Int Neurourol J.  2019 Jun;23(2):116-124. 10.5213/inj.1938103.052.

Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus

Affiliations
  • 1School of Global Sport Studies, Korea University, Sejong, Korea.
  • 2Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 3Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Korean Medicine, Kyung Hee University, Seoul, Korea.
  • 4Department of Exercise Rehabilitation and Welfare, College of Health Science, Gachon University, Incheon, Korea.
  • 5Department of Urology, Gachon University School of Medicine, Gil Medical Center, Incheon, Korea. kimcho99@gilhospital.com, shinekkt@gmail.com

Abstract

PURPOSE
Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal-regulated kinases (MEK)/extracellular signal-regulated kinases (ERK) pathways in the hippocampus.
METHODS
Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used.
RESULTS
The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups.
CONCLUSIONS
Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

Keyword

Castration; Memory; Neurogenesis

MeSH Terms

Abdominal Wall
Adenosine Monophosphate
Blotting, Western
Castration*
Cyclic AMP-Dependent Protein Kinases
Down-Regulation*
Goserelin
Hippocampus*
Immunohistochemistry
Memory*
Memory, Short-Term
Models, Animal
Neurogenesis
Orchiectomy
Phosphorylation
Phosphotransferases
Spatial Memory
Adenosine Monophosphate
Cyclic AMP-Dependent Protein Kinases
Goserelin
Phosphotransferases
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