Synaptic Plasticity in the Hippocampus: Effects of Estrogen from the Gonads or Hippocampus?

Different effects of estrogen on synaptic plasticity have [corrected] been reported. Here, we summarise effects of low, gonad-derived serum estrogen concentrations, of intermediate concentrations, provided by hippocampal cells, and of pharmacological doses of estrogen on synapses and spines and on the expression of synaptic proteins. No effects of low concentrations were found. To study the effects of hippocampus-derived estradiol, we inhibited hippocampal estrogen synthesis by treatment of hippocampal cell cultures with letrozole, an aromatase inhibitor. Alternatively, we used siRNA against Steroidogenic acute regulatory protein (StAR). Spines, synapses, and synaptic proteins were significantly down regulated in response to letrozole and in siRNA-StAR transfected cells. Application of high pharmacological doses of estradiol promoted only synaptophysin expression, a presynaptic protein, but did not increase the number of boutons. Our results point to an essential role of endogenous hippocampal estrogen in hippocampal synaptic plasticity rather than to a direct influence of estrogens derived from peripheral sources, such as the gonads.     

Effects of Chronic Stress and Phenytoin on the Long-term Potentiation （LTP） in Rat Hippocampal CA1 Region

Stress is the response to stimulation from inside andoutside with complicated effects on organisms. Appropri-ate stressful reactions are helpful in resisting diseases byactivating unspecific modulation system, while severe orprolonged stresses are harmful and even induce mentaland physical disorders such as recurrent depression, post-traumatic stress disorder (PTSD), Alzheimer’s disease andepilepsy [1]. Hippocampus, a main brain region of keyimportance for learning, memory and emotion, is t…     

An Investigation Into the Effects of Long-Term 50-Hz Power-Frequency Electromagnetic Field Exposure on Hematogram,Blood Chemistry,Fibrosis, and Oxidant Stress Status in the Liver and the Kidney From Sprague–Dawley Rats

Power-frequency electromagnetic fields (PF-EMFs) at 50 Hz are potential health risk factors. This study aimed to explore the effects of long-term exposure to 50-Hz PF-EMFs on general physiological conditions in Sprague–Dawley (SD) rats. During a 24-week exposure period, the body mass and water and food intake of the animals were recorded regularly. The hematologic parameters were detected every 12 weeks, and blood chemistry analyses were performed every 4 weeks. After sacrifice, morphology was identified by hematoxylin–eosin, Masson, and immunohistochemical staining. Fibrosis-related gene expression and oxidative stress status were also detected. Compared with the control group, exposure to 30, 100, or 500 μT PF-EMF did not exert any effect on body mass, food intake, or water intake. Similarly, no significant differences were found in hematologic parameters or blood chemistry analyses among these groups. Furthermore, morphological assays showed that exposure to PF-EMFs had no influence on the structure of the liver or kidney. Finally, fibrosis-related gene expression and oxidative stress status were unaltered by PF-EMF exposure. The present study indicates that 24 weeks of exposure to PF-EMFs at intensities of 30, 100, or 500 μT might not affect hemograms, blood chemistry, fibrosis, or oxidative stress in the liver or kidney in SD rats. © 2020 Bioelectromagnetics Society     

Effect of Long-Term Exposure to a Randomly Varied 50 Hz Power Frequency Magnetic Field on the Fertility of the Mouse

A double blind study on BALB/c mice was conducted to examine the effects of extremely low-frequency electromagnetic fields on fertility. The mice were continuously exposed or sham-exposed from conception for two generations to magnetic fields varying between 0.5 and 77?μT. Biological parameters related to fertility were evaluated. Serum testosterone levels and mass of testes and adrenals were determined. No significant difference was found between the sham-exposed and exposed groups for all the biological endpoints, except for sperm motility. A significant difference between the two groups was found prior to the swim-up test with quantitative analysis of sperm motility as well as after the swim-up test for quantitative and qualitative analysis of sperm motility. ELF-EMFs significantly decreased the number of living sperm and the quality of movement of sperm, although these adversities did not impact on the outcome of the other parameters investigated.     

Effect of Prenatal Stress on the Pituitary–Adrenal Axis in Blue Foxes

Handling is a source of stress for farm bred blue foxes. The influence of handling during the late gestation period on the pituitary–adrenal axis was studied in 10-day old male and female blue foxes. Cortisol and progesterone were measured by radioimmunoassay in the plasma, adrenal homogenates, and in vitro incubates from animals of both sexes. Adrenals were incubated in vitro in the absence or presence of ACTH. In addition, the adrenal weight and plasma concentration of ACTH were assessed. In cubs of both sexes, the adrenal weight was decreased after prenatal stress treatment. The plasma concentration of progesterone and the adrenal cortisol in vitro production were elevated in the prenatally stressed female cubs, as compared to the control, along with the adrenal progesterone in vitro production in prenatally stressed male cubs. The adrenal cortisol and progesterone content and plasma ACTH and cortisol concentrations were not affected by prenatal stress. In conclusion, the results of this study suggest that the prenatal stress induced by handling pregnant vixens can affect the pituitary–adrenal axis in neonatal offspring, this effect being more pronounced in female cubs.     

Effect of the “zero” Magnetic Field on Early Embryogenesis in Mice

It was shown that the 250-fold screening of the geomagnetic field (GMF) (“zero” magnetic field with an induction of 0.2?μT) affects early embryogenesis and the reproduction capacity of mice in vivo. Pregnant NMRI mice at the zygote stage placed in this “zero” magnetic field (MF) lost the ability to bear offspring babies although their embryos developed up to the blastocyst stage without any visible deviations from the norm. The abortion of development in the “zero” MF occurred after the exit of the blastocysts from the zona pellicida and invasion into the uterus during implantation. Histological analysis indicates that possible reasons of the abnormalities of postimplantation development are a decrease in the proliferative activity of embryonic cells and the impairment of the interaction between the trophoblast and endometrium, which finally results in the resorption of embryos in the uterus.     

Effects of ω-Amino Acids and Related Compounds on Staphylococcal Infections in Mice: a Combined Prophylactic-Therapeutic Procedure

By a short-term combined prophylactic-therapeutic procedure, the following compounds were found to be active against staphylococcal infections in Swiss mice: gamma-aminobutyric acid, gamma-amino-beta-hydroxybutyric acid (GABOB), delta-amino-valeric acid (DAVA), epsilon-aminocaproic acid (EACA), trans-4-aminomethylcyclohexanecarboxylic acid (trans-AMCHA), taurine, and cysteic acid. Many of these compounds had displayed limited or no activity by a previously used prophylactic procedure. Although DAVA and GABOB were the most potent of the straight-chain omega-amino acids, trans-AMCHA displayed the greatest antistaphylococcic activity of the omega-amino acids thus far investigated. Homocarnosine (gamma-aminobutyrl histidine, which also was active by the prophylactic procedure) equalled trans-AMCHA in activity. Taurine was similar in potency to DAVA, and the activity of cysteic acid approximated that of EACA.     

Epigenetic DNA Methylation in Radiation Biology: On the Field or on the Sidelines?

DNA methylation has been studied with regard to chemotherapeutics for a number of years. The radiation field has just begun to look at this in the context of radiotherapy or radiation exposure. So far, the data suggest that radiation induces epigenetic reprogramming which indicates a purposeful response that influences the cell fate or alters the response to future exposure. Further studies may result in discovery of biomarkers for radiotherapy outcome or prediction of the degree of radiation resistance. Past and ongoing development of DNMT1 inhibitors that lead to DNA hypomethylation appear to sensitize many tumor types to radiation and may be an area with long term clinical implications. J. Cell. Biochem. 116: 212–217, 2015. © 2014 Wiley Periodicals, Inc.     

Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice

Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer’s disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3?×?TgAD mice were treated with fluoxetine for 15 days, and then the influence of fluoxetine was detected at 20 days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3?×?TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.     

Hippocampal synaptic plasticity: role in spatial learning or the automatic recording of attended experience?

Allocentric spatial learning can sometimes occur in one trial. The incorporation of information into a spatial representation may, therefore, obey a one-trial correlational learning rule rather than a multi-trial error-correcting rule. It has been suggested that physiological implementation of such a rule could be mediated by N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) in the hippocampus, as its induction obeys a correlational type of synaptic learning rule. Support for this idea came originally from the finding that intracerebral infusion of the NMDA antagonist AP5 impairs spatial learning, but studies summarized in the first part of this paper have called it into question. First, rats previously given experience of spatial learning in a watermaze can learn a new spatial reference memory task at a normal rate despite an appreciable NMDA receptor blockade. Second, the classical phenomenon of ''blocking'' occurs in spatial learning. The latter finding implies that spatial learning can also be sensitive to an animal''s expectations about reward and so depend on more than the detection of simple spatial correlations. In this paper a new hypothesis is proposed about the function of hippocampal LTP. This hypothesis retains the idea that LTP subserves rapid one-trial memory, but abandons the notion that it serves any specific role in the geometric aspects of spatial learning. It is suggested that LTP participates in the automatic recording of attended experience'': a subsystem of episodic memory in which events are temporarily remembered in association with the contexts in which they occur. An automatic correlational form of synaptic plasticity is ideally suited to the online registration of context event associations. In support, it is reported that the ability of rats to remember the most recent place they have visited in a familiar environment is exquisitely sensitive to AP5 in a delay-dependent manner. Moreover, new studies of the lasting persistence of NMDA-dependent LTP, known to require protein synthesis, point to intracellular mechanisms that enable transient synaptic changes to be stabilized if they occur in close temporal proximity to important events. This new property of hippocampal LTP is a desirable characteristic of an event memory system.     

Effects of Chronic Restraint Stress and 17-β-Estradiol Replacement on Oxidative Stress in the Spinal Cord of Ovariectomized Female Rats

Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX) female rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided into controls and chronically stressed (for 40 days). Our findings demonstrate that chronic stress decreased TRAP, and increased SOD activity in spinal cord homogenates from ovariectomized female rats and had no effect on GPx activity. On the other hand, groups receiving 17β-estradiol replacement presented a decreased GPx activity, but no alteration in TRAP and in SOD activity. No differences in the TBARS test were found in any of the groups analyzed. In conclusion, our results support the idea that chronic stress induces an imbalance between SOD and GPx activities, additionally decreasing TRAP. Estradiol replacement did not reverse the effects of chronic stress, but induced a decrease in GPx activity. Therefore, estradiol replacement in ovariectomized chronically stressed rats could make the spinal cord more susceptible to oxidative injury.     

Protective Effect of ACE Inhibitors on Ischemia-Reperfusion-induced Arrhythmias in Rats: Is this Effect Related to the Free Radical Scavenging Action of these Drugs?

The antiarrhythmic effects of captopril, a sulphydrylcontaining angiotensin converting enzyme (ACE) inhibitor, were compared with those of the non-sulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg^-1) and lisinopril (0.1, 0.3 or 1 mg kg^-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg^-) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg^-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.     

Strict or Graduated Punishment? Effect of Punishment Strictness on the Evolution of Cooperation in Continuous Public Goods Games

Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher’s threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player’s death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results.     

The Effect of a “Zero” Magnetic Field on the Production of Reactive Oxygen Species in Neutrophils

Exposure of mouse peritoneal neutrophils to hypomagnetic conditions (magnetic shielding, a residual static magnetic field of 20 nT) for 1.5 h decreased the level of intracellular reactive oxygen species as recorded by changes in the fluorescence intensity of 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123 oxidation products. The effect of a hypomagnetic field was similarly observed after adding a respiratory burst activator (the formylated peptide N-formyl–Met–Leu–Phe or phorbol 12-meristate-13-acetate) to a low concentration.     

Will Temperature Effects or Phenotypic Plasticity Determine the Thermal Response of a Heterothermic Tropical Bat to Climate Change?

The proportion of organisms exposed to warm conditions is predicted to increase during global warming. To better understand how bats might respond to climate change, we aimed to obtain the first data on how use of torpor, a crucial survival strategy of small bats, is affected by temperature in the tropics. Over two mild winters, tropical free-ranging bats (Nyctophilus bifax, 10 g, n = 13) used torpor on 95% of study days and were torpid for 33.5±18.8% of 113 days measured. Torpor duration was temperature-dependent and an increase in ambient temperature by the predicted 2°C for the 21^st century would decrease the time in torpor to 21.8%. However, comparisons among Nyctophilus populations show that regional phenotypic plasticity attenuates temperature effects on torpor patterns. Our data suggest that heterothermy is important for energy budgeting of bats even under warm conditions and that flexible torpor use will enhance bats’ chance of survival during climate change.     

Developmental Exposure to Polychlorinated Biphenyls or Dioxin: Do Changes in Thyroid Function Mediate Effects on Spatial Learning?

Polychlorinated biphenyls (PCBs) and dioxins are widespreadenvironmental contaminants that are suspected of causing cognitivedeficits in children exposed in utero. Very little is knownabout which of the PCB and dioxin congeners present in the environmentare responsible for the changes in cognitive function or aboutthe mechanisms through which these chemicals affect the centralnervous system (CNS). Because both PCBs and dioxins reduce circulatingthyroid hormone levels, it has been proposed that these chemicalsmay affect CNS function indirectly by reducing the availabilityof thyroid hormone to the brain during development. Thyroidhormones play a critical role in brain development, and spatiallearning and memory is one of the behavioral functions mostseverely affected by neonatal hypothyroidism. In the studiesreviewed here, we investigated the effects of three ortho-substitutedPCBs, two coplanar PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) on spatial learning and memory in the rat. Pups exposedto PCBs or TCDD in utero and during lactation were tested whenthey reached adulthood. All three ortho-substituted PCBs causeddeficits in spatial learning, but only two of the three reducedcirculating thyroid hormone concentrations. Furthermore, thelearning deficit was observed only in females, but thyroid hormoneswere equally depressed in males and females. Thus, the PCB-induceddeficit in spatial learning did not appear to be mediated bythe decreased thyroid hormone levels. TCDD and coplanar PCBscaused moderate reductions in thyroid hormone, but facilitatedrather than impaired spatial learning, an effect that has beenreported in neonatally hyperthyroid rats. The possibility thatTCDD and coplanar PCBs may act as "mixed" thyroid agonists/antagonistscausing hypothyroid-like effects in some tissues and hyperthyroid-likeeffects in other tissues is discussed.     

Effects of the trematode Maritrema novaezealandensis on the behaviour of its amphipod host: adaptive or not?

There are many recorded cases of parasites that are capable of altering the behaviour of their host to enhance their transmission efficiency. However, not all of these cases are necessarily the results of the parasites actively manipulating host behaviour; they may rather be the 'by-products' of pathology caused by the parasite's presence. This study investigates the effect of the microphallid trematode Maritrema novaezealandensis on the behaviour of one of its crustacean intermediate hosts, the amphipod Paracalliope novizealandiae. Uninfected amphipods were experimentally infected by exposure to M. novaezealandensis cercariae. The activity level and vertical position of experimentally infected amphipods were compared with uninfected amphipods at 2 weeks and 6 weeks post-infection, i.e. both before and after the parasite achieved infectivity to its definitive host. Infected amphipods were found to exhibit significantly lower levels of activity and to occur significantly lower in the water column than uninfected controls during both periods. Based on the timing of the change in behaviour exhibited by infected amphipods, the results suggest that the altered behaviour exhibited by P. novizealandiae infected with M. novaezealandensis is most likely due to pathology caused by the parasite rather than a case of active, and adaptive, behavioural manipulation.     

Gender and Age Differences in the Suppressive Effect of a 50 Hz Electric Field on the Immobilization-Induced Increase of Plasma Glucocorticoid in Mice

We developed an experimental system to characterize the suppressive effect of extremely low-frequency (ELF) electric fields (EFs) on the stress response. We assessed differences in the EF effects by age and gender. Control, EF-alone, immobilization-alone, and co-treated groups were subjected to an EF (50 Hz, 10 kV/m). Co-treated mice were exposed to the EF for 60 min, with immobilization during the latter half. Our results indicate that the suppressive effects of ELF EFs on the stress response in immobilized mice occur regardless of gender or age. As stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in animal, and perhaps human, health. Bioelectromagnetics. 2020;41:156–163. © 2019 Bioelectromagnetics Society.