In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats

Burcu Sırmatel Bakrıyanık; Çiğdem Özer; Cemile Merve Seymen

doi:10.4274/atfm.galenos.2025.78608

EN TR

In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats

Abstract

Objectives: Previous in vitro studies have demonstrated that brain-derived neurotrophic factor (BDNF) modulates α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) expression and the trafficking of synaptic AMPA receptors (AMPARs). However, it is not known whether exogenous BDNF administration similarly regulates AMPAR trafficking in vivo. This study aims to elucidate this unknown aspect. Additionally, considering that BDNF and estrogen have similar effects in the brain and may interact through their cellular mechanisms, the study also aims to explore the outcomes of BDNF administration in female rats. Material and Methods: For this purpose, female Long-Evans rats in the same estrus phase were divided into the experimental group (EG, n=5) and the control group (CG, n=5). In the EG, recombinant BDNF protein (4 μg/day) was administered to the right hippocampus via osmotic minipumps for 7 days, while the CG received phosphate-buffered saline (PBS) (4 μg/day) under the same conditions. The Morris Water Maze (MWM) test was employed for assessing learning and memory. AMPAR levels in the left and right hippocampi were examined using immunohistochemical methods, and the intensity patterns were evaluated using H-scoring. Results: Although no significant behavioral differences were observed between the groups in the MWM task (p>0.05), H-scoring results revealed that BDNF treatment significantly increased GluR1 subunit immunoreactivity in the right hippocampus of the EG compared to the CG (p≤0.001). Notably, GluR1 H-score levels were also significantly increased in the left hemisphere, which was not directly infused with BDNF. Conclusion: This study demonstrates that long-term BDNF administration increases AMPAR levels in the hippocampus in vivo. While this increase has behavioral implications for spatial learning and memory in female rats, further research is needed to explore the full extent of these effects.

Keywords

AMPA receptor, long-term potentiation, brain-derived neurotrophic factor, learning and memory, synaptic plasticity

Eksojen BDNF Uygulamasının Dişi Sıçan Dentat Girus AMPA Reseptörüne In Vivo Etkisi

Abstract

Amaç: Önceki in vitro araştırmalar, beyin türevli nörotrofik faktörün (BDNF) α-amino-3-hidroksi-5-metil-4-izoksazol propiyonik asit (AMPA) ekspresyonunu ve sinaptik AMPA reseptörlerinin (AMPAR) trafiğini modüle ettiğini göstermiştir. Ancak, eksojen BDNF uygulamasının in vivo ortamda AMPAR trafiğini benzer şekilde düzenleyip düzenlemediği bilinmemektedir. Bu çalışma, bu bilinmeyeni aydınlatmayı amaçlamaktadır. Ayrıca BDNF ve östrojenin beyinde benzer etkilere sebep olması ve hücresel mekanizmalarının birbirini etkilemesi nedeniyle dişilere BDNF uygulamanın sonuçlarını gözlemlemek de hedeflenmiştir. Gereç ve Yöntem: Aynı estrus evresindeki dişi Long-Evans sıçanları, deney grubu (DG, n=5) kontrol grubu (KG, n=5) olarak ayrılmıştır. DG sağ hipokampüslerine BDNF proteini (4 μg/gün), KG grubu sıçanlarınkine ise PBS (4 μg/gün), ozmotik minipompalar vasıtasıyla intrahipokampal olarak Bulgular: Genel olarak davranış deneyi açısından gruplar arasında anlamlı farklılık gözlenmemesine rağmen H-skor sonuçlarına göre BDNF uygulaması DG’nin sağ (p≤0,001) hipokampusunda KG’ye kıyasla AMPAR alt birimi GluR1’in immünoreaktivitesini önemli ölçüde artırmıştır. Hatta GluR1 H-skor seviyeleri infüzyon alanı olmayan sol hemisferde de anlamlı olarak yükselmiştir (p≤0,001). Sonuç: Bu çalışma, uzun süreli BDNF uygulamasının hipokampusta AMPAR seviyelerini artırdığını in vivo olarak göstermektedir. Bu artışın dişi sıçanlardaki mekansal öğrenme ve bellek sürecine davranışsal yansımaları olmakla birlikte anlamlı etkileri için ileri araştırmalara ihtiyaç duyulmaktadır.

Keywords

AMPA reseptörü, uzun-dönem potansiyasyon, beyin türevli nörotrofik faktör, öğrenme ve bellek, sinaptik plastisite

Ethical Statement

Ethics Committee Approval: This study was approved by the Gazi University Local Ethics Committee for Animal Experiments (decision no: E.28661, date: 16.08.2017). Informed Consent: In this study, we utilized adult female Long-Evans rats (n=10), each weighing between 200-250 g. The animals were obtained from the Gazi University Laboratory Animals Breeding and Experimental Research Center (GUDAM). All procedures involving the rats were conducted in the designated laboratory settings of GUDAM. Acknowledgments We would like to thank the expert and staff members at the Gazi University Laboratory Animal Breeding and Experimental Research Center. We also extend our gratitude to young researcher Batuhan Sözer for his contributions in preparing Python code for data analysis from the video recordings of the MWM task, which facilitated a detailed examination of this aspect of the study. Footnotes Authorship Contributions Surgical and Medical Practices: B.S.B., Concept: B.S.B., Ç.Ö., Design: B.S.B., Ç.Ö., Data Collection and/or Processing: B.S.B., C.M.S., Analysis and/or Interpretation: B.S.B., Ç.Ö., C.M.S., Literature Search: B.S.B., Ç.Ö., Writing: B.S.B., C.M.S. Conflict of Interest: The authors have no conflicts of interest to declare. Financial Disclosure: This study is supported by the Gazi University Scientific Research Projects Coordination Unit with the decision number 01/2017-26.

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Details

Primary Language

English

Subjects

Computational Neuroscience

Journal Section

Research Article

Authors

Burcu Sırmatel Bakrıyanık ^* This is me
0000-0002-8061-2618
Türkiye

Çiğdem Özer This is me
0000-0002-2705-4522
Türkiye

Cemile Merve Seymen
0000-0002-8945-3801
Türkiye

Publication Date

July 1, 2025

Submission Date

April 1, 2025

Acceptance Date

June 30, 2025

Published in Issue

Year 2025 Volume: 78 Number: 2

DOI

https://doi.org/10.4274/atfm.galenos.2025.78608

IZ

https://izlik.org/JA53BL44HH

APA

Sırmatel Bakrıyanık, B., Özer, Ç., & Seymen, C. M. (2025). In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 78(2), 93-105. https://doi.org/10.4274/atfm.galenos.2025.78608

AMA

1.Sırmatel Bakrıyanık B, Özer Ç, Seymen CM. In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2025;78(2):93-105. doi:10.4274/atfm.galenos.2025.78608

Chicago

Sırmatel Bakrıyanık, Burcu, Çiğdem Özer, and Cemile Merve Seymen. 2025. “In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78 (2): 93-105. https://doi.org/10.4274/atfm.galenos.2025.78608.

EndNote

Sırmatel Bakrıyanık B, Özer Ç, Seymen CM (July 1, 2025) In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78 2 93–105.

IEEE

[1]B. Sırmatel Bakrıyanık, Ç. Özer, and C. M. Seymen, “In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 78, no. 2, pp. 93–105, July 2025, doi: 10.4274/atfm.galenos.2025.78608.

ISNAD

Sırmatel Bakrıyanık, Burcu - Özer, Çiğdem - Seymen, Cemile Merve. “In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 78/2 (July 1, 2025): 93-105. https://doi.org/10.4274/atfm.galenos.2025.78608.

JAMA

1.Sırmatel Bakrıyanık B, Özer Ç, Seymen CM. In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2025;78:93–105.

MLA

Sırmatel Bakrıyanık, Burcu, et al. “In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 78, no. 2, July 2025, pp. 93-105, doi:10.4274/atfm.galenos.2025.78608.

Vancouver

1.Burcu Sırmatel Bakrıyanık, Çiğdem Özer, Cemile Merve Seymen. In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2025 Jul. 1;78(2):93-105. doi:10.4274/atfm.galenos.2025.78608

In Vivo Effects of Exogenous BDNF Administration on AMPA Receptors in the Dentate Gyrus of Female Rats

Abstract

Keywords

Eksojen BDNF Uygulamasının Dişi Sıçan Dentat Girus AMPA Reseptörüne In Vivo Etkisi

Abstract

Keywords

Ethical Statement

References

Details

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