Repeated exposure to propofol in the neonatal period impairs hippocampal synaptic plasticity and the recognition function of rats in adulthood

Wan, Jie; Shen, Chu-Meng; Wang, Yu; Wu, Qing-Zi; Wang, Yilei; Liu, Qiang; Sun, Yi-Man; Cao, Junping; Wu, Yuqing

doi:10.1016/j.brainresbull.2021.01.007

Cited by 29 publications

(29 citation statements)

References 42 publications

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“…However, the hippocampus (HP), a key cortical structure regulating cognitive processes such as learning and memory (Broadbent et al, 2004 ; Kumaran and Maguire, 2005 ; Hannula et al, 2013 ) also resulted affected in BBSOAS patients. Due to the central role of the HP in controlling key cognitive skills, even small developmental defects can have a dramatic impact on behavioral performances (Mátéffyová et al, 2006 ; Ramos, 2008 ; Wan et al, 2021 ; Zhao et al, 2021 ). While the dorsal hippocampal pole is more involved in spatial navigation (Moser et al, 1995 ), the ventral one controls non-spatial learning and emotional behaviors (Kheirbek et al, 2013 ; Wang et al, 2013 ).…”

Section: Beyond the Neocortex: Nr2f1 Regulates The Anatomical And Functional Development Of The Hippocampusmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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The assembly and maturation of the mammalian brain result from an intricate cascade of highly coordinated developmental events, such as cell proliferation, migration, and differentiation. Any impairment of this delicate multi-factorial process can lead to complex neurodevelopmental diseases, sharing common pathogenic mechanisms and molecular pathways resulting in multiple clinical signs. A recently described monogenic neurodevelopmental syndrome named Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is caused by NR2F1 haploinsufficiency. The NR2F1 gene, coding for a transcriptional regulator belonging to the steroid/thyroid hormone receptor superfamily, is known to play key roles in several brain developmental processes, from proliferation and differentiation of neural progenitors to migration and identity acquisition of neocortical neurons. In a clinical context, the disruption of these cellular processes could underlie the pathogenesis of several symptoms affecting BBSOAS patients, such as intellectual disability, visual impairment, epilepsy, and autistic traits. In this review, we will introduce NR2F1 protein structure, molecular functioning, and expression profile in the developing mouse brain. Then, we will focus on Nr2f1 several functions during cortical development, from neocortical area and cell-type specification to maturation of network activity, hippocampal development governing learning behaviors, assembly of the visual system, and finally establishment of cortico-spinal descending tracts regulating motor execution. Whenever possible, we will link experimental findings in animal or cellular models to corresponding features of the human pathology. Finally, we will highlight some of the unresolved questions on the diverse functions played by Nr2f1 during brain development, in order to propose future research directions. All in all, we believe that understanding BBSOAS mechanisms will contribute to further unveiling pathophysiological mechanisms shared by several neurodevelopmental disorders and eventually lead to effective treatments.

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Section: Beyond the Neocortex: Nr2f1 Regulates The Anatomical And Functional Development Of The Hippocampusmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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“…Our study consisted of a cell line culture, which may have prevented us from investigating the actual effects of propofol on neurons. Second, we used cell death as the final endpoint; however, propofol may adversely affect surviving neurons that in turn affect cell function, such as disrupt the differentiation of NSCs [ 20 ] and impair hippocampal synaptic plasticity [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA BDNF-AS Attenuates Propofol-Induced Apoptosis in HT22 Cells by Modulating the BDNF/TrkB Pathway

Luo

Cao

et al. 2022

Mol Neurobiol

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Propofol is widely used as an intravenous anesthetic in clinical practice. Previous studies have indicated that propofol induces apoptosis in neurons. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, is associated with neuronal apoptosis. BDNF-AS, a relatively conserved long non-coding RNA, can reverse the transcription of BDNF. This study aimed to investigate the involvement of BDNF-AS in propofol-induced apoptosis in HT22 cells. HT22 cells were treated with various concentrations of propofol at different time points. BDNF-AS was silenced using BDNF-AS-targeting siRNA. TrkB was antagonized by the TrkB inhibitor, ANA-12. Flow cytometry, quantitative reverse-transcription PCR, and western blotting were performed to analyze apoptosis and the expression of genes and proteins, respectively. In propofol-treated HT22 cells, BDNF-AS was upregulated, and BDNF was downregulated in a time- and dose-dependent manner. BDNF-AS downregulation mediated by siRNA mitigated apoptosis, upregulated the expression of Bcl-2, and downregulated the expression of Bax and caspase-3, 7, and 9. ANA-12 downregulated the expression of Bcl-2, upregulated the expression of Bax and caspase-3, 7, and 9, and increased apoptosis. Our study implied that inhibition of BDNF-AS can decrease propofol-induced apoptosis by activating the BDNF/TrkB pathway. Thus, the BDNF-AS-BDNF/TrkB signaling pathway may be a valuable target for treating propofol-induced neurotoxicity.

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“…Since these mitochondria also are significantly larger than those in controls, it was proposed that anesthesia-induced mitochondrial enlargement causes mitochondria to be sluggish and 'stuck' in more proximal cellular compartments, thus shifting their regional distribution away from very distant thin and highly arborized dendritic branches at a time when their presence is necessary for normal synapse formation and development. In fact, we and others have reported that anesthesia impairs plasticity of dendritic spines and the formation, stability, and function of developing synapses [24][25][26][27][28][29]. Moreover, morphological distortion and impaired regional distribution of mitochondria results in mitochondriainduced reactive oxygen species upregulation, lipid peroxidation, and neuronal deletion, which may contribute to the observed impairment of synapses and neuronal network formation, ultimately leading to functional impairments [30].…”

Section: General Anesthesia and Neurodevelopmentmentioning

confidence: 99%

General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action

Maksimovic

Useinovic

Quillinan

et al. 2022

IJMS

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Over the past three decades, we have been grappling with rapidly accumulating evidence that general anesthetics (GAs) may not be as innocuous for the young brain as we previously believed. The growing realization comes from hundreds of animal studies in numerous species, from nematodes to higher mammals. These studies argue that early exposure to commonly used GAs causes widespread apoptotic neurodegeneration in brain regions critical to cognition and socio-emotional development, kills a substantial number of neurons in the young brain, and, importantly, results in lasting disturbances in neuronal synaptic communication within the remaining neuronal networks. Notably, these outcomes are often associated with long-term impairments in multiple cognitive-affective domains. Not only do preclinical studies clearly demonstrate GA-induced neurotoxicity when the exposures occur in early life, but there is a growing body of clinical literature reporting similar cognitive-affective abnormalities in young children who require GAs. The need to consider alternative GAs led us to focus on synthetic neuroactive steroid analogues that have emerged as effective hypnotics, and analgesics that are apparently devoid of neurotoxic effects and long-term cognitive impairments. This would suggest that certain steroid analogues with different cellular targets and mechanisms of action may be safe alternatives to currently used GAs. Herein we summarize our current knowledge of neuroactive steroids as promising novel GAs.

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Repeated exposure to propofol in the neonatal period impairs hippocampal synaptic plasticity and the recognition function of rats in adulthood

Cited by 29 publications

References 42 publications

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

lncRNA BDNF-AS Attenuates Propofol-Induced Apoptosis in HT22 Cells by Modulating the BDNF/TrkB Pathway

General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action

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