title: Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.
abstract: Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents.
authors.affiliation: Graduate Studies Program in Neurosciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: mileborsoi@gmail.com.
authors.forename: Milene
authors.initials: M
authors.lastname: Borsoi
authors.affiliation: Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Camila Boque
authors.initials: CB
authors.lastname: Antonio
authors.affiliation: Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Liz Girardi
authors.initials: LG
authors.lastname: Müller
authors.affiliation: Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Alice Fialho
authors.initials: AF
authors.lastname: Viana
authors.affiliation: Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Vivian
authors.initials: V
authors.lastname: Hertzfeldt
authors.affiliation: Graduate Studies Program in Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Paula Santana
authors.initials: PS
authors.lastname: Lunardi
authors.affiliation: Graduate Studies Program in Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zanotto
authors.affiliation: Graduate Studies Program in Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nardin
authors.affiliation: College of Veterinary Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ravazzolo
authors.affiliation: Graduate Studies Program in Neurosciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Studies Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Stela Maris Kuze
authors.initials: SM
authors.lastname: Rates
authors.affiliation: Graduate Studies Program in Neurosciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Studies Program in Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000503:physiopathology; D018698:Glutamic Acid / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D019964:Mood Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013312:Stress, Physiological; D013550:Swimming
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002147:Calmodulin; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005978:Glutathione
keywords: Repeated forced swimming; brain-derived neurotrophic factor; frontal cortex; glutamate uptake; hippocampus; prepulse inhibition