Hippocampal SIRT1-Mediated Synaptic Plasticity and Glutamatergic Neuronal Excitability Are Involved in Prolonged Cognitive Dysfunction of Neonatal Rats Exposed to Propofol

• Published in: Molecular neurobiology Vol. 59; no. 3; pp. 1938 - 1953
• Main Authors: Ma, Lin-Hui, Wan, Jie, Yan, Jing, Wang, Ning, Liu, Yan-Ping, Wang, Hai-Bi, Zhou, Cheng-Hua, Wu, Yu-Qing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2022; Springer Nature B.V
• Subjects: Anesthesia; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cognitive ability; Cognitive Dysfunction - metabolism; Excitability; Glutamatergic transmission; Hippocampal plasticity; Hippocampus; Hippocampus - metabolism; Immunofluorescence; Learning; Maze Learning; Memory; Neonates; Neurobiology; Neurology; Neuronal Plasticity; Neurons - metabolism; Neurosciences; Propofol; Propofol - pharmacology; Rats; Rats, Sprague-Dawley; SIRT1 protein; Sirtuin 1 - metabolism; Synaptic plasticity; Western blotting; Optogenetics; Propofol; Cognitive function; SIRT1; Excitation-inhibition imbalance; Synaptic plasticity
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-021-02684-4

Neonates who receive repeated or prolonged general anesthesia before the age of 4 are at a significantly higher risk of developing cognitive dysfunction later in life. In this study, we investigated the effects of repeated neonatal propofol exposure on hippocampal synaptic plasticity, neuronal excitability, and cognitive function. Adeno-associated SIRT1 virus with CaMKIIɑ promotor and a viral vector carrying the photosensitive gene ChR2 with the CaMKIIɑ promotor, as well as their control vectors, were stereotaxically injected into the hippocampal CA1 region of postnatal day 5 (PND-5) rats. PND-7 rats were given intraperitoneal injection of 60 mg/kg propofol or fat emulsion for three consecutive days. Western blotting, Golgi staining, and double immunofluorescence staining were used to evaluate the SIRT1 expression, synaptic plasticity, and the excitability of neurons in the hippocampal CA1 region. The Morris water maze (MWM) test was conducted on PND-30 to assess the learning and memory abilities of rats. Repeated neonatal propofol exposure reduced SIRT1 expression, suppressed synaptic plasticity, decreased glutamatergic neuron excitability in the hippocampus, and damaged learning and memory abilities. Overexpression of SIRT1 attenuated propofol-induced cognitive dysfunction, excitation-inhibition imbalance, and synaptic plasticity damage. After optogenetic stimulation of glutamatergic neurons in the hippocampal CA1 region, the learning and memory abilities of rats exposed to propofol were improved on PND-30. Our findings demonstrate that SIRT1 plays an important role in cognitive dysfunction induced by repeated neonatal propofol exposure by suppressing synaptic plasticity and neuronal excitability.