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.
authors.affiliation: MTA - PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, 7624 Pécs, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Varga
authors.affiliation: MTA - PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, 7624 Pécs, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Csabai
authors.affiliation: Department of Laboratory Medicine, University of Pécs, Medical School, 7624 Pécs, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Miseta
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors.forename: Ove
authors.initials: O
authors.lastname: Wiborg
authors.affiliation: MTA - PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, 7624 Pécs, Hungary; Department of Laboratory Medicine, University of Pécs, Medical School, 7624 Pécs, Hungary; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark. Electronic address: czeh.boldizsar@pte.hu.
authors.forename: Boldizsár
authors.initials: B
authors.lastname: Czéh
mesh_terms: D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D002452:Cell Count; D002766:Cholecystokinin / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005518:Food Preferences / Q000502:physiology; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D009478:Neuropeptide Y; D010320:Parvalbumins; D013004:Somatostatin; D013395:Sucrose; D002766:Cholecystokinin
keywords: Calbindin; Cholecystokinin; Chronic mild stress; Mood disorder; Motor cortex; Neuropeptide Y