Deep brain stimulation of ventromedial prefrontal cortex reverses depressive-like behaviors via BDNF/TrkB signaling pathway in rats. 2023

Fanglin Liu, and Shihao Huang, and Dan Guo, and Xin Li, and Ying Han
National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing 100191, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.

OBJECTIVE Deep brain stimulation (DBS) is currently under investigation as a potential therapeutic approach for managing major depressive disorder (MDD) and ventromedial prefrontal cortex (vmPFC) is recognized as a promising target region. Therefore, the present study aimed to investigate a preclinical paradigm of bilateral vmPFC DBS and examine the molecular mechanisms underlying its antidepressant-like effects using chronic unpredictable stress (CUS) model in rats. METHODS Male rats were subjected to stereotaxic surgery and deep brain stimulation paradigm in non-stressed and CUS rats respectively, and the therapeutic effect of DBS were assessed by a series of behavioral tests including sucrose preference test, open field test, elevated plus maze test, and forced swim test. The potential involvement of the BDNF/TrkB signaling pathway and its downstream effects in this process were also investigated using western blot. RESULTS We identified that a stimulation protocol consisting of 130 Hz, 200 μA, 90 μs pulses administered for 5 h per day over a period of 7 days effectively mitigated CUS-induced depressive-like and anxiety-like behaviors in rats. These therapeutic effects were associated with the enhancement of the BDNF/TrkB signaling pathway and its downstream ERK1/2 activity. CONCLUSIONS These findings provide valuable insights into the potential clinical utility of vmPFC DBS as an approach of improving the symptoms experienced by individuals with MDD. This evidence contributes to our understanding of the neurobiological basis of depression and offers promise for the development of more effective treatments.

UI MeSH Term Description Entries
D008297 Male Males
D003863 Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. Depressive Symptoms,Emotional Depression,Depression, Emotional,Depressive Symptom,Symptom, Depressive
D003865 Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5) Depression, Involutional,Major Depressive Disorder,Melancholia, Involutional,Paraphrenia, Involutional,Psychosis, Involutional,Depressive Disorders, Major,Involutional Depression,Involutional Melancholia,Involutional Paraphrenia,Involutional Paraphrenias,Involutional Psychoses,Involutional Psychosis,Major Depressive Disorders,Paraphrenias, Involutional,Psychoses, Involutional
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013315 Stress, Psychological Stress wherein emotional factors predominate. Cumulative Stress, Psychological,Emotional Stress,Individual Stressors,Life Stress,Psychological Cumulative Stress,Psychological Stress Experience,Psychological Stress Overload,Psychologically Stressful Conditions,Stress Experience, Psychological,Stress Measurement, Psychological,Stress Overload, Psychological,Stress Processes, Psychological,Stress, Emotional,Stressful Conditions, Psychological,Psychological Stress,Stress, Psychologic,Stressor, Psychological,Condition, Psychological Stressful,Condition, Psychologically Stressful,Conditions, Psychologically Stressful,Cumulative Stresses, Psychological,Experience, Psychological Stress,Individual Stressor,Life Stresses,Measurement, Psychological Stress,Overload, Psychological Stress,Psychologic Stress,Psychological Cumulative Stresses,Psychological Stress Experiences,Psychological Stress Measurement,Psychological Stress Measurements,Psychological Stress Overloads,Psychological Stress Processe,Psychological Stress Processes,Psychological Stresses,Psychological Stressful Condition,Psychological Stressful Conditions,Psychological Stressor,Psychological Stressors,Psychologically Stressful Condition,Stress Experiences, Psychological,Stress Processe, Psychological,Stress, Life,Stress, Psychological Cumulative,Stressful Condition, Psychological,Stressful Condition, Psychologically,Stressor, Individual
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017397 Prefrontal Cortex The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin. Anterior Prefrontal Cortex,Brodmann Area 10,Brodmann Area 11,Brodmann Area 12,Brodmann Area 47,Brodmann's Area 10,Brodmann's Area 11,Brodmann's Area 12,Brodmann's Area 47,Pars Orbitalis,Frontal Sulcus,Gyrus Frontalis Inferior,Gyrus Frontalis Superior,Gyrus Orbitalis,Gyrus Rectus,Inferior Frontal Gyrus,Lateral Orbitofrontal Cortex,Marginal Gyrus,Medial Frontal Gyrus,Olfactory Sulci,Orbital Area,Orbital Cortex,Orbital Gyri,Orbitofrontal Cortex,Orbitofrontal Gyri,Orbitofrontal Gyrus,Orbitofrontal Region,Rectal Gyrus,Rectus Gyrus,Straight Gyrus,Subcallosal Area,Superior Frontal Convolution,Superior Frontal Gyrus,Ventral Medial Prefrontal Cortex,Ventromedial Prefrontal Cortex,Anterior Prefrontal Cortices,Area 10, Brodmann,Area 10, Brodmann's,Area 11, Brodmann,Area 11, Brodmann's,Area 12, Brodmann,Area 12, Brodmann's,Area 47, Brodmann,Area 47, Brodmann's,Area, Orbital,Area, Subcallosal,Brodmanns Area 10,Brodmanns Area 11,Brodmanns Area 12,Brodmanns Area 47,Convolution, Superior Frontal,Convolutions, Superior Frontal,Cortex, Anterior Prefrontal,Cortex, Lateral Orbitofrontal,Cortex, Orbital,Cortex, Orbitofrontal,Cortex, Prefrontal,Cortex, Ventromedial Prefrontal,Cortices, Ventromedial Prefrontal,Frontal Convolution, Superior,Frontal Gyrus, Inferior,Frontal Gyrus, Medial,Frontal Gyrus, Superior,Frontalis Superior, Gyrus,Gyrus, Inferior Frontal,Gyrus, Marginal,Gyrus, Medial Frontal,Gyrus, Orbital,Gyrus, Orbitofrontal,Gyrus, Rectal,Gyrus, Rectus,Gyrus, Straight,Gyrus, Superior Frontal,Inferior, Gyrus Frontalis,Lateral Orbitofrontal Cortices,Olfactory Sulcus,Orbital Areas,Orbital Cortices,Orbital Gyrus,Orbitalis, Pars,Orbitofrontal Cortex, Lateral,Orbitofrontal Cortices,Orbitofrontal Cortices, Lateral,Orbitofrontal Regions,Prefrontal Cortex, Anterior,Prefrontal Cortex, Ventromedial,Prefrontal Cortices, Anterior,Region, Orbitofrontal,Subcallosal Areas,Sulcus, Frontal,Superior Frontal Convolutions,Superior, Gyrus Frontalis,Ventromedial Prefrontal Cortices
D046690 Deep Brain Stimulation Therapy for MOVEMENT DISORDERS, especially PARKINSON DISEASE, that applies electricity via stereotactic implantation of ELECTRODES in specific areas of the BRAIN such as the THALAMUS. The electrodes are attached to a neurostimulator placed subcutaneously. Brain Stimulation, Deep,Electrical Stimulation of the Brain,Brain Stimulations, Deep,Deep Brain Stimulations,Stimulation, Deep Brain,Stimulations, Deep Brain

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