Bastani Mahta, Raoufy Mohammad Reza, Khakpour-Taleghani Behrooz, Rostampour Mohammad, Jafari Adele, Rohampour Kambiz
Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Brain Res. 2025 Aug 26:149902. doi: 10.1016/j.brainres.2025.149902.
Treatment-resistant depression (TRD), marked by persistent depressive symptoms unresponsive to standard treatments, presents a significant challenge in psychiatry. Deep brain stimulation (DBS) has emerged as a novel intervention for TRD. This study examined the impact of DBS in the olfactory bulb (OB) on depressive symptoms, local field potentials (LFPs), and the medial prefrontal cortex (mPFC)-ventral hippocampus (vHPC) connectivity. Thirty-six male Wistar rats were assigned to four groups: control, chronic mild stress (CMS), CMS + DBS, and DBS. Stereotactic surgery was performed to implant electrodes in the OB, mPFC, and vHPC. The CMS protocol was administered for 3 weeks to induce depression. Behavioral assessments included the sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). During the final 4 days of CMS induction, the DBS groups received OB stimulation for one hour daily. On day 22, LFPs were recorded from the mPFC and vHPC and analyzed using MATLAB. Data were evaluated using ANOVA, with P-values ≤ 0.05 considered significant. Results indicated that three weeks of CMS reduced low-frequency gamma power in the mPFC and overall gamma power in the vHPC, along with decreased delta and theta band coherence between these regions. CMS also increased delta, theta, and alpha band power during exploration. OB-DBS improved depressive-like behaviors, enhanced low-frequency gamma power in both mPFC and vHPC, and increased delta and theta coherence. These findings suggest that depression's pathogenesis involves alterations in the mPFC-vHPC neural network, and that OB-DBS may counteract these changes, offering a potential therapeutic target for TRD.
难治性抑郁症（TRD）以对标准治疗无反应的持续性抑郁症状为特征，是精神病学领域的一项重大挑战。深部脑刺激（DBS）已成为治疗TRD的一种新型干预手段。本研究考察了嗅球（OB）深部脑刺激对抑郁症状、局部场电位（LFP）以及内侧前额叶皮质（mPFC）-腹侧海马体（vHPC）连接性的影响。将36只雄性Wistar大鼠分为四组：对照组、慢性轻度应激（CMS）组、CMS + DBS组和DBS组。通过立体定向手术在OB、mPFC和vHPC植入电极。采用CMS方案3周以诱导抑郁。行为评估包括蔗糖偏好试验（SPT）、强迫游泳试验（FST）和旷场试验（OFT）。在CMS诱导的最后4天，DBS组每天接受1小时的OB刺激。在第22天，从mPFC和vHPC记录LFP，并使用MATLAB进行分析。数据采用方差分析进行评估，P值≤0.05被视为具有显著性。结果表明，3周的CMS降低了mPFC中的低频γ功率以及vHPC中的整体γ功率，同时降低了这些区域之间的δ和θ波段相干性。CMS还增加了探索过程中的δ、θ和α波段功率。OB-DBS改善了类似抑郁的行为，增强了mPFC和vHPC中的低频γ功率，并增加了δ和θ相干性。这些发现表明，抑郁症的发病机制涉及mPFC-vHPC神经网络的改变，而OB-DBS可能抵消这些变化，为TRD提供了一个潜在的治疗靶点。
