Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice

Roberto Coccurello, Adam Bielawski, Agnieszka Zelek-Molik, Jerzy Vetulani, Marta Kowalska, Francesca R. D'Amato, Irena Nalepa

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli. We found that repeated exposure to CB experience produced anhedonic-like behavior in terms of reduced saccharin intake and α1-adrenoceptor downregulation in piriform and somatosensory cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a selective decrease of α1B-adrenoceptor binding sites in the cingulate cortex and hippocampus and an increase of hippocampal α1A and α1B receptor, but not of α1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family proteins was found at the hippocampal level. Together, these data provide evidence that the early exposure to CB experience produced enduring downregulation of α1-adrenoceptors in the prefrontal-limbic forebrain/limbic midbrain network, which plays a key role in the processing of olfactory information and reaction to rewarding stimuli. Finally, these data show that CB experience can "prime" the hippocampal circuitry and promote the expression of antiapoptotic factors that can confer potential neuroprotection to subsequent adversity.

Original languageEnglish
Pages (from-to)161-169
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume48
DOIs
Publication statusPublished - Jan 3 2014

Fingerprint

Adrenergic Receptors
Mothers
Brain
Heat-Shock Proteins
Automatic Data Processing
Hippocampus
Down-Regulation
Binding Sites
Saccharin
Thalamic Nuclei
Messenger RNA
Somatosensory Cortex
Gyrus Cinguli
Prosencephalon
Mesencephalon
Amygdala
Prefrontal Cortex
Mood Disorders
Psychiatry
Proteins

Keywords

  • α-Adrenoceptors
  • Anhedonia
  • Bcl-2 proteins
  • Early life adversity
  • Heat shock proteins
  • Olfactory learning

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

Cite this

Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice. / Coccurello, Roberto; Bielawski, Adam; Zelek-Molik, Agnieszka; Vetulani, Jerzy; Kowalska, Marta; D'Amato, Francesca R.; Nalepa, Irena.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 48, 03.01.2014, p. 161-169.

Research output: Contribution to journalArticle

Coccurello, Roberto ; Bielawski, Adam ; Zelek-Molik, Agnieszka ; Vetulani, Jerzy ; Kowalska, Marta ; D'Amato, Francesca R. ; Nalepa, Irena. / Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014 ; Vol. 48. pp. 161-169.
@article{f452ac9ec71f4ba3a149eb3a328bd5e4,
title = "Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice",
abstract = "Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli. We found that repeated exposure to CB experience produced anhedonic-like behavior in terms of reduced saccharin intake and α1-adrenoceptor downregulation in piriform and somatosensory cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a selective decrease of α1B-adrenoceptor binding sites in the cingulate cortex and hippocampus and an increase of hippocampal α1A and α1B receptor, but not of α1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family proteins was found at the hippocampal level. Together, these data provide evidence that the early exposure to CB experience produced enduring downregulation of α1-adrenoceptors in the prefrontal-limbic forebrain/limbic midbrain network, which plays a key role in the processing of olfactory information and reaction to rewarding stimuli. Finally, these data show that CB experience can {"}prime{"} the hippocampal circuitry and promote the expression of antiapoptotic factors that can confer potential neuroprotection to subsequent adversity.",
keywords = "α-Adrenoceptors, Anhedonia, Bcl-2 proteins, Early life adversity, Heat shock proteins, Olfactory learning",
author = "Roberto Coccurello and Adam Bielawski and Agnieszka Zelek-Molik and Jerzy Vetulani and Marta Kowalska and D'Amato, {Francesca R.} and Irena Nalepa",
year = "2014",
month = "1",
day = "3",
doi = "10.1016/j.pnpbp.2013.10.004",
language = "English",
volume = "48",
pages = "161--169",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice

AU - Coccurello, Roberto

AU - Bielawski, Adam

AU - Zelek-Molik, Agnieszka

AU - Vetulani, Jerzy

AU - Kowalska, Marta

AU - D'Amato, Francesca R.

AU - Nalepa, Irena

PY - 2014/1/3

Y1 - 2014/1/3

N2 - Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli. We found that repeated exposure to CB experience produced anhedonic-like behavior in terms of reduced saccharin intake and α1-adrenoceptor downregulation in piriform and somatosensory cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a selective decrease of α1B-adrenoceptor binding sites in the cingulate cortex and hippocampus and an increase of hippocampal α1A and α1B receptor, but not of α1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family proteins was found at the hippocampal level. Together, these data provide evidence that the early exposure to CB experience produced enduring downregulation of α1-adrenoceptors in the prefrontal-limbic forebrain/limbic midbrain network, which plays a key role in the processing of olfactory information and reaction to rewarding stimuli. Finally, these data show that CB experience can "prime" the hippocampal circuitry and promote the expression of antiapoptotic factors that can confer potential neuroprotection to subsequent adversity.

AB - Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli. We found that repeated exposure to CB experience produced anhedonic-like behavior in terms of reduced saccharin intake and α1-adrenoceptor downregulation in piriform and somatosensory cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a selective decrease of α1B-adrenoceptor binding sites in the cingulate cortex and hippocampus and an increase of hippocampal α1A and α1B receptor, but not of α1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family proteins was found at the hippocampal level. Together, these data provide evidence that the early exposure to CB experience produced enduring downregulation of α1-adrenoceptors in the prefrontal-limbic forebrain/limbic midbrain network, which plays a key role in the processing of olfactory information and reaction to rewarding stimuli. Finally, these data show that CB experience can "prime" the hippocampal circuitry and promote the expression of antiapoptotic factors that can confer potential neuroprotection to subsequent adversity.

KW - α-Adrenoceptors

KW - Anhedonia

KW - Bcl-2 proteins

KW - Early life adversity

KW - Heat shock proteins

KW - Olfactory learning

UR - http://www.scopus.com/inward/record.url?scp=84886674068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886674068&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2013.10.004

DO - 10.1016/j.pnpbp.2013.10.004

M3 - Article

C2 - 24128685

AN - SCOPUS:84886674068

VL - 48

SP - 161

EP - 169

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

ER -