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. 2023 Apr;13(4):e2949.
doi: 10.1002/brb3.2949. Epub 2023 Mar 21.

Effect of prenatal stress and extremely low-frequency electromagnetic fields on anxiety-like behavior in female rats: With an emphasis on prefrontal cortex and hippocampus

Ehsan Hosseini  1 , Davoud Kianifard  2
Affiliations

Effect of prenatal stress and extremely low-frequency electromagnetic fields on anxiety-like behavior in female rats: With an emphasis on prefrontal cortex and hippocampus

Ehsan Hosseini et al. Brain Behav. 2023 Apr.

Abstract

Objective: Prenatal stress (PS) is a problematic situation resulting in psychological implications such as social anxiety. Ubiquitous extremely low-frequency electromagnetic fields (ELF-EMF) have been confirmed as a potential physiological stressor; however, useful neuroregenerative effect of these types of electromagnetic fields has also frequently been reported. The aim of the present study was to survey the interaction of PS and ELF-EMF on anxiety-like behavior.

Method: A total of 24 female rats 40 days of age were distributed into four groups of 6 rats each: control, stress (their mothers were exposed to stress), EMF (their mothers underwent to ELF-EMF), and EMF/stress (their mothers concurrently underwent to stress and ELF-EMF). The rats were assayed using elevated plus-maze and open field tests.

Results: Expressions of the hippocampus GAP-43, BDNF, and caspase-3 (cas-3) were detected by immunohistochemistry in Cornu Ammonis 1 (CA1) and dentate gyrus (DG) of the hippocampus and prefrontal cortex (PFC). Anxiety-like behavior increased in all treatment groups. Rats in the EMF/stress group presented more serious anxiety-like behavior. In all treatment groups, upregulated expression of cas-3 was seen in PFC, DG, and CA1 and downregulated expression of BDNF and GAP-43 was seen in PFC and DG and the CA1. Histomorphological study showed vast neurodegenerative changes in the hippocampus and PFC.

Conclusion: The results showed ,female rats that underwent PS or/and EMF exhibited critical anxiety-like behavior and this process may be attributed to neurodegeneration in PFC and DG of the hippocampus and possibly decreased synaptic plasticity so-called areas.

Keywords: BDNF; GAP-43; anxiety-like behavior; cas-3; electromagnetic fields; female rat; hippocampus; prefrontal cortex; prenatal stress.

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Conflict of interest statement

The authors declare that they have not any conflict of interest.

Figures

FLOW CHART 1
FLOW CHART 1
Timeline of the research, EPM: Elevated plus maze, OFT: Open field test.
FIGURE 1
FIGURE 1
Helmholtz‐coil apparatus for the EMF exposure.
FIGURE 2
FIGURE 2
Effect of EMF on center square entries (a), leaning (b), rearing (c), grooming (d), defecation (e), after prenatal stress. Data are shown as mean ± SEM (n = 6 per group). Two‐way ANOVA, followed by Tukey's post hoc test: *p < .05, **p < .01, ***p < .001. ANOVA, analysis of variance; Ctrl, control; EMF, electromagnetic field; S, prenatal stress.
FIGURE 3
FIGURE 3
Immunohistochemistry analysis in the PFC. (a) Representative photomicrograph of immunohistochemistry. (b) Cas3‐positive area in PFC; (c) BDNF‐positive area in PFC; (d) GAP43‐positive area in PFC. All scale bars were 50 μm. The values represent the mean ± SEM,**p < 0.01, ***p < 0.001. Ctrl, control, EMF, extremely low‐frequency electromagnetic field, S, prenatal stress; EMF‐S: combined extremely low‐frequency electromagnetic field with prenatal stress; PFC, prefrontal cortex.
FIGURE 4
FIGURE 4
Immunohistochemistry analysis in the CA1 of hippocampus. (a) Representative photomicrograph of immunohistochemistry. (b) Cas3‐positive area, (c) BDNF‐positive area, (d) GAP43‐positive area. All scale bars were 50 μm. The values represent the mean ± SEM, **p < 0.01, ***p < 0.001. Ctrl, control; EMF, extremely low‐frequency electromagnetic field; S, prenatal stress; EMF‐S, combined extremely low‐frequency electromagnetic field with prenatal stress; PFC, prefrontal cortex; CA 1, Cornu Ammonis 1.
FIGURE 5
FIGURE 5
Immunohistochemistry analysis in the dentate gyrus of Hippocampus. (a) Representative photomicrograph of immunohistochemistry. (b) Cas3‐positive area in dentate gyrus, (c) BDNF‐positive area in dentate gyrus, (d) GAP43‐positive area in dentate gyrus. All scale bars were 50 μm. The values represent the mean ± SEM,*p < .05, **p < .01, ***p < .001. Ctrl, control; EMF, extremely low‐frequency electromagnetic field; S, prenatal stress; EMF‐S, combined extremely low‐frequency electromagnetic field with prenatal stress; DG, dentate gyrus.
FIGURE 6
FIGURE 6
The effect of PS an ELF‐EMF on histomorphomtry of prefrontal cortex. Data are shown as mean ± SEM (n = 6 per group). Two‐way ANOVA, followed by Tukey's post hoc test: *p < .05, **p < .01, ***p < .001. ANOVA, analysis of variance; STR, stress; MG, extremly low‐frequency electromagnetic field.
FIGURE 7
FIGURE 7
The effect of PS an ELF‐EMF on histomorphomtry of hippocampus. Data are shown as mean ± SEM (n = 6 per group). Two‐way ANOVA, followed by Tukey's post hoc test: *p < .05, **p < .01 ***p < 0.001. ANOVA, analysis of variance; STR, stress; MG, extremly low‐frequency electromagnetic field.
FIGURE 8
FIGURE 8
Coronal section of prefrontal cortex. (a) Control group. Regular cellular arrangement has been seen in different layers. Neurons with normal structure (inside square) with astrocytes (arrows) are observable. Pia matter (PM), molecular layer (ML), external pyramidal layer (EPL), internal pyramidal layer (IPL), CRT (cortical region), white matter (WM); blood capillary (BC). (b) Stress group. Structural alteration with nuclear condensation in pyramidal neurons is visible (inside square). Astrocytes (arrows). (c) ELF‐EMF group. Structural alterations are seen in neurons (inside squares). Increase of perivascular space (arrows) is visible. (d) ELF‐EMF/Stress group. Structural alterations are seen in neurons (inside square). H&E staining. Magnification 200×.
FIGURE 9
FIGURE 9
The structure of dentate gyrus in sagittal section of hippocampus. (a) Normal structure of neurons is visible in various parts. Hilus (H), molecular layer (M), granular layer (G), cornu ammonis (CA). (b, c, d) Stress, ELF‐EMF, and ELF‐EMF/stress groups respectively. (e) Higher magnification of dentate gyrus of control group with normal structure of various cellular layers. (f) Higher magnification of dentate gyrus of stress group. Structural alterations of neurons of granular layer is observable (inside square). Hilus (H), molecular layer (ML), granular layer (GL), the CA4 subfield of cornu ammonis (CA). (g) Higher magnification of dentate gyrus of ELF‐EMF field group. Alterations of neurons are observable (inside square). Vascular hyperemia (arrow) is visible. (h) Higher magnification of dentate gyrus of ELF‐EMF/Stress group. Structural alterations of neurons from CA4 are observable (inside squares). Nuclear condensation of granular neurons (arrow) is visible. H&E staining. Magnification a–d 40×, e–h 200×.
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