Effects of electromagnetic fields on the organism can be divided into thermal effect and non-thermal effect. The thermal effect makes the function of heat transmission in tissues disordered, then causing tissue damage and cell death. Non-thermal effect changes the physiological and biochemical processes of the organism, but does not cause the increase of temperature. It is generally considered that high-frequency electromagnetic waves cause mainly the thermal effect, while low-frequency ones cause the non-thermal effect. The non-thermal effect has been one of the research focuses in recent years[11]. The PEMFs used in this study belong to fast changing electromagnetic fields. Their average energy is nearly zero. Their effect on body cells is mainly non-thermal effect and is concentrated on the cell membrane[12]. As for the effect of fast changing electronic pulse, the tissue cells can produce an enhanced transmembrane potential based on primary resting potential of cell membrane. Structural changes in the cell membrane occur and the membrane becomes more permeable to molecular transport[13] which results from the formation of membrane pores (electroporation)[14-15]. Under long-time exposure to low-intensity electromagnetic pulse, the pores continue to grow, causing the loss of membrane integrity and resulting in cell death[16], which then affects the capability of learning and memory. In the present study, we determined the expression of neural stem cell proliferation and nestin protein in the hippocampus of offspring rats. The nestin-positive cells in the hippocampus of control offspring rats were concentrated in small regions of CA1 and CA2, the dye was weak, and the cell body was small. Compared with the control group, nestin-positive cells were more, the expression areas in the CA1 and CA2 subregions were larger, the neuritis of the positive cells were more, and the dye was deeper in the PPEMFs group. In the PPEMFs group, the nestin protein expression was higher in female rat offspring than in male rat offspring, but there was no significant difference between female and male rat offspring in the control group. Nestin-positive cells are regarded as progenitor neural cells[17-18], so the results indicate that certain time and intensity of PEMFs to pregnant rats could increase the number of neural stem cells. It is known that certain intensity of PEMFs can cause the damage of the organism, tissues and cells, while the neural stem cells can proliferate responsively in pathological condition such as injury[19-21]. Many studies demonstrate that different kinds of brain injuries stimulate hippocampal neurogenesis[22-24]. Therefore, we think that PPEMFs may cause cell damage in the hippocampal CA1 and CA2 subregions of rat offspring, and the neural stem cells proliferate spontaneously in the injury area[25], and the neurites are netted to prevent the injury from expanding, which is beneficial for the reparation of the injury region. It is the compensable reaction of the body to brain injury. Researchers consider that the moving of nestin-positive cells to adjacent injury area after brain trauma may be not the representation of neural stem cells differentiation into neurons, but the reaction of astrocytes to the trauma[26-27]. Because the expression of nestin-positive cell reactive proliferation is very similar to that of astrocytes to injury area after brain trauma, so the existence of most nestin-positive cells in CA1 and CA2 subregions may be the reaction of astrocytes to brain injury. The notion that astrocytes serve as potential sources for neurogenesis remains speculative[28-29]. In addition, another aspect is the migrating of the DG cells.
Brdu-positive cells are regarded as the cells possessed activation of proliferation[30]. In the present study, we found that Brdu-positive cells were mainly distributed in the DG. The Brdu-positive cells in the DG region of PEMFs offspring significantly increased in number compared with those in the control group. The Brdu-positive cells of female offspring outnumbered those of male offspring in the PPEMFs group, but there was no significant difference between female and male offspring in the control group. It is known that the hippocampal DG is one of the regions where the neural stem cells are produced[31]. Previous studies have shown that brain injury induces neurogenesis primarily in the DG[32-34]. There are “still” and “dormant” stem cell groups in the DG region which do not express any distinctive antigen[35]. But stress and aging can cause the neurogenesis in the DG of the hippocampus[36-37]. Under the PPEMFs stress, the latent energy of splitting is activated and then the capability of proliferation increases. The migration of regenerating cells to CA1 and CA2 injury regions produces the compensable action.
In addition, the neural stem cell proliferation and nestin protein expression in PEMFs female offspring increased more significantly than those in male rat offspring. This may be because the activity of placenta 11β-HSD in female fetus is low[38]. Therefore, the damage is more serious, and neural stem cell proliferation in the injured region is greater in female rat offspring than in male rat offspring.
It is not very clear why the brain injury caused by PEMFs could induce the increase of cells produced in the hippocampal DG region and the nestin protein expression in injury region. This may be related to the change of permeability of cell membrane and the change of the ion concentration caused by PEMFs stress[13, 39]. Studies demonstrated that electromagnetic stimulation can cause the increase of cellular calcium ion density[40-41], induce the expression of certain specific genes, lead to the phosphorylation of protein, the change of cellular enzyme activity and the activation of signal transduction which modulates cell proliferation and apoptosis[42-44]. But it needs to be further investigated how these cascade reactions can affect stem cell proliferation, whether these cells can be differentiated into neural cells and whether these cascade reactions can affect the recognition and behavioral function.
