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Sexually dimorphic changes of hypocretin (orexin) in depression. / Lu, J.; Zhao, Juan; Balesar, R.A.; Fronczek, Rolf; Zhu, Q.; Wu, X.; Hu, S.H.; Bao, A.M.; Swaab, D.F.

In: EBioMedicine, Vol. 18, 31.03.2017, p. 311-319.

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Lu, J. ; Zhao, Juan ; Balesar, R.A. ; Fronczek, Rolf ; Zhu, Q. ; Wu, X. ; Hu, S.H. ; Bao, A.M. ; Swaab, D.F. / Sexually dimorphic changes of hypocretin (orexin) in depression. In: EBioMedicine. 2017 ; Vol. 18. pp. 311-319.

BibTeX

@article{51f68726848548fc9f27f6b36fd333b9,
title = "Sexually dimorphic changes of hypocretin (orexin) in depression.",
abstract = "BackgroundNeurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects.MethodsWe quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat.Resultsi) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats.ConclusionsThe clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.",
author = "J. Lu and Juan Zhao and R.A. Balesar and Rolf Fronczek and Q. Zhu and X. Wu and S.H. Hu and A.M. Bao and D.F. Swaab",
year = "2017",
month = "3",
day = "31",
doi = "10.1016/j.ebiom.2017.03.043",
language = "English",
volume = "18",
pages = "311--319",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Sexually dimorphic changes of hypocretin (orexin) in depression.

AU - Lu, J.

AU - Zhao, Juan

AU - Balesar, R.A.

AU - Fronczek, Rolf

AU - Zhu, Q.

AU - Wu, X.

AU - Hu, S.H.

AU - Bao, A.M.

AU - Swaab, D.F.

PY - 2017/3/31

Y1 - 2017/3/31

N2 - BackgroundNeurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects.MethodsWe quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat.Resultsi) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats.ConclusionsThe clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.

AB - BackgroundNeurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects.MethodsWe quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat.Resultsi) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats.ConclusionsThe clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.

U2 - 10.1016/j.ebiom.2017.03.043

DO - 10.1016/j.ebiom.2017.03.043

M3 - Article

VL - 18

SP - 311

EP - 319

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -

ID: 4083884