Dataset Information

Bumetanide attenuates sevoflurane-induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test.

ABSTRACT:

Introduction

Sevoflurane acts as a gamma-aminobutyric acid subtype A receptor agonist and can induce widespread apoptosis of immature dentate granule cells in postnatal day 21 mice. The dentate granule cells of postnatal day 21 mice undergo a developmental stage when gamma-aminobutyric acid (GABA) shifts from inducing the depolarization of neurons to causing hyperpolarization. However, it is unclear whether sevoflurane induces apoptosis of immature granule cells by facilitating the depolarization or hyperpolarization of neurons.

Methods

We utilized bumetanide, an Na⁺ -K⁺ -2Cl^- cotransporter isoform 1 (NKCC1) antagonist, to determine whether the NKCC1-mediated GABA depolarization of neurons plays a role in sevoflurane-induced neuroapoptosis. We also investigated whether sevoflurane exposure is related to long-term cognitive dysfunction in postnatal day 21 mice and explored the possible protective effects of bumetanide.

Results

Bumetanide attenuated the sevoflurane-induced apoptosis of dentate granule cells in postnatal day 21 mice. Exposure to sevoflurane at postnatal day 21 mice did not affect their motor ability or anxiety level, and it had no effect on spatial learning or memory functions. However, sevoflurane exposure at postnatal day 21 impaired the pattern separation ability in the contextual fear discrimination test; bumetanide mitigated this effect of sevoflurane as well.

Conclusion

Bumetanide attenuates sevoflurane-induced apoptosis and is a promising prospect for protecting against anesthesia-induced neurotoxicity in the developing brain.

SUBMITTER: Wei K

PROVIDER: S-EPMC9660414 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Bumetanide attenuates sevoflurane-induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test.

Wei Kai K Liu Yiheng Y Yang Xiamin X Liu Jin J Li Yuan Y Deng Meng M Wang Yingwei Y

Brain and behavior 20221002 11

<h4>Introduction</h4>Sevoflurane acts as a gamma-aminobutyric acid subtype A receptor agonist and can induce widespread apoptosis of immature dentate granule cells in postnatal day 21 mice. The dentate granule cells of postnatal day 21 mice undergo a developmental stage when gamma-aminobutyric acid (GABA) shifts from inducing the depolarization of neurons to causing hyperpolarization. However, it is unclear whether sevoflurane induces apoptosis of immature granule cells by facilitating the depol ...[more]

PMID: 36184814

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Project description:Disproportionate, maladapted, and generalized fear are essential hallmarks of posttraumatic stress disorder (PTSD), which develops upon severe trauma in a subset of exposed individuals. Among the brain areas that are processing fear memories, the hippocampal formation exerts a central role linking emotional-affective with cognitive aspects. In the hippocampus, neuronal excitability is constrained by multiple GABAergic interneurons with highly specialized functions and an extensive repertoire of co-released neuromodulators. Neuropeptide Y (NPY) is one of these co-transmitters that significantly affects hippocampal signaling, with ample evidence supporting its fundamental role in emotional, cognitive, and metabolic circuitries. Here we investigated the role of NPY in relation to GABA, both released from the same interneurons of the dorsal dentate gyrus (DG), in different aspects of fear conditioning. We demonstrated that activation of dentate GABA neurons specifically during fear recall reduced cue-related as well as trace-related freezing behavior, whereas inhibition of the same neurons had no significant effects. Interestingly, concomitant overexpression of NPY in these neurons did not further modify fear recall, neither under baseline conditions nor upon chemogenetic stimulation. However, potentially increased co-release of NPY substantially reduced contextual fear, promoted extinction learning, and long-term suppression of fear in a foreground context-conditioning paradigm. Importantly, NPY in the dorsal DG was not only expressed in somatostatin neurons, but also in parvalbumin-positive basket cells and axoaxonic cells, indicating intense feedback and feedforward modulation of hippocampal signaling and precise curtailing of neuronal engrams. Thus, these findings suggest that co-release of NPY from specific interneuron populations of the dorsal DG modifies dedicated aspects of hippocampal processing by sharpening the activation of neural engrams and the consecutive fear response. Since inappropriate and generalized fear is the major impediment in the treatment of PTSD patients, the dentate NPY system may be a suitable access point to ameliorate PTSD symptoms and improve the inherent disease course.

Dataset Information

Bumetanide attenuates sevoflurane-induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test.

Introduction

Methods

Results

Conclusion

Publications

Bumetanide attenuates sevoflurane-induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test.

Similar Datasets

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