open access publication

Article, 2022

Neuroglobin deficiency increases seizure susceptibility but does not affect basal behavior in mice

Journal of Neuroscience Research, ISSN 0360-4012, 1097-4547, Volume 100, 10, Pages 1921-1932, 10.1002/jnr.25105

Contributors

Gøtzsche, Casper René 0000-0003-3063-2853 [1] Woldbye, David Paul Drucker 0000-0002-6321-3850 [1] Hundahl, Christian Ansgar [2] Hay-Schmidt, Anders (Corresponding author) [1]

Affiliations

  1. [1] University of Copenhagen
    2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Novo Nordisk (Denmark)
    3. [NORA names: Novo Nordisk; Private Research; Denmark; Europe, EU; Nordic; OECD]

Abstract

Neuroglobin (Ngb) is found in the neurones of several different brain areas and is known to bind oxygen and other gaseous molecules and reactive oxygen species (ROS) in vitro, but it does not seem to act as a respiratory molecule for neurones. Using male and female Ngb-knockout (KO) mice, we addressed the role of Ngb in neuronal brain activity using behavioral tests but found no differences in general behaviors, memory processes, and anxiety-/depression-like behaviors. Oxidative stress and ROS play key roles in epileptogenesis, and oxidative injury produced by an excessive production of free radicals is involved in the initiation and progression of epilepsy. The ROS binding properties led us to hypothesize that lack of Ngb could affect central coping with excitatory stimuli. We consequently explored whether exposure to the excitatory molecule kainate (KA) would increase severity of seizures in mice lacking Ngb. We found that the duration and severity of seizures were increased, while the latency time to develop seizures was shortened in Ngb-KO compared to wildtype adult female mice. Consistently, c-fos expression after KA was significantly increased in Ngb-KO mice in the amygdala and piriform cortex, regions rich in Ngb and known to be centrally involved in seizure generation. Moreover, the measured c-fos expression levels were correlated with seizure susceptibility. With these new findings combined with previous studies we propose that Ngb could constitute an intrinsic defense mechanism against neuronal hyperexcitability and oxidative stress by buffering of ROS in amygdala and other Ngb-containing brain regions.

Keywords

Ngb, activity, adult female mice, amygdala, anxiety-/depression-like behaviors, area, basal behavior, behavior, behavioral tests, bind oxygen, binding properties, brain, brain activity, brain areas, brain regions, buffer, buffering of reactive oxygen species, c-Fos expression levels, c-fos, c-fos expression, coping, cortex, defense mechanisms, duration, epilepsy, epileptogenesis, excessive production, excessive production of free radicals, excitatory stimuli, exposure, expression, expression levels, female mice, females, findings, free radicals, gaseous molecules, general behavior, generation, hyperexcitability, in vitro, increased severity of seizures, increasing severity, initiation, injury, intrinsic defense mechanisms, kainate, lack, lack of Ngb, latency, latency time, levels, male, mechanism, memory, memory processes, mice, molecules, neuroglobin, neuronal brain activity, neuronal hyperexcitability, neurons, oxidative injury, oxidative stress, oxygen, oxygen species, piriform, piriform cortex, process, production of free radicals, progression, progression of epilepsy, properties, radicals, reactive oxygen species, region, seizure generation, seizure susceptibility, seizures, severity, severity of seizures, species, stimuli, stress, study, susceptibility, test, time

Funders

  • Lundbeck Foundation
  • A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond
  • Aase og Ejnar Danielsens Fond
  • Capital Region of Denmark

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