抄録
Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na+] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na+] was < 125 mEq/L (moderate hyponatremia), but rarely in those whose serum [Na+] was ≥ 125 mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7 days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 65-74 |
| ページ数 | 10 |
| ジャーナル | Experimental Neurology |
| 巻 | 287 |
| DOI | |
| 出版物ステータス | Published - 01-01-2017 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Developmental Neuroscience
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NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats. / Izumida, Hisakazu; Takagi, Hiroshi; Fujisawa, Haruki; Iwata, Naoko; Nakashima, Kohtaro; Takeuchi, Seiji; Iwama, Shintaro; Namba, Takashi; Komatu, Yukio; Kaibuchi, Kozo; Oiso, Yutaka; Arima, Hiroshi; Sugimura, Yoshihisa.
：: Experimental Neurology, 巻 287, 01.01.2017, p. 65-74.研究成果: Article
TY - JOUR
T1 - NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats
AU - Izumida, Hisakazu
AU - Takagi, Hiroshi
AU - Fujisawa, Haruki
AU - Iwata, Naoko
AU - Nakashima, Kohtaro
AU - Takeuchi, Seiji
AU - Iwama, Shintaro
AU - Namba, Takashi
AU - Komatu, Yukio
AU - Kaibuchi, Kozo
AU - Oiso, Yutaka
AU - Arima, Hiroshi
AU - Sugimura, Yoshihisa
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na+] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na+] was < 125 mEq/L (moderate hyponatremia), but rarely in those whose serum [Na+] was ≥ 125 mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7 days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients.
AB - Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na+] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na+] was < 125 mEq/L (moderate hyponatremia), but rarely in those whose serum [Na+] was ≥ 125 mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7 days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients.
UR - http://www.scopus.com/inward/record.url?scp=84982095000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84982095000&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2016.08.007
DO - 10.1016/j.expneurol.2016.08.007
M3 - Article
C2 - 27527984
AN - SCOPUS:84982095000
VL - 287
SP - 65
EP - 74
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -