Extremely low frequency electromagnetic field exposure causes cognitive impairment associated with alteration of the glutamate level, MAPK pathway activation and decreased CREB phosphorylation in mice hippocampus: reversal by procyanidins extracted from the lotus seedpod.

Abstract

Lotus seedpod procyanidins (LSPCs) could effectively prevent learning and memory damage and oxidative damage caused by extremely low frequency electromagnetic field (ELF-EMF) exposure. However, LSPCs protect neurons from ELF-EMF-induced damage by mechanisms currently not clear. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study we determined whether the ELF-EMF (50 Hz, 8 mT, 28 days) exposure induced alterations of glutamate release in mice hippocampus and explored the possible mechanism, and if LSPC treatment normalized its alterations. The results showed that ELF-EMF exposure induced the increased contents of glutamate, GABA, excessively activated NMDA receptors, increasing the number of NMDA receptor 2B (NR2B) and intracellular Ca(2+) concentration [Ca(2+)]i in hippocampus. In addition, ELF-EMF exposure decreased the ERK1/2 and CREB phosphorylation, which suggested that the Ca(2+) influx induced by the ELF-EMF exposure stimulated activity of the ERK, in turn, influences the expression of downstream proteins in this signaling pathway. Besides, ELF-EMF exposure also increased JNK1/2 phosphorylation through the activated ASK1, which plays a pivotal role in hippocampal neuronal cell death. However, oral administration of LSPCs (especially 60 and 90 mg kg(-1)) markedly improved expressions of p-CREB, p-ERK1/2 and p-JNK1/2, accompanied by decreased levels of glutamate, GABA, [Ca(2+)]i and NR2B. Thus, the results from the present study suggest that p-ERK1/2, p-JNK1/2, [Ca(2+)]i and p-CREB expression normalized, possibly via a NMDA receptor-channel through the changes of GABA, glutamate and NR2B, which might be responsible for the neuroprotective or memory enhancing effects of LSPCs.

AI evidence extraction

Main findings

In mice, ELF-EMF exposure (50 Hz, 8 mT, 28 days) was associated with increased hippocampal glutamate and GABA contents, excessive NMDA receptor activation with increased NR2B and intracellular Ca2+, and altered MAPK-related signaling (decreased ERK1/2 and CREB phosphorylation; increased JNK1/2 phosphorylation via activated ASK1). Oral lotus seedpod procyanidins (notably 60 and 90 mg/kg) were reported to reverse/normalize several of these biochemical changes and were described as preventing learning/memory and oxidative damage from ELF-EMF exposure.

Outcomes measured

• Learning and memory damage/cognitive impairment
• Oxidative damage
• Hippocampal glutamate content
• Hippocampal GABA content
• NMDA receptor activation
• NR2B (NMDA receptor 2B) levels/number
• Intracellular Ca2+ concentration ([Ca2+]i)
• ERK1/2 phosphorylation
• CREB phosphorylation
• JNK1/2 phosphorylation
• ASK1 activation
• Hippocampal neuronal cell death (implied via pathway)

Limitations

• Sample size not reported in abstract
• Behavioral/cognitive testing methods and quantitative results not described in abstract
• Exposure source/setup not specified beyond frequency, flux density, and duration
• Mechanistic interpretations are suggested but causal pathway details are not fully established in abstract

Suggested hubs

• animal-studies (0.9)
  Mouse study assessing neurobehavioral/biochemical effects of ELF-EMF exposure and an intervention.
• elf-emf (0.85)
  Exposure is extremely low frequency EMF (50 Hz) at 8 mT for 28 days.

{
    "study_type": "animal",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 5.00000000000000023960868011929647991564706899225711822509765625e-5,
        "sar_wkg": null,
        "duration": "28 days"
    },
    "population": "Mice (hippocampus)",
    "sample_size": null,
    "outcomes": [
        "Learning and memory damage/cognitive impairment",
        "Oxidative damage",
        "Hippocampal glutamate content",
        "Hippocampal GABA content",
        "NMDA receptor activation",
        "NR2B (NMDA receptor 2B) levels/number",
        "Intracellular Ca2+ concentration ([Ca2+]i)",
        "ERK1/2 phosphorylation",
        "CREB phosphorylation",
        "JNK1/2 phosphorylation",
        "ASK1 activation",
        "Hippocampal neuronal cell death (implied via pathway)"
    ],
    "main_findings": "In mice, ELF-EMF exposure (50 Hz, 8 mT, 28 days) was associated with increased hippocampal glutamate and GABA contents, excessive NMDA receptor activation with increased NR2B and intracellular Ca2+, and altered MAPK-related signaling (decreased ERK1/2 and CREB phosphorylation; increased JNK1/2 phosphorylation via activated ASK1). Oral lotus seedpod procyanidins (notably 60 and 90 mg/kg) were reported to reverse/normalize several of these biochemical changes and were described as preventing learning/memory and oxidative damage from ELF-EMF exposure.",
    "effect_direction": "harm",
    "limitations": [
        "Sample size not reported in abstract",
        "Behavioral/cognitive testing methods and quantitative results not described in abstract",
        "Exposure source/setup not specified beyond frequency, flux density, and duration",
        "Mechanistic interpretations are suggested but causal pathway details are not fully established in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "extremely low frequency",
        "ELF-EMF",
        "50 Hz",
        "8 mT",
        "mice",
        "hippocampus",
        "cognitive impairment",
        "learning and memory",
        "glutamate",
        "GABA",
        "NMDA receptor",
        "NR2B",
        "calcium",
        "MAPK",
        "ERK1/2",
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        "CREB",
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        "procyanidins",
        "lotus seedpod"
    ],
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            "reason": "Exposure is extremely low frequency EMF (50 Hz) at 8 mT for 28 days."
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}

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