, i.p.). Furthermore, acute administration of caffeine (10.0-30.0 mg/kg, i.p.), DPCPX (1.0-3.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.) improved the short-term social memory in a specific manner. These results indicate that adenosine modulates the short-term social memory in rats by acting on both A1 and A(2A) receptors, with adenosine receptor agonists and antagonists, respectively, disrupting and enhancing the social memory.     

Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats

The decrease of social investigations of adult rats during a second encounter session with the same juvenile was used as an index of social recognition or memory. Social recognition was present when the interexposure interval was 15 or 30 min, but not when this interval lasted 60 or 120 min. Animals treated with desglycinamide[Arg8]vasopressin (DGAVP) (6.0 micrograms.kg-1, SC) or [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8] (1.0 microgram.kg-1, SC), immediately after the first encounter, recognized the same juveniles still after 120 min, suggesting a facilitatory effect of these peptides on social recognition and that this effect of vasopressin is dissociated from the classical endocrine effects of this hormone. The decrease of social investigating behavior, in both placebo- and DGAVP-treated rats, was completely due to a decrease in anogenital exploration, indicating that the social recognition in rats is presumably based on odor cues from the anogenital part of the body.     

Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase

Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness. Homozygotes evidenced improved performance in spontaneous alternation, an index of immediate spatial working memory; this effect appeared more substantive in males and was reflected in performance in aspects of the Barnes maze, an index of spatial learning/memory. Heterozygotes evidenced impaired performance in object recognition, an index of recognition memory; this effect was evident for both sexes at a retention interval of 5 min but appeared more enduring in males. There were no material effects for either genotype in relation to sociability or social novelty preference. While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. We have reported recently, using similar methods, that mice with deletion of the schizophrenia risk gene neuregulin-1 evidence disruption to social behavior, with little effect on spatial learning/working memory. The data suggest that catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome.     

Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration

It has been demonstrated, in normal and aged rats and mice, that acute i.c.v. ghrelin (Ghr) administration increases memory retention. In order to evaluate if this treatment, restores memory retention in animals exhibiting impaired memory, in the present work we selected a chronic food restriction mouse model (since undernutrition prejudices higher nervous functions). We employed adult female mice with 28 days of 50% food restriction and evaluated: a) behavioral performance using novel object recognition test for memory, and plus maze for anxiety-like behavior, b) some morphometric parameters as body and hepatic weights and c) plasma Ghr levels. The animals with 50% food restriction showed an increase in plasma Ghr levels and a decrease in morphometric parameters and in the percentage of novel object recognition time. When the peptide was i.c.v. injected in food-restricted animals (0.03, 0.3 or 3.0 nmol/microl), memory increases in relation to food-restricted mice injected with vehicle, reaching a performance similar to controls.     

Long-term object location memory in rats: Effects of sample phase and delay length in spontaneous place recognition test

This study investigates the effects of sample phase and delay length on discrimination performance in the spontaneous place recognition (SPR) test in rats. Rats were allowed to explore an arena where two identical objects were presented for 5–20 min (sample phase). After a delay interval, rats were placed again in the same arena but one of the two objects was moved to a novel place (test phase). Results showed that when the sample phase was as long as 20 min, rats preferentially explored the moved object during the test phase even after a 6–24 h delay was interposed. Further sequential and cumulative analyses of the test phase revealed that the preference for the object in a novel place was evident in the first and 2nd min of the test phase in rats with a longer sample phase duration. Correlation analysis showed that locomotor activity and object exploration in the sample phase were not decisive factors in spatial memory performance. The present results demonstrate the importance of the sample phase exposure time and the test phase length.