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Aquaporin 4 and 1 Expression Changes in the Brain of Pinealectomized Rats: Role of Melatonin

Yıl 2024, Cilt: 12 Sayı: 2, 702 - 722, 20.06.2024
https://doi.org/10.33715/inonusaglik.1463177

Öz

The brain's glymphatic system, a fluid exchange system, is associated with the aquaporin 4 (AQP4) water channels in astrocytes and aquaporin 1 (AQP1) in the ventricular choroid plexus. Circadian rhythms have also been reported to maintain fluid homeostasis in the brain. In this study, we aimed to determine the relationship between melatonin (pinealectomy and exogenous melatonin supplementation), which regulates circadian rhythm, and AQP4 and AQP1. The study, 50 male rats were divided into five groups (n=10). The groups were determined as Control, Sham Pinealectomy (Sham PX), Melatonin (MEL), Pinealectomy (PX), and PX+MEL. The MEL group received intraperitoneal injection of MEL (10 mg/kg/day) for 30 days, and the PX group received only PX surgery. We examined changes in AQP1 and AQP4 expression in brain tissue after PX surgery (MEL deprivation) and MEL injections. While there was no statistically significant difference in AQP1 and AQP4 levels between the control and Sham PX groups, a significant decrease was observed in the PX group (p<0.001). While an increase in AQP4 level was observed in the PX+MEL group (p<0.001), the AQP1 level did not change. This study demonstrated that MEL significantly contributed to the glymphatic system via AQP4 but not AQP1.

Kaynakça

  • Abbott, N. J., Pizzo, M. E., Preston, J. E., Janigro, D.ve Thorne, R. G. (2018). The role of brain barriers in fluid movement in the CNS: Is there a ‘glymphatic’system? Acta neuropathologica, 135(3), 387-407.
  • Akdemir, G., Kaymaz, F., Gursoy-Özdemir, Y., Akalan, N. ve Akdemir, E. S. (2016). The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat. Surgical Neurology International, 7.
  • Arciénega, I., Brunet, J., Bloch, J. ve Badaut, J. (2010). Cell locations for AQP1, AQP4 and 9 in the non-human primate brain. Neuroscience, 167(4), 1103-1114.
  • Bèchet, N. B., Shanbhag, N. C. ve Lundgaard, I. (2021). Glymphatic pathways in the gyrencephalic brain. Journal of Cerebral Blood Flow & Metabolism, 41(9), 2264-2279.
  • Bonsall, D. R. ve Lall, G. S. (2013). Protein kinase C differentially regulates entrainment of the mammalian circadian clock. Chronobiology International, 30(4), 460-469.
  • Channels, I. A. W. (2005). Physiological roles of aquaporins in the choroid plexus. Current topics in Developmental Biology, 67, 181.
  • Chong, P. L., Garic, D., Shen, M. D., Lundgaard, I. ve Schwichtenberg, A. J. (2022). Sleep, cerebrospinal fluid, and the glymphatic system: A systematic review. Sleep Medicine Reviews, 61, 101572.
  • De Laurentis, C., Cristaldi, P., Arighi, A., Cavandoli, C., Trezza, A., Sganzerla, E. P., …Di Cristofori, A. (2021). Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review. Journal of Neurology, 268, 4078-4094.
  • Demiral, Ş. B., Tomasi, D., Sarlls, J., Lee, H., Wiers, C. E., Zehra, A., …Freeman, C. R. (2019). Apparent diffusion coefficient changes in human brain during sleep–Does it inform on the existence of a glymphatic system? Neuroimage, 185, 263-273.
  • Feng, X., Papadopoulos, M. C., Liu, J., Li, L., Zhang, D., Zhang, H., …Ma, T. (2009). Sporadic obstructive hydrocephalus in Aqp4 null mice. Journal Of Neuroscience Research, 87(5), 1150-1155.
  • Filippidis, A. S., Carozza, R. B. ve Rekate, H. L. (2016). Aquaporins in brain edema and neuropathological conditions. International Journal of Molecular Sciences, 18(1), 55.
  • Gheban, B.-A., Colosi, H. A., Gheban-Rosca, I.-A., Pop, B., Domșa, A.-M. T., Georgiu, C., …Crișan, M. (2021). Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies. Medicina (B Aires), 57(4), 383.
  • Goldman, N., Hablitz, L. M., Mori, Y. ve Nedergaard, M. (2020). The glymphatic system and pain. Medical Acupuncture, 32(6), 373-376.
  • Gomolka, R. S., Hablitz, L. M., Mestre, H., Giannetto, M., Du, T., Hauglund, N. L., ….Nedergaard, M. (2023). Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation. Elife, 12, e82232.
  • Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., …Nedergaard, M. (2020a). Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun, 11(1), 1-11.
  • Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., ….Nedergaard, M. (2020b). Circadian control of brain glymphatic and lymphatic fluid flow. Nature Communications, 11(1), 4411.
  • Han, G., Zhou, Y., Zhang, K., Jiao, B., Hu, J., Zhang, Y., …Bai, R. (2023). Age-and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods. Frontiers in Aging Neuroscience, 15, 1173221.
  • Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., …Goldman, S. A. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science Translational Medicine, 4(147), 147ra111-147ra111.
  • J Reiter, R., Tan, D.-X., Rosales-Corral, S. ve C Manchester, L. (2013). The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Rev Med Chem, 13(3), 373-384.
  • Jessen, N. A., Munk, A. S. F., Lundgaard, I. ve Nedergaard, M. (2015). The glymphatic system: a beginner’s guide. Neurochemical Research, 40(12), 2583-2599.
  • Kim, J. G., Son, Y. J., Yun, C. H., Kim, Y. I., Nam-Goong, I. S., Park, J. H., …Damante, G. (2007). Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain. Journal of Biological Chemistry, 282(20), 14923-14931.
  • King, L. S.ve Agre, P. (1996). Pathophysiology of the aquaporin water channels. Annual Review of Physiology, 58(1), 619-648.
  • Legros, C., Chesneau, D., Boutin, J. A., Barc, C. ve Malpaux, B. (2014). Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions. Journal of Neuroendocrinology, 26(3), 151-163.
  • Li, W., Chen, D., Liu, N., Luan, Y., Zhu, S.ve Wang, H. (2022). Modulation of lymphatic transport in the central nervous system. Theranostics, 12(3), 1117.
  • Liu, X., Hao, J., Yao, E., Cao, J., Zheng, X., Yao, D., …Luo, X. (2020). Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems. Brain, Behavior, and Immunity, 89, 357-370.
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PİNEALEKTOMİZE SIÇANLARIN BEYNİNDE AKUAPORİN 4 VE 1 EKSPRESYON DEĞİŞİKLİKLERİ: MELATONİNİN ROLÜ

Yıl 2024, Cilt: 12 Sayı: 2, 702 - 722, 20.06.2024
https://doi.org/10.33715/inonusaglik.1463177

Öz

Beyinde bir sıvı değişim sistemi olan glenfatik sistem, astrositlerde akuaporin 4 (AQP4) ve ventriküler koroid pleksusta akuaporin 1 (AQP1) su kanalları ile ilişkilidir. Ayrıca beyinde sıvı homeostazının sürdürülmesinde sirkadiyen ritimlerin varlığı bildirilmiştir. Bu çalışmada sirkadiyen ritmi düzenleyen melatonin (pinealektomi ve eksojen melatonin takviyesi) ile AQP4 ve AQP1 arasındaki ilişkinin belirlenmesi amaçlanmıştır. Bu çalışmada 50 adet erkek sıçan beş gruba ayrıldı. Gruplar; Kontrol, Sham Pinealektomi (Sham PX), Melatonin (MEL), Pinealektomi (PX), PX+MEL olarak belirlendi. MEL grubuna 30 gün intraperitoneal MEL (10 mg/kg/gün) enjeksiyonu, PX grubuna ise sadece PX cerrahisi uygulandı. PX cerrahisi (MEL yoksunluğu) ve MEL enjeksiyonlarından sonra beyin dokusunda AQP1 ve AQP4 ifadelerindeki değişiklikler incelendi. AQP1 ve AQP4 seviyelerinde kontrol ve Sham PX grupları arasında istatistiksel olarak anlamlı bir fark yokken, PX grubunda anlamlı derecede bir azalma gözlenmiştir (p<0.001). PX+MEL grubunda AQP4 seviyesinde artış gözlenirken (p<0.001), AQP1 seviyesinin değişmediği tespit edilmiştir. Bu çalışma MEL’in AQP4 aracılığı ile glenfatik sisteme önemli katkı sağladığını ancak bu katkıyı AQP1 ile sağlayamadığını göstermiştir.

Etik Beyan

Çalışma Karabük Üniversitesi Tıp Fakültesi Deney Hayvanları Etik Kurulu onayı ile gerçekleştirilmiştir (Tarih: 21/04/2022, Karar numarası: 2022/4/7, Kayıt numarası: E-55212866-050.99-125555). Tüm deneysel prosedürler, deney hayvanlarının kullanımına ilişkin Hayvan Etik Kurulu Yönergesine uygun olarak gerçekleştirilmiştir.

Destekleyen Kurum

Bu proje Karabük Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi tarafından desteklenmiştir (KBÜBAP-22-KP-144).

Kaynakça

  • Abbott, N. J., Pizzo, M. E., Preston, J. E., Janigro, D.ve Thorne, R. G. (2018). The role of brain barriers in fluid movement in the CNS: Is there a ‘glymphatic’system? Acta neuropathologica, 135(3), 387-407.
  • Akdemir, G., Kaymaz, F., Gursoy-Özdemir, Y., Akalan, N. ve Akdemir, E. S. (2016). The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat. Surgical Neurology International, 7.
  • Arciénega, I., Brunet, J., Bloch, J. ve Badaut, J. (2010). Cell locations for AQP1, AQP4 and 9 in the non-human primate brain. Neuroscience, 167(4), 1103-1114.
  • Bèchet, N. B., Shanbhag, N. C. ve Lundgaard, I. (2021). Glymphatic pathways in the gyrencephalic brain. Journal of Cerebral Blood Flow & Metabolism, 41(9), 2264-2279.
  • Bonsall, D. R. ve Lall, G. S. (2013). Protein kinase C differentially regulates entrainment of the mammalian circadian clock. Chronobiology International, 30(4), 460-469.
  • Channels, I. A. W. (2005). Physiological roles of aquaporins in the choroid plexus. Current topics in Developmental Biology, 67, 181.
  • Chong, P. L., Garic, D., Shen, M. D., Lundgaard, I. ve Schwichtenberg, A. J. (2022). Sleep, cerebrospinal fluid, and the glymphatic system: A systematic review. Sleep Medicine Reviews, 61, 101572.
  • De Laurentis, C., Cristaldi, P., Arighi, A., Cavandoli, C., Trezza, A., Sganzerla, E. P., …Di Cristofori, A. (2021). Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review. Journal of Neurology, 268, 4078-4094.
  • Demiral, Ş. B., Tomasi, D., Sarlls, J., Lee, H., Wiers, C. E., Zehra, A., …Freeman, C. R. (2019). Apparent diffusion coefficient changes in human brain during sleep–Does it inform on the existence of a glymphatic system? Neuroimage, 185, 263-273.
  • Feng, X., Papadopoulos, M. C., Liu, J., Li, L., Zhang, D., Zhang, H., …Ma, T. (2009). Sporadic obstructive hydrocephalus in Aqp4 null mice. Journal Of Neuroscience Research, 87(5), 1150-1155.
  • Filippidis, A. S., Carozza, R. B. ve Rekate, H. L. (2016). Aquaporins in brain edema and neuropathological conditions. International Journal of Molecular Sciences, 18(1), 55.
  • Gheban, B.-A., Colosi, H. A., Gheban-Rosca, I.-A., Pop, B., Domșa, A.-M. T., Georgiu, C., …Crișan, M. (2021). Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies. Medicina (B Aires), 57(4), 383.
  • Goldman, N., Hablitz, L. M., Mori, Y. ve Nedergaard, M. (2020). The glymphatic system and pain. Medical Acupuncture, 32(6), 373-376.
  • Gomolka, R. S., Hablitz, L. M., Mestre, H., Giannetto, M., Du, T., Hauglund, N. L., ….Nedergaard, M. (2023). Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation. Elife, 12, e82232.
  • Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., …Nedergaard, M. (2020a). Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun, 11(1), 1-11.
  • Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., ….Nedergaard, M. (2020b). Circadian control of brain glymphatic and lymphatic fluid flow. Nature Communications, 11(1), 4411.
  • Han, G., Zhou, Y., Zhang, K., Jiao, B., Hu, J., Zhang, Y., …Bai, R. (2023). Age-and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods. Frontiers in Aging Neuroscience, 15, 1173221.
  • Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., …Goldman, S. A. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science Translational Medicine, 4(147), 147ra111-147ra111.
  • J Reiter, R., Tan, D.-X., Rosales-Corral, S. ve C Manchester, L. (2013). The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Rev Med Chem, 13(3), 373-384.
  • Jessen, N. A., Munk, A. S. F., Lundgaard, I. ve Nedergaard, M. (2015). The glymphatic system: a beginner’s guide. Neurochemical Research, 40(12), 2583-2599.
  • Kim, J. G., Son, Y. J., Yun, C. H., Kim, Y. I., Nam-Goong, I. S., Park, J. H., …Damante, G. (2007). Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain. Journal of Biological Chemistry, 282(20), 14923-14931.
  • King, L. S.ve Agre, P. (1996). Pathophysiology of the aquaporin water channels. Annual Review of Physiology, 58(1), 619-648.
  • Legros, C., Chesneau, D., Boutin, J. A., Barc, C. ve Malpaux, B. (2014). Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions. Journal of Neuroendocrinology, 26(3), 151-163.
  • Li, W., Chen, D., Liu, N., Luan, Y., Zhu, S.ve Wang, H. (2022). Modulation of lymphatic transport in the central nervous system. Theranostics, 12(3), 1117.
  • Liu, X., Hao, J., Yao, E., Cao, J., Zheng, X., Yao, D., …Luo, X. (2020). Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems. Brain, Behavior, and Immunity, 89, 357-370.
  • Livak, K. J. ve Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402-408.
  • Mack, A. F., Bihlmaier, R. ve Deffner, F. (2023). Shifting from ependyma to choroid plexus epithelium and the changing expressions of aquaporin‐1 and aquaporin‐4. The Journal of Physiology, 1-14.
  • Magdoom, K. N., Brown, A., Rey, J., Mareci, T. H., King, M. A. ve Sarntinoranont, M. (2019). MRI of whole rat brain perivascular network reveals role for ventricles in brain waste clearance. Sci Rep, 9(1), 1-11.
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  • Papadopoulos, M. C., Manley, G. T., Krishna, S. ve Verkman, A. (2004). Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edema. The FASEB Journal, 18(11), 1291-1293.
  • Paulose, J. K., Peters, J. L., Karaganis, S. P. ve Cassone, V. M. (2009). Pineal melatonin acts as a circadian zeitgeber and growth factor in chick astrocytes. Journal of Pineal Research, 46(3), 286-294.
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  • Quintela, T., Furtado, A., Duarte, A. C., Gonçalves, I., Myung, J. ve Santos, C. R. (2021). The role of circadian rhythm in choroid plexus functions. Prog Neurobiol, 205, 102129.
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  • Yamaguchi, T., Hamada, T., Matsuzaki, T. ve Iijima, N. (2020). Characterization of the circadian oscillator in the choroid plexus of rats. Biochem Biophys Res Commun, 524(2), 497-501.
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Toplam 69 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Geleneksel, Tamamlayıcı ve Bütünleştirici Tıp (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Demir 0000-0001-6990-3337

Feyza Başak 0000-0002-9335-1103

Erken Görünüm Tarihi 3 Haziran 2024
Yayımlanma Tarihi 20 Haziran 2024
Gönderilme Tarihi 1 Nisan 2024
Kabul Tarihi 21 Mayıs 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 12 Sayı: 2

Kaynak Göster

APA Demir, M., & Başak, F. (2024). PİNEALEKTOMİZE SIÇANLARIN BEYNİNDE AKUAPORİN 4 VE 1 EKSPRESYON DEĞİŞİKLİKLERİ: MELATONİNİN ROLÜ. İnönü Üniversitesi Sağlık Hizmetleri Meslek Yüksek Okulu Dergisi, 12(2), 702-722. https://doi.org/10.33715/inonusaglik.1463177