Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.
The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure.
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Liang
L
Zhong
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China. lfqjxmc@outlook.com.
Foquan
F
Luo
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Weilu
W
Zhao
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Yunlin
Y
Feng
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Liuqin
L
Wu
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Jiamei
J
Lin
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Tianyin
T
Liu
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Shengqiang
S
Wang
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Xuexue
X
You
Department of Anesthesiology, The First Affiliated Hospital, Nanchang University, Nancahang, China.
Wei
W
Zhang
D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D047309:Flavones / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology*; D015742:Propofol / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016708:Synaptophysin
C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D047309:Flavones; D016708:Synaptophysin; D020813:Receptor, trkB; D015742:Propofol
7,8-dihydroxyflavone; BDNF-TrkB signal pathway; late pregnancy; learning and memory; offspring; propofol; synaptophysin