Journal
MOLECULAR NEUROBIOLOGY
Volume 56, Issue 6, Pages 4364-4380Publisher
SPRINGER
DOI: 10.1007/s12035-018-1381-5
Keywords
Deep brain stimulation; MFB; Anhedonia; Chronic unpredictable mild stress; BDNF; Cytokines
Categories
Funding
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth)
- FAPESC
- Instituto Cerebro e Mente
- UNESC
- Dunn Foundation
- Pat Rutherford, Jr. Chair in Psychiatry at UTHealth
- Mischer Neurological Institute
- CNPq
- [R01MH068766]
- [K24 RR020571]
Ask authors/readers for more resources
Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) displays a promising antidepressant effects in patients with treatment-refractory depression; however, a clear consensus on underlying mechanisms is still enigmatic. Herein, we investigated the effects of MFB-DBS on anhedonic-like behavior using the Froot Loops (R) consumption in a chronic unpredictable mild stress (CUS) model of depression, biochemical estimation of peripheral and central inflammatory cytokines, stress hormone, and brain-derived neurotrophic factor (BDNF). Seven days of MFB-DBS significantly reversed the 42-day CUS-generated anhedonic-like phenotype (p<0.02) indicated by an increase in Froot Loops (R) consumption. Gross locomotor activity and body weight remained unaffected across the different groups. A dramatic augmentation of adrenocorticotropic hormone levels was seen in the plasma and cerebrospinal fluid (CSF) samples of CUS rats, which significantly reduced following MFB-DBS treatment. However, C-reactive protein levels were found to be unaffected. Interestingly, decreased levels of BDNF in the CUS animals were augmented in the plasma, CSF, and hippocampus following MFB-DBS, but remained unaltered in the nucleus accumbens (NAc). While multiplex assay revealed no change in the neuronal levels of inflammatory cytokines including IL-1, IL-4, IL-10, IL-12, IL-13, and IL-17 in the neuroanatomical framework of the hippocampus and NAc, increased levels of IL-1, IL-2, IL-5, IL-6, IL-7, IL-18, TNF-, and INF- were seen in these brain structures after CUS and were differentially modulated in the presence of MFB stimulation. Here, we show that there is dysregulation of BDNF and neuroimmune mediators in a stress-driven chronic depression model, and that chronic MFB-DBS has the potential to undo these aberrations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available