Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Neuroscience. 2023 Aug 1;524:21-36. doi: 10.1016/j.neuroscience.2023.05.034. Epub 2023 Jun 5.
Allergic asthma is a common chronic inflammatory condition associated with psychiatric comorbidities. Notably depression, correlated with adverse outcomes in asthmatic patients. Peripheral inflammation's role in depression has been shown previously. However, evidence regarding the effects of allergic asthma on the medial prefrontal cortex (mPFC)-ventral hippocampus (vHipp) interactions, an important neurocircuitry in affective regulation, is yet to be demonstrated. Herein, we investigated the effects of allergen exposure in sensitized rats on the immunoreactivity of glial cells, depression-like behavior, brain regions volume, as well as activity and connectivity of the mPFC-vHipp circuit. We found that allergen-induced depressive-like behavior was associated with more activated microglia and astrocytes in mPFC and vHipp, as well as reduced hippocampus volume. Intriguingly, depressive-like behavior was negatively correlated with mPFC and hippocampus volumes in the allergen-exposed group. Moreover, mPFC and vHipp activity were altered in asthmatic animals. Allergen disrupted the strength and direction of functional connectivity in the mPFC-vHipp circuit so that, unlike normal conditions, mPFC causes and modulates vHipp activity. Our results provide new insight into the underlying mechanism of allergic inflammation-induced psychiatric disorders, aiming to develop new interventions and therapeutic approaches for improving asthma complications.
过敏性哮喘是一种常见的慢性炎症性疾病，与精神共病有关。特别是抑郁症与哮喘患者的不良预后相关。先前已经证明了外周炎症在抑郁症中的作用。然而，关于过敏性哮喘对内侧前额叶皮层（mPFC）-腹侧海马（vHipp）相互作用的影响的证据尚未得到证实，这是情感调节的一个重要神经回路。在此，我们研究了致敏大鼠暴露于过敏原对神经胶质细胞免疫反应性、抑郁样行为、脑区体积以及 mPFC-vHipp 回路的活动和连接性的影响。我们发现，过敏原诱导的抑郁样行为与 mPFC 和 vHipp 中更活跃的小胶质细胞和星形胶质细胞有关，同时海马体积减小。有趣的是，在暴露于过敏原的组中，抑郁样行为与 mPFC 和海马体体积呈负相关。此外，哮喘动物的 mPFC 和 vHipp 活动发生改变。过敏原破坏了 mPFC-vHipp 回路的功能连接的强度和方向，以至于与正常情况不同，mPFC 引起并调节 vHipp 活动。我们的结果为过敏性炎症引起的精神障碍的潜在机制提供了新的见解，旨在为改善哮喘并发症开发新的干预和治疗方法。
