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Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Nav) channels properties

Treccani, Giulia LU ; Yigit, Hatice ; Lingner, Thomas ; Schleuβner, Vanessa ; Mey, Franziska ; van der Kooij, Michael A. ; Wennström, Malin LU ; Herzog, David P. ; Linke, Matthias and Fricke, Markus , et al. (2021) In Neurobiology of Stress 15.
Abstract

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+... (More)

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a, could be confirmed by an increase in the density of voltage-gated sodium (Nav) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Nav channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Early life stress, Na-channels, NG2+ glia, Scn7a, Transcriptome, Translational psychiatry
in
Neurobiology of Stress
volume
15
article number
100338
publisher
Elsevier
external identifiers
  • scopus:85106222752
  • pmid:34095364
ISSN
2352-2895
DOI
10.1016/j.ynstr.2021.100338
language
English
LU publication?
yes
id
c4080105-388a-4fe4-a5ee-e0492a7d1a8c
date added to LUP
2021-12-27 14:56:53
date last changed
2024-06-15 23:22:35
@article{c4080105-388a-4fe4-a5ee-e0492a7d1a8c,
  abstract     = {{<p>The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a, could be confirmed by an increase in the density of voltage-gated sodium (Na<sub>v</sub>) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Na<sub>v</sub> channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice.</p>}},
  author       = {{Treccani, Giulia and Yigit, Hatice and Lingner, Thomas and Schleuβner, Vanessa and Mey, Franziska and van der Kooij, Michael A. and Wennström, Malin and Herzog, David P. and Linke, Matthias and Fricke, Markus and Schmeisser, Michael J. and Wegener, Gregers and Mittmann, Thomas and Trotter, Jacqueline and Müller, Marianne B.}},
  issn         = {{2352-2895}},
  keywords     = {{Early life stress; Na-channels; NG2+ glia; Scn7a; Transcriptome; Translational psychiatry}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Stress}},
  title        = {{Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Na<sub>v</sub>) channels properties}},
  url          = {{http://dx.doi.org/10.1016/j.ynstr.2021.100338}},
  doi          = {{10.1016/j.ynstr.2021.100338}},
  volume       = {{15}},
  year         = {{2021}},
}