TY - JOUR
T1 - Neuroinflammation and aberrant hippocampal plasticity in a mouse model of emotional stress evoked by exposure to ultrasound of alternating frequencies
AU - Pavlov, Dmitrii
AU - Bettendorff, Lucien
AU - Gorlova, Anna
AU - Olkhovik, Andrey
AU - Kalueff, Allan
AU - Ponomarev, Eugene D.
AU - Inozemtsev, Anatoly
AU - Chekhonin, Vladimir
AU - Lesch, Klaus-Peter
AU - Anthony, Daniel C.
AU - Strekalova, Tatyana
N1 - Funding Information:
This work was supported by Erasmus foundation (E+2016-KA107-SM to DP and LB), Helix Laboratory Services (to AO) the European Union’s Seventh Framework Programme under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), Research Grant Council-General Research Fund grant, reference no. 14113316 (Hong Kong Government, Hong Kong), a Research Grant Council - Areas of Excellence Fund grant (Hong Kong Government, Hong Kong), reference no. AoE/M-604/16 (to EDP) and “5–100” Russian Research Excellence program (to TS and KPL). The funding bodies had no influence on the study design, the collection, analysis and the interpretation of data, the writing of the report and in the decision to submit the article for publication. LB is Research Director of the F.R.S.-FNRS (Belgium). We would like to acknowledge valuable contribution of Dr. Elizaveta Muravieva (Rochester University, USA) and Arina Kazakova (Mount Holyoke College, USA) in this paper.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/3/2
Y1 - 2019/3/2
N2 - Emotional stress is a form of stress evoked by processing negative mental experience rather than an organic or physical disturbance and is a frequent cause of neuropsychiatric pathologies, including depression. Susceptibility to emotional stress is commonly regarded as a human-specific trait that is challenging to model in other species. Recently, we showed that a 3-week-long exposure to ultrasound of unpredictable alternating frequencies within the ranges of 20-25 kHz and 25-45 kHz can induce depression-like characteristics in laboratory mice and rats. In an anti-depressant sensitive manner, exposure decreases sucrose preference, elevates behavioural despair, increases aggression, and alters serotonin-related gene expression. To further investigate this paradigm, we studied depression/distress-associated markers of neuroinflammation, neuroplasticity, oxidative stress and the activity of glycogen synthase kinase-3 (GSK-3) isoforms in the hippocampus of male mice. Stressed mice exhibited a decreased density of Ki67-positive and DCX-positive cells in the subgranular zone of hippocampus, and altered expression of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and anti-apoptotic protein kinase B phosphorylated at serine 473 (AktpSer473). The mice also exhibited increased densities of Iba-1-positive cells, increased oxidative stress, increased levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) in the hippocampus and plasma, and elevated activity of GSK-3 isoforms. Together, the results of our investigation have revealed that unpredictable alternating ultrasound evokes behavioural and molecular changes that are characteristic of the depressive syndrome and validates this new and simple method of modeling emotional stress in rodents.
AB - Emotional stress is a form of stress evoked by processing negative mental experience rather than an organic or physical disturbance and is a frequent cause of neuropsychiatric pathologies, including depression. Susceptibility to emotional stress is commonly regarded as a human-specific trait that is challenging to model in other species. Recently, we showed that a 3-week-long exposure to ultrasound of unpredictable alternating frequencies within the ranges of 20-25 kHz and 25-45 kHz can induce depression-like characteristics in laboratory mice and rats. In an anti-depressant sensitive manner, exposure decreases sucrose preference, elevates behavioural despair, increases aggression, and alters serotonin-related gene expression. To further investigate this paradigm, we studied depression/distress-associated markers of neuroinflammation, neuroplasticity, oxidative stress and the activity of glycogen synthase kinase-3 (GSK-3) isoforms in the hippocampus of male mice. Stressed mice exhibited a decreased density of Ki67-positive and DCX-positive cells in the subgranular zone of hippocampus, and altered expression of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and anti-apoptotic protein kinase B phosphorylated at serine 473 (AktpSer473). The mice also exhibited increased densities of Iba-1-positive cells, increased oxidative stress, increased levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) in the hippocampus and plasma, and elevated activity of GSK-3 isoforms. Together, the results of our investigation have revealed that unpredictable alternating ultrasound evokes behavioural and molecular changes that are characteristic of the depressive syndrome and validates this new and simple method of modeling emotional stress in rodents.
KW - Depression
KW - Ultrasound radiation
KW - Plasticity
KW - Neuroinflammation
KW - Glycogen synthase kinase 3 (GSK-3)
KW - Mice
KW - GLYCOGEN-SYNTHASE KINASE-3
KW - MICROGLIAL ACTIVATION
KW - NEUROTROPHIC FACTORS
KW - DEPRESSION RESEARCH
KW - PREFRONTAL CORTEX
KW - ANIMAL-MODELS
KW - SOCIAL STRESS
KW - BRAIN
KW - MICE
KW - NEUROGENESIS
U2 - 10.1016/j.pnpbp.2018.11.014
DO - 10.1016/j.pnpbp.2018.11.014
M3 - Article
SN - 0278-5846
VL - 90
SP - 104
EP - 116
JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry
ER -