Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats

Zsófia Varga, Dávid Csabai, A. Miseta, Ove Wiborg, Boldizsár Czéh

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40–50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
JournalBehavioural Brain Research
Volume316
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

GABAergic Neurons
Prefrontal Cortex
Neurons
Calbindins
Motor Cortex
Calbindin 2
Parvalbumins
Neuropeptide Y
Cholecystokinin
Interneurons
Somatostatin
Animal Models
Immunohistochemistry

Keywords

  • Calbindin
  • Cholecystokinin
  • Chronic mild stress
  • Mood disorder
  • Motor cortex
  • Neuropeptide Y

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats. / Varga, Zsófia; Csabai, Dávid; Miseta, A.; Wiborg, Ove; Czéh, Boldizsár.

In: Behavioural Brain Research, Vol. 316, 01.01.2017, p. 104-114.

Research output: Contribution to journalArticle

Varga, Zsófia ; Csabai, Dávid ; Miseta, A. ; Wiborg, Ove ; Czéh, Boldizsár. / Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats. In: Behavioural Brain Research. 2017 ; Vol. 316. pp. 104-114.
@article{3783399c983542a581aef3077f72ec6f,
title = "Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats",
abstract = "Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40–50{\%} in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals.",
keywords = "Calbindin, Cholecystokinin, Chronic mild stress, Mood disorder, Motor cortex, Neuropeptide Y",
author = "Zs{\'o}fia Varga and D{\'a}vid Csabai and A. Miseta and Ove Wiborg and Boldizs{\'a}r Cz{\'e}h",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.bbr.2016.08.030",
language = "English",
volume = "316",
pages = "104--114",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

TY - JOUR

T1 - Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats

AU - Varga, Zsófia

AU - Csabai, Dávid

AU - Miseta, A.

AU - Wiborg, Ove

AU - Czéh, Boldizsár

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40–50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals.

AB - Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40–50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals.

KW - Calbindin

KW - Cholecystokinin

KW - Chronic mild stress

KW - Mood disorder

KW - Motor cortex

KW - Neuropeptide Y

UR - http://www.scopus.com/inward/record.url?scp=84985947313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84985947313&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2016.08.030

DO - 10.1016/j.bbr.2016.08.030

M3 - Article

C2 - 27555539

AN - SCOPUS:84985947313

VL - 316

SP - 104

EP - 114

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -