Hippocampal ferroptosis is involved in learning and memory impairment in rats induced by microwave and electromagnetic pulse combined exposure.

Microwave (MW) and electromagnetic pulse (EMP) are considered environmental pollutants, both of which can induce learning and memory impairments. However, the bioeffects of combined exposure to MW and EMP have never been explored. This paper aimed to investigate the effects of combined exposure to MW and EMP on the learning and memory of rats as well as its association with ferroptosis in the hippocampus. In this study, rats were exposed to EMP, MW, or EMP and MW combined radiation. After exposure, impairment of learning and memory, alterations in brain electrophysiological activity, and damage to hippocampal neurons were observed in rats. Moreover, we also found alterations in ferroptosis hallmarks, including increased levels of iron, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, as well as downregulation of glutathione peroxidase 4 (GPX4) protein in the rat hippocampus after exposure. Our results suggested that either single or combined exposure to MW and EMP radiation could impair learning and memory and damage hippocampal neurons in rats. Moreover, the adverse effects caused by the combined exposure were more severe than the single exposures, which might be due to cumulative effects rather than synergistic effects. Furthermore, ferroptosis in the hippocampus might be a common underlying mechanism of learning and memory impairment induced by both single and combined MW and EMP exposure.

Possible effects of different doses of 2.1 GHz electromagnetic radiation on learning, and hippocampal levels of cholinergic biomarkers in Wistar rats.

The present study evaluated whether short-term exposure to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) has different effects on rats' behaviour and hippocampal levels of central cholinergic biomarkers. Animals were divided into three equal groups namely; group 1 was sham-exposed group, group 2-3 were exposed to 45 V/m and 65 V/m doses of 2.1 GHz frequency for 1 week respectively. Numerical dosimetry simulations were carried out. Object location and Y-maze were used as behavioural tasks. The protein and mRNA expression levels of AChE, ChAT, and VAChT, in the hippocampus were tested using Western Blotting and Real-Time PCR. The impairment performance of rats subjected to 65 V/m dose of 2.1 GHz RF-EMR in both object location and Y-maze tasks was observed. The hippocampal levels of AChE, ChAT, and VAChT, were significantly lower in rats exposed to 65 V/m dose of 2.1 GHz RF-EMR than others. The stronger effect of "65 V/m" dose on both rat's hippocampal-dependent behavioural performances and hippocampal levels of cholinergic biomarkers may be due to the stronger effect of "65 V/m" dose where rats' snouts were located at the nearest distance from the monopole antenna. Furthermore, the simulated SAR values were high for 65 V/m electric-field strengths. For the first time, we report the potential dose-dependent effects of short-term exposure to 2.1 GHz radiation on rat's behavioural performances as well as hippocampal levels of cholinergic biomarkers. Further studies are needed to understand the mechanisms by which RF-EMR influences the function of the central cholinergic system in the brain.

Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects.

Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.

Cue-Evoked Dopamine Neuron Activity Helps Maintain but Does Not Encode Expected Value.

Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value, but its influence on reward assessment is unclear. In mice performing a trial-based operant task, we test if bidirectional manipulations of cue or operant-associated DA neuron activity drive learning as a result of under- or overexpectation of reward value. We target optogenetic manipulations to different components of forced trials, when only one lever is presented, and assess lever biases on choice trials in the absence of photomanipulation. Although lever biases are demonstrated to be flexible and sensitive to changes in expected value, augmentation of cue or operant-associated DA signaling does not significantly alter choice behavior, and blunting DA signaling during any component of the forced trials reduces choice trial responses on the associated lever. These data suggest cue-evoked DA helps maintain cue-value associations but does not encode expected value as to set the benchmark against which received reward is judged.

Single session high definition transcranial direct current stimulation to the cerebellum does not impact higher cognitive function.

The prefrontal cortex is central to higher order cognitive function. However, the cerebellum, generally thought to be involved in motor control and learning, has also been implicated in higher order cognition. Recent work using transcranial direct current stimulation (tDCS) provides some support for right cerebellar involvement in higher order cognition, though the results are mixed, and often contradictory. Here, we used cathodal high definition tDCS (HD-tDCS) over the right cerebellum to assess the impact of HD-tDCS on modulating cognitive performance. We predicted that stimulation would result in performance decreases, which would suggest that optimal cerebellar function is necessary for cognitive performance, much like the prefrontal cortex. That is, it is not simply a structure that lends support to complete difficult tasks. While the expected cognitive behavioral effects were present, we did not find effects of stimulation. This has broad implications for cerebellar tDCS research, particularly for those who are interested in using HD-tDCS as a way of examining cerebellar function. Further implications, limitations, and future directions are discussed with particular emphasis on why null findings might be critical in developing a clear picture of the effects of tDCS on the cerebellum.

Early-Life Exposure to Pulsed LTE Radiofrequency Fields Causes Persistent Changes in Activity and Behavior in C57BL/6 J Mice.

Despite much research, gaps remain in knowledge about the potential health effects of exposure to radiofrequency (RF) fields. This study investigated the effects of early-life exposure to pulsed long term evolution (LTE) 1,846 MHz downlink signals on innate mouse behavior. Animals were exposed for 30 min/day, 5 days/week at a whole-body average specific energy absorption rate (SAR) of 0.5 or 1 W/kg from late pregnancy (gestation day 13.5) to weaning (postnatal day 21). A behavioral tracking system measured locomotor, drinking, and feeding behavior in the home cage from 12 to 28 weeks of age. The exposure caused significant effects on both appetitive behaviors and activity of offspring that depended on the SAR. Compared with sham-exposed controls, exposure at 0.5 W/kg significantly decreased drinking frequency (P ≤ 0.000) and significantly decreased distance moved (P ≤ 0.001). In contrast, exposure at 1 W/kg significantly increased drinking frequency (P ≤ 0.001) and significantly increased moving duration (P ≤ 0.005). In the absence of other plausible explanations, it is concluded that repeated exposure to low-level RF fields in early life may have a persistent and long-term effect on adult behavior. Bioelectromagnetics. 2019;40:498-511. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.

Mobile phone induced cognitive and neurochemical consequences.

With the rapid advances in technology, extensive use of mobile phones has increased the risk of health problems. This study was performed to find out the effect of mobile phone frequency on male Wistar rats. Animals were divided into two groups (n = 6 in each group). Group one was considered as control and group two (experimental group) was exposed to microwave radiation (2100 MHz) for 4 hours/day (5 days/week) for 3 months. Exposure of microwave radiation frequency showed significant alterations in cholinesterase activity, muscular strength, learning ability and anxiety. MWR exposure was also associated with significant alteration in the oxidative defense system and hippocampus degeneration. Histopathological observations clearly depicted the neural degeneration. Thus, it can be concluded that MWR significantly affects the central nervous system and may lead to many severe illnesses. This study may reveal a platform to understand its toxic effect and can further be used for amendment in current guidelines of mobile radiation.

Radiofrequency electromagnetic radiation-induced behavioral changes and their possible basis.

The primary objective of mobile phone technology is to achieve communication with any person at any place and time. In the modern era, it is impossible to ignore the usefulness of mobile phone technology in cases of emergency as many lives have been saved. However, the biological effects they may have on humans and other animals have been largely ignored and not been evaluated comprehensively. One of the reasons for this is the speedy uncontrollable growth of this technology which has surpassed our researching ability. Initiated with the first generation, the mobile telephony currently reaches to its fifth generation without being screened extensively for any biological effects that they may have on humans or on other animals. Mounting evidences suggest possible non-thermal biological effects of radiofrequency electromagnetic radiation (RF-EMR) on brain and behavior. Behavioral studies have particularly concentrated on the effects of RF-EMR on learning, memory, anxiety, and locomotion. The literature analysis on behavioral effects of RF-EMR demonstrates complex picture with conflicting observations. Nonetheless, numerous reports suggest a possible behavioral effect of RF-EMR. The scientific findings about this issue are presented in the current review. The possible neural and molecular mechanisms for the behavioral effects have been proposed in the light of available evidences from the literature.

Space-like 56Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer's-like transgenic mice.

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer's disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was reduced in female mice independently of cerebral blood flow. Biochemical and immunohistochemical analyses revealed that radiation reduced cerebral amyloid-ß levels and microglia activation in female Tg mice, modestly increased microhemorrhages in 50 cGy irradiated male WT mice, and did not affect synaptic marker levels compared to sham controls. Taken together, we show specific short-term changes in neuropathology and behaviour induced by 56Fe irradiation, possibly having implications for long-term space travel.

iTRAQ quantitatively proteomic analysis of the hippocampus in a rat model of accumulative microwave-induced cognitive impairment.

Central nervous system is sensitive and vulnerable to microwave radiation. Numerous studies have reported that microwave could damage cognitive functions, such as impairment of learning and memory ability. However, the biological effects and mechanisms of accumulative microwave radiation on cognitive functions were remained unexplored. In this study, we analyzed differential expressed proteins in rat models of microwave-induced cognitive impairment by iTRAQ high-resolution proteomic method. Rats were exposed to 2.856 GHz microwave (S band), followed by 1.5 GHz microwave exposure (L band) both at an average power density of 10 mW/cm2 (SL10 group). Sham-exposed (control group), 2.856 GHz microwave-exposed (S10 group), or 1.5 GHz microwave-exposed (L10 group) rats were used as controls. Hippocampus was isolated, and total proteins were extracted at 7 days after exposure, for screening differential expressed proteins. We found that accumulative microwave exposure induced 391 differential expressed proteins, including 9 downregulated and 382 upregulated proteins. The results of GO analysis suggested that the biological processes of these proteins were related to the adhesion, translation, brain development, learning and memory, neurogenesis, and so on. The cellular components mainly focused on the extracellular exosome, membrane, and mitochondria. The molecular function contained the protein complex binding, protein binding, and ubiquitin-protein transferase activity. And, the KEGG pathways mainly included the synaptic vesicle cycle, long-term potentiation, long-term depression, glutamatergic synapse, and calcium signaling pathways. Importantly, accumulative exposure (SL10 group) caused more differential expressed proteins than single exposure (S10 group or L10 group). In conclusion, 10 mW/cm2 S or L band microwave induced numerous differential expressed proteins in the hippocampus, while accumulative exposure evoked strongest responses. These proteins were closely associated with cognitive functions and were sensitive to microwave.

Light Affects Mood and Learning through Distinct Retina-Brain Pathways.

Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

BACKGROUND: Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. PROCEDURE: The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). RESULTS: Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. CONCLUSIONS: These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning.

Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain.

Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes.

Extremely Low Frequency Electromagnetic Fields impair the Cognitive and Motor Abilities of Honey Bees.

Extremely low frequency electromagnetic field (ELF EMF) pollution from overhead powerlines is known to cause biological effects across many phyla, but these effects are poorly understood. Honey bees are important pollinators across the globe and due to their foraging flights are exposed to relatively high levels of ELF EMF in proximity to powerlines. Here we ask how acute exposure to 50 Hz ELF EMFs at levels ranging from 20-100 µT, found at ground level below powerline conductors, to 1000-7000 µT, found within 1 m of the conductors, affects honey bee olfactory learning, flight, foraging activity and feeding. ELF EMF exposure was found to reduce learning, alter flight dynamics, reduce the success of foraging flights towards food sources, and feeding. The results suggest that 50 Hz ELF EMFs emitted from powerlines may represent a prominent environmental stressor for honey bees, with the potential to impact on their cognitive and motor abilities, which could in turn reduce their ability to pollinate crops.

From the Cover: 2.45-GHz Microwave Radiation Impairs Hippocampal Learning and Spatial Memory: Involvement of Local Stress Mechanism-Induced Suppression of iGluR/ERK/CREB Signaling.

Microwave (MW) radiation induced oxidative stress reduces dendritic arborization, spine density and number of hippocampal pyramidal neurons and hence, impair learning and spatial memory through p53-dependent/independent apoptosis of hippocampal neuronal and nonneuronal cells. However, the mechanisms responsible for MW radiation induced impairment in memory formation remains still unknown. This study elucidates the effect of short (15 days) and long-term (30 and 60 days) low level 2.45 GHz MW radiation-induced local stress on the hippocampal spatial memory formation pathway in adult male mice. Twelve-weeks old mice were exposed to 2.45 GHz MW radiation (continuous-wave with overall average Power density of 0.0248 mW/cm2 and overall average whole body SAR value of 0.0146 W/Kg) @ 2 h/d for 15, 30, and 60 days. Learning and spatial memory was assessed by 8-arm radial maze. We have investigated the alterations in serum corticosterone level and the expression of glucocorticoid receptor, corticotropin-releasing hormone (CRH), inducible nitric oxide synthase (i-NOS), iGluRs, PSD-95-neuronal NOS (n-NOS) system, protein kinase A, protein kinase Cε-ERK1/2-pERK1/2 in all the hippocampal subregions, viz. CA1, CA2, CA3, and DG through immunohistochemistry/immunofluorescence and alterations in the expression of hippocampal glucocorticoid receptor, CRH-receptor 1 (CRH-R1), cAMP-response element-binding (CREB), and phosphorylated-CREB (p-CREB) through western blot analysis. We observed that 2.45 GHz MW irradiated mice showed slow learning and significantly increased number of working and reference memory errors in radial maze task. Further, 2.45 GHz MW radiation exposure increases serum corticosterone level and the expression of CRH, CRH-R1, and i-NOS, while the expression of iGluRs, n-NOS, PSD-95, protein kinase Cε, protein kinase A, ERK-p-ERK, CREB, and p-CREB decreases in above mentioned hippocampal subregions in a duration dependent manner. Our findings led us to conclude that 2.45 GHz MW radiation exposure induced local stress suppresses signaling mechanism(s) of hippocampal memory formation.

No effects of transcranial DLPFC stimulation on implicit task sequence learning and consolidation.

Neurostimulation of the dorsolateral prefrontal cortex (DLPFC) can modulate performance in cognitive tasks. In a recent study, however, transcranial direct current stimulation (tDCS) of the DLPFC did not affect implicit task sequence learning and consolidation in a paradigm that involved bimanual responses. Because bimanual performance increases the coupling between homologous cortical areas of the hemispheres and left and right DLPFC were stimulated separately the null findings may have been due to the bimanual setup. The aim of the present study was to test the effect of neuro-stimulation on sequence learning in a uni-manual setup. For this purpose two experiments were conducted. In Experiment 1, the DLPFC was stimulated with tDCS. In Experiment 2 the DLPFC was stimulated with transcranial magnetic stimulation (TMS). In both experiments, consolidation was measured 24 hours later. The results showed that sequence learning was present in all conditions and sessions, but it was not influenced by stimulation. Likewise, consolidation of sequence learning was robust across sessions, but it was not influenced by stimulation. These results replicate and extend previous findings. They indicate that established tDCS and TMS protocols on the DLPFC do not influence implicit task sequence learning and consolidation.

Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles.

The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to "accelerated aging." One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as 56Fe, within 24-48h after exposure, and found that radiation primarily affects memory and not learning. Importantly, we observed that specific brain regions failed to upregulate antioxidant and anti-inflammatory mechanisms in response to this insult. To further examine these endogenous response mechanisms, we have supplemented young rats with diets rich in BB, which are known to contain high amounts of antioxidant-phytochemicals, prior to irradiation. Exposure to 56Fe caused significant neurochemical changes in hippocampus and frontal cortex, the two critical regions of the brain involved in cognitive function. BB supplementation significantly attenuated protein carbonylation, which was significantly increased by exposure to 56Fe in the hippocampus and frontal cortex. Moreover, BB supplementation significantly reduced radiation-induced elevations in NADPH-oxidoreductase-2 (NOX2) and cyclooxygenase-2 (COX-2), and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and frontal cortex. Overall results indicate that 56Fe particles may induce their toxic effects on hippocampus and frontal cortex by reactive oxygen species (ROS) overload, which can cause alterations in the neuronal environment, eventually leading to hippocampal neuronal death and subsequent impairment of cognitive function. Blueberry supplementation provides an effective preventative measure to reduce the ROS load on the CNS in an event of acute HZE exposure.

Transcranial infrared laser stimulation improves rule-based, but not information-integration, category learning in humans.

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation on category learning tasks. Transcranial infrared laser stimulation is a new non-invasive form of brain stimulation that shows promise for wide-ranging experimental and neuropsychological applications. It involves using infrared laser to enhance cerebral oxygenation and energy metabolism through upregulation of the respiratory enzyme cytochrome oxidase, the primary infrared photon acceptor in cells. Previous research found that transcranial infrared laser stimulation aimed at the prefrontal cortex can improve sustained attention, short-term memory, and executive function. In this study, we directly investigated the influence of transcranial infrared laser stimulation on two neurobiologically dissociable systems of category learning: a prefrontal cortex mediated reflective system that learns categories using explicit rules, and a striatally mediated reflexive learning system that forms gradual stimulus-response associations. Participants (n=118) received either active infrared laser to the lateral prefrontal cortex or sham (placebo) stimulation, and then learned one of two category structures-a rule-based structure optimally learned by the reflective system, or an information-integration structure optimally learned by the reflexive system. We found that prefrontal rule-based learning was substantially improved following transcranial infrared laser stimulation as compared to placebo (treatment X block interaction: F(1, 298)=5.117, p=0.024), while information-integration learning did not show significant group differences (treatment X block interaction: F(1, 288)=1.633, p=0.202). These results highlight the exciting potential of transcranial infrared laser stimulation for cognitive enhancement and provide insight into the neurobiological underpinnings of category learning.

tDCS over left M1 or DLPFC does not improve learning of a bimanual coordination task.

Previously, transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has resulted in improved performance in simple motor tasks. For a complex bimanual movement, studies using functional magnetic resonance imaging and transcranial magnetic stimulation indicated the involvement of the left dorsolateral prefrontal cortex (DLPFC) as well as left M1. Here we investigated the relative effect of up-regulating the cortical function in left DLPFC and left M1 with tDCS. Participants practised a complex bimanual task over four days while receiving either of five stimulation protocols: anodal tDCS applied over M1, anodal tDCS over DLPFC, sham tDCS over M1, sham tDCS over DLPFC, or no stimulation. Performance was measured at the start and end of each training day to make a distinction between acquisition and consolidation. Although task performance improved over days, no significant difference between stimulation protocols was observed, suggesting that anodal tDCS had little effect on learning the bimanual task regardless of the stimulation sites and learning phase (acquisition or consolidation). Interestingly, cognitive performance as well as corticomotor excitability did not change following stimulation. Accordingly, we found no evidence for behavioural or neurophysiological changes following tDCS over left M1 or left DLPFC in learning a complex bimanual task.

Exposure to low doses of 137cesium and nicotine during postnatal development modifies anxiety levels, learning, and spatial memory performance in mice.

Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation (137Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium (137Cs) (4000 and 8000 Bq/kg) and/or Nic (100 µg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137Cs.