PMID- 30317434 OWN - NLM STAT- MEDLINE DCOM- 20190829 LR - 20210109 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 56 IP - 6 DP - 2019 Jun TI - Medial Forebrain Bundle Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Importance of BDNF and Inflammatory Cytokines. PG - 4364-4380 LID - 10.1007/s12035-018-1381-5 [doi] AB - 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-1alpha, IL-4, IL-10, IL-12, IL-13, and IL-17 in the neuroanatomical framework of the hippocampus and NAc, increased levels of IL-1beta, IL-2, IL-5, IL-6, IL-7, IL-18, TNF-alpha, and INF-gamma 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. FAU - Dandekar, Manoj P AU - Dandekar MP AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Saxena, Ashwini AU - Saxena A AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Scaini, Giselli AU - Scaini G AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Shin, Joo Hyun AU - Shin JH AD - Department of Neurosurgery, McGovern Medical School, Mischer Neurosurgical Associates, The University of Texas Health Science Center at Houston (UTHealth), 6400 Fannin, Suite 2800, Houston, TX, 77030, USA. FAU - Migut, Agata AU - Migut A AD - Department of Neurosurgery, McGovern Medical School, Mischer Neurosurgical Associates, The University of Texas Health Science Center at Houston (UTHealth), 6400 Fannin, Suite 2800, Houston, TX, 77030, USA. FAU - Giridharan, Vijayasree Vayalanellore AU - Giridharan VV AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Zhou, Yuzhi AU - Zhou Y AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. AD - Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, People's Republic of China. FAU - Barichello, Tatiana AU - Barichello T AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. AD - Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Soares, Jair C AU - Soares JC AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. AD - Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Quevedo, Joao AU - Quevedo J AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. AD - Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. AD - Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. FAU - Fenoy, Albert J AU - Fenoy AJ AUID- ORCID: 0000-0002-9554-9885 AD - Department of Neurosurgery, McGovern Medical School, Mischer Neurosurgical Associates, The University of Texas Health Science Center at Houston (UTHealth), 6400 Fannin, Suite 2800, Houston, TX, 77030, USA. Albert.J.Fenoy@uth.tmc.edu. LA - eng PT - Journal Article DEP - 20181013 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Adrenocorticotropic Hormone/blood/cerebrospinal fluid MH - *Anhedonia MH - Animals MH - *Behavior, Animal MH - Brain-Derived Neurotrophic Factor/blood/cerebrospinal fluid/*metabolism MH - C-Reactive Protein/cerebrospinal fluid/metabolism MH - Cytokines/*metabolism MH - *Deep Brain Stimulation MH - Depression/blood/cerebrospinal fluid/*complications/physiopathology MH - Disease Models, Animal MH - Feeding Behavior MH - Hippocampus/metabolism MH - Inflammation Mediators/*metabolism MH - Male MH - Medial Forebrain Bundle/*pathology MH - Motor Activity MH - Nucleus Accumbens/metabolism MH - Rats, Wistar MH - Stress, Psychological/blood/cerebrospinal fluid/complications/physiopathology OTO - NOTNLM OT - Anhedonia OT - BDNF OT - Chronic unpredictable mild stress OT - Cytokines OT - Deep brain stimulation OT - MFB EDAT- 2018/10/15 06:00 MHDA- 2019/08/30 06:00 CRDT- 2018/10/15 06:00 PHST- 2018/05/08 00:00 [received] PHST- 2018/10/04 00:00 [accepted] PHST- 2018/10/15 06:00 [pubmed] PHST- 2019/08/30 06:00 [medline] PHST- 2018/10/15 06:00 [entrez] AID - 10.1007/s12035-018-1381-5 [pii] AID - 10.1007/s12035-018-1381-5 [doi] PST - ppublish SO - Mol Neurobiol. 2019 Jun;56(6):4364-4380. doi: 10.1007/s12035-018-1381-5. Epub 2018 Oct 13.