Open Access

Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway

  • Authors:
    • Ling-Ling Xie
    • Shan-Shan Li
    • Yong-Jian Fan
    • Man-Man Qi
    • Zhuang-Zhuang Li
  • View Affiliations

  • Published online on: January 31, 2022     https://doi.org/10.3892/etm.2022.11173
  • Article Number: 248
  • Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melatonin is a hormone produced by the pineal gland. Given its capabilities of neuroprotection and low neurotoxicity, melatonin could be a therapeutic strategy for traumatic brain injury (TBI). The present study was conducted to determine the neuroprotective effects of melatonin on TBI‑induced anxiety and the possible molecular mechanism. Rats were randomly divided into seven groups. The rodent model of TBI was established using the weight‑drop method. Melatonin was administered by intraperitoneal injection at a dose of 10 mg/kg after TBI. H89 (0.02 mg/kg), a special protein kinase A (PKA) inhibitor, or dibutyryl‑cyclic adenosine monophosphate (cAMP; 0.1 mg/kg), an activator of PKA, were administered by stereotactic injection of the brain to evaluate the roles of PKA and cAMP‑response element‑binding protein (CREB) in melatonin‑related mood regulation, respectively. At 30 days post‑TBI, the changes in anxiety‑like behaviors in rats were measured using the open field and elevated plus maze tests. At 24 h post‑TBI, the number of activated astrocytes and neuronal apoptosis were evaluated using immunofluorescence assay. The expression levels of inflammatory cytokines (TNF‑α and IL‑6) in the amygdala were measured using an enzyme‑linked immunosorbent assay. The expression levels of PKA, phosphorylated (p)‑PKA, CREB, p‑CREB, NF‑κB and p‑NF‑κB in the amygdala were detected using western blotting. It was revealed that melatonin partially reversed TBI‑induced anxiety‑like behavior in rats, and decreased the number of activated astrocytes and neuronal apoptosis in the amygdala induced by TBI. H89 partially blocked the neuroprotective effects of melatonin; while dibutyryl‑cAMP not only reduced the H89‑induced emotional disturbance but also enhanced the protective effects of melatonin against TBI. Overall, melatonin can alleviate TBI‑induced anxiety‑like behaviors in rats. Moreover, the underlying mechanism may be associated with the activation of the PKA/CREB signaling pathway.
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April-2022
Volume 23 Issue 4

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Spandidos Publications style
Xie L, Li S, Fan Y, Qi M and Li Z: Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway. Exp Ther Med 23: 248, 2022.
APA
Xie, L., Li, S., Fan, Y., Qi, M., & Li, Z. (2022). Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway. Experimental and Therapeutic Medicine, 23, 248. https://doi.org/10.3892/etm.2022.11173
MLA
Xie, L., Li, S., Fan, Y., Qi, M., Li, Z."Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway". Experimental and Therapeutic Medicine 23.4 (2022): 248.
Chicago
Xie, L., Li, S., Fan, Y., Qi, M., Li, Z."Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway". Experimental and Therapeutic Medicine 23, no. 4 (2022): 248. https://doi.org/10.3892/etm.2022.11173