title: Cognitive impairment induced by permanent bilateral common carotid occlusion exacerbates depression-related behavioral, biochemical, immunological and neuronal markers.
abstract: There is a strong link between cognitive impairment and depression, but up to date it is not clear whether cognitive impairment is 'cause' or 'consequence' of depression. Therefore, we here examined the effect of cognitive impairment induced by permanent occlusion of common carotid arteries, a model known as two-vessel occlusion (2VO), on chronic unpredictable stress (CUS)-induced depression-related markers in rats. Male Sprague-Dawley rats underwent 2VO or sham surgery. Sixty days after the surgery, the cognitive function of the rats was tested using the radial arm maze task measuring working and reference memory. Subsequently, the animals were randomly assigned to undergo 21 days of CUS or to stay non-stressed. One week after the last stressor, psychomotor retardation, a feature of depression-like behavior, was assessed using the forced swim test (FST) by measuring time spent on immobility. Plasma amino acid (glutamine, glutamate and glycine) and serum pro-inflammatory cytokine (interleukin 6) levels, and hippocampus CA1 neuronal damage were measured 24h after FST exposure. Results show that 2VO increased immobility in the FST only when rats had been exposed to CUS. In addition, 2VO surgery intensified the effect of CUS on IL-6, glutamate and glycine levels and increased CA1 hippocampal damage. In conclusion, our findings show that cognitive impairment may predispose to depression by intensifying the effect of stress on depression-related behavioral, biochemical, immunological and neuronal markers.
authors.affiliation: Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Khojasteh
authors.affiliation: Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: arezoonahavandi1999@gmail.com.
authors.forename: Arezo
authors.initials: A
authors.lastname: Nahavandi
authors.affiliation: Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Mehrpouya
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: Razi Drug Research Center, and Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Mirzamohammadi
authors.affiliation: Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Neurophysiology Research Center, Hamedan University of Medical Sciences, Hamedan, Iran.
authors.forename: Safoora
authors.initials: S
authors.lastname: Raufi
authors.affiliation: Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Barati
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002340:Carotid Artery Diseases / Q000150:complications*; D002851:Chromatography, High Pressure Liquid; D003072:Cognition Disorders / Q000097:blood / Q000150:complications* / Q000209:etiology*; D003463:Cues; D003863:Depression / Q000209:etiology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D018698:Glutamic Acid; D005998:Glycine
keywords: Cognitive impairment; Depression; Glutamate; Glycine; Interleukin 6; Stress; Two-vessel occlusion