Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice

Yang, Yanmin; Liang, Feng; Gao, Jie; Dong, Yuanlin; Zhang, Yiying; Yang, Guang; Soriano, Sulpicio G.; Feng, Huajun; Xie, Zhongcong

doi:10.1016/j.bja.2021.08.028

Cited by 36 publications

(24 citation statements)

References 62 publications

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“…The disruption of E/I balance during the critical neurodevelopmental period is of considerable concern since E/I imbalance is an important mechanism for neurodevelopmental disorders 6 – 8 . In line with such concerns, studies that reported anesthesia-induced E/I imbalance also found long-term behavioral changes in activity, anxiety, sociability, learning, and memory 5 , 9 – 12 .…”

Section: Introductionmentioning

confidence: 74%

“…As millions of children receive anesthesia for surgical or diagnostic procedures every year, anesthesia-induced neurotoxicity in the developing brain has received considerable research interest in recent decades 1 . Preclinical studies have shown that anesthetics commonly used in clinical settings may act as neurotoxins during neurodevelopment, inducing widespread neuronal cell death or excitatory/inhibitory (E/I) imbalance 2 – 5 . The disruption of E/I balance during the critical neurodevelopmental period is of considerable concern since E/I imbalance is an important mechanism for neurodevelopmental disorders 6 – 8 .…”

Section: Introductionmentioning

confidence: 99%

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Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Cui

Lee

et al. 2022

Commun Biol

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Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg−1, 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg−1) and nicotine (0.5 mg kg−1). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life.

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Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Cui

Lee

et al. 2022

Commun Biol

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“…The latest study by Yang and colleagues has shown that exogenous administration of testosterone attenuated sevoflurane-induced cognitive impairment in male neonatal mice. Using a multitude of approaches, it was concluded that low levels of testosterone-a physiological occurrence in neonatal male pups-could be a culprit for their vulnerability to sevoflurane-induced cognitive impairment [71] as administration of exogenous testosterone to male neonatal mice reduced tau phosphorylation and prevented cognitive impairment by inhibiting the GSK-3β activation [71].…”

Section: Steroid Hormonesmentioning

confidence: 99%

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

Useinovic

Maksimovic

Near

et al. 2022

IJMS

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Since its invention, general anesthesia has been an indispensable component of modern surgery. While traditionally considered safe and beneficial in many pathological settings, hundreds of preclinical studies in various animal species have raised concerns about the detrimental and long-lasting consequences that general anesthetics may cause to the developing brain. Clinical evidence of anesthetic neurotoxicity in humans continues to mount as we continue to contemplate how to move forward. Notwithstanding the alarming evidence, millions of children are being anesthetized each year, setting the stage for substantial healthcare burdens in the future. Hence, furthering our knowledge of the molecular underpinnings of anesthesia-induced developmental neurotoxicity is crucially important and should enable us to develop protective strategies so that currently available general anesthetics could be safely used during critical stages of brain development. In this mini-review, we provide a summary of select strategies with primary focus on the mechanisms of neuroprotection and potential for clinical applicability. First, we summarize a diverse group of chemicals with the emphasis on intracellular targets and signal-transduction pathways. We then discuss epigenetic and transgenerational effects of general anesthetics and potential remedies, and also anesthesia-sparing or anesthesia-delaying approaches. Finally, we present evidence of a novel class of anesthetics with a distinct mechanism of action and a promising safety profile.

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“…However, testosterone might have dual effects on neurodevelopment. Recent studies have proposed that testosterone inhibits the interaction between microtubule-associated protein tau and glycogen synthase kinase-3β (GSK3β) to attenuate tau phosphorylation ( Yang et al, 2021 ; Jevtovic-Todorovic, 2022 ). Increased tau phosphorylation is associated with altering dendritic spines’ plasticity ( Pallas-Bazarra et al, 2016 ), which is related to long-term cognitive dysfunction.…”

Section: Preclinical Evidence: Exploring Mechanisms Of Anesthesia-ind...mentioning

confidence: 99%

Anesthesia and developing brain: What have we learned from recent studies

Niu

Jia

Jiang

2022

Front. Mol. Neurosci.

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Anesthesia is unavoidable in surgical procedures. However, whether the general anesthetics are neurotoxic to immature brains remains undefined. Neurodevelopmental impairment induced by anesthesia has been a critical health issue and topic of concern. This review summarizes recent progress made in clinical and preclinical studies to provide useful suggestions and potential therapeutic targets for the protection of the immature brain. On the one hand, clinical researchers continue the debate about the effect of single and multiple exposures to anesthesia on developing brains. On the other hand, preclinical researchers focus on exploring the mechanisms of neurotoxic effects of general anesthesia on immature brains and seeking novel solutions. Rodent models have always been used in preclinical studies, but it is still unclear whether the mechanisms observed in rodent models have clinical relevance. Compared with these models, non-human primates (NHPs) are more genetically similar to humans. However, few research institutions in this area can afford to use NHP models in their studies. One way to address both problems is by combining single-cell sequencing technologies to screen differential gene expression in NHPs and perform in vivo validation in rodents. The mechanism of anesthesia-induced neurotoxicity still requires further elucidation in primates.

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Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice

Cited by 36 publications

References 62 publications

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

Anesthesia and developing brain: What have we learned from recent studies

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