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 V.

AU - Ponomarev, Eugene D.

AU - Inozemtsev, Anatoly

AU - Chekhonin, Vladimir

AU - Lesсh, Klaus Peter

AU - Anthony, Daniel C.

AU - Strekalova, Tatyana

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-1β (IL-1β), 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-1β (IL-1β), 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 - Glycogen synthase kinase 3 (GSK-3)

KW - Mice

KW - Neuroinflammation

KW - Plasticity

KW - Ultrasound radiation

KW - Oxidative Stress/physiology

KW - Inflammation/physiopathology

KW - Acoustic Stimulation/methods

KW - Interleukin-1beta/metabolism

KW - Male

KW - Glycogen Synthase Kinase 3/metabolism

KW - Receptor, trkB/metabolism

KW - Ultrasonics

KW - Brain-Derived Neurotrophic Factor/metabolism

KW - Animals

KW - Stress, Psychological/physiopathology

KW - Interleukin-6/metabolism

KW - Neuronal Plasticity/physiology

KW - Mice, Inbred BALB C

KW - Hippocampus/physiopathology

KW - Isoenzymes/metabolism

KW - Depressive Disorder/physiopathology

KW - Disease Models, Animal

KW - SOCIAL STRESS

KW - NEUROTROPHIC FACTORS

KW - ANIMAL-MODELS

KW - MICE

KW - DEPRESSION RESEARCH

KW - BRAIN

KW - MICROGLIAL ACTIVATION

KW - GLYCOGEN-SYNTHASE KINASE-3

KW - PREFRONTAL CORTEX

KW - NEUROGENESIS

UR - http://www.scopus.com/inward/record.url?scp=85057300548&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2018.11.014

DO - 10.1016/j.pnpbp.2018.11.014

M3 - Article

C2 - 30472146

AN - SCOPUS:85057300548

VL - 90

SP - 104

EP - 116

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

ER -