Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells

  • Authors:
    • Tandra R. Chakraborty
    • Joshua Cohen
    • Darien Yohanan
    • Eilliut Alicea
    • Benjamin S. Weeks
    • Sanjoy Chakraborty
  • View Affiliations

  • Published online on: November 18, 2016     https://doi.org/10.3892/mmr.2016.5952
  • Pages: 5677-5684
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Abstract

Estrogen (E2) has been demonstrated to possess protective effects from hypoglycemic toxicity, particularly in the pancreas. In the central nervous system, several brain regions, such as the hypothalamus, are highly vulnerable to hypoglycemic injuries that may lead to seizures, coma, and mortality. The present study performed a novel in vitro assay of hypoglycemic injury to hypothalamic cells, and is the first study, to the best of our knowledge, to demonstrate that E2 protects hypothalamic cells from hypoglycemic toxicity. The toxic effects of hypoglycemia on hypothalamic cells in vitro was determined by performing cell counts, together with MTT and lactate dehydrogenase assays, using the N38 murine hypothalamic cell line. Following 24 and 48 h in hypoglycemic conditions, a 60 and 75% reduction in cell number and mitochondrial function was observed, which reached 80 and ~100% by 72 and 96 h, respectively. E2 treatment prevented the hypoglycemia‑induced loss in cell number and mitochondrial toxicity at 24 and 48 h. However at 72 and 96 h of hypoglycemic conditions, the neuroprotective effects of E2 on cell number or mitochondrial function was not significant or not present at all. In order to determine whether E2 exerted its effects through the AKT signaling pathway, the expression of proline‑rich AKT substrate of 40 kDa (PRAS40) was analyzed. No alterations in PRAS40 expression were observed when N38 cells were exposed to hypoglycemic shock. From the biochemical and molecular data obtained, the authors speculated that E2 exhibits neuroprotective effects against hypoglycemic shock in hypothalamic cells, which dissipates with time. Despite demonstrating no significant effect on total AKT/PRS40 activity, it is possible that E2 may mediate these neuroprotective effects by upregulating the phosphorylated‑AKT/pPRAS40 signaling pathway. The present study presented, to the best of our knowledge, the first in vitro model for hypoglycemic toxicity to hypothalamic cells, and provided evidence to suggest that E2 may protect hypothalamic cells from the damaging effects of hypoglycemia.
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December-2016
Volume 14 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chakraborty TR, Cohen J, Yohanan D, Alicea E, Weeks BS and Chakraborty S: Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells. Mol Med Rep 14: 5677-5684, 2016.
APA
Chakraborty, T.R., Cohen, J., Yohanan, D., Alicea, E., Weeks, B.S., & Chakraborty, S. (2016). Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells. Molecular Medicine Reports, 14, 5677-5684. https://doi.org/10.3892/mmr.2016.5952
MLA
Chakraborty, T. R., Cohen, J., Yohanan, D., Alicea, E., Weeks, B. S., Chakraborty, S."Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells". Molecular Medicine Reports 14.6 (2016): 5677-5684.
Chicago
Chakraborty, T. R., Cohen, J., Yohanan, D., Alicea, E., Weeks, B. S., Chakraborty, S."Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells". Molecular Medicine Reports 14, no. 6 (2016): 5677-5684. https://doi.org/10.3892/mmr.2016.5952