Intranasal immune challenge, brain cytokines and gender differences in depression

鼻内免疫挑战、脑细胞因子和抑郁症的性别差异

基本信息

批准号：
7267958
负责人：
Leonardo H Tonelli
金额：
$ 16.22万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7267958
关键词：
Affect Age Air Animal Model Animals Anti-Inflammatory Agents Anxiety Bacteria Behavior Behavioral Behavioral Mechanisms Biological Brain Clinical Research Condition Data Depression and Suicide Development Dexamethasone Disease Economic Conditions Environment Environmental Risk Factor Epidemiologic Studies Estradiol Estrogens Evaluation Exploratory/Developmental Grant Female Future Gender Gene Expression Genes Goals Gonadal Hormones Gonadal structure Health Health Priorities Hormonal Hormones Human Immune Immune response Immune system Incidence Individual Inflammation Inflammatory Inflammatory Response Inherited Intranasal Administration Knowledge Lead Link Lipopolysaccharides Literature Mental Depression Mental disorders Molecular Mood Disorders Moods Motor Activity Nasal cavity Outcome Peripheral Photoperiod Population Prevention Process Productivity Psychiatrist Public Health Quality of life Range Rattus Relative (related person)Reporting Research Research Personnel Respiratory Tract Infections Reverse Transcriptase Polymerase Chain Reaction Rodent Route Sex Characteristics Suicide Swimming Techniques Testing Time Upper respiratory tract Viral Virus Virus Diseases Woman Work accomplished suicide base brain tissue cytokine depressive symptoms innovation intraperitoneal mRNA Expression male member men novel novel strategies pathogen prevent programs research study response sex viral DNA

项目摘要

DESCRIPTION (provided by applicant): Epidemiological studies report that women are more likely than men to be affected by depression and that depression occurs more frequently in early spring. The biological reasons for these increased incidences are highly debated. Because many inflammatory conditions such as certain bacterial and viral respiratory infections peak around the same period of time, we hypothesize that peripheral inflammation will induce cytokine expression in the brain, that this cytokine expression will induce depression and that this effect will be higher in females. This R21 application is part of a broader goal of developing an animal model of neuroimmune interactions to study the mechanisms that may be promoting the higher incidence of depression and anxiety in women and during early spring. The objective of the proposed studies is to determine in a rodent animal model the relationship between peripheral activation of the immune response, expression of inflammatory genes in the brain and the effects of gonadal hormones in the modulation of behavioral responses of depression and anxiety. Based on our preliminary studies, we hypothesize that first: peripheral activation of the immune response due to inflammation in the upper-respiratory tract will induce cytokine expression in the brain, second: that this cytokine expression will be more pronounced in females as compared to males due to the presence of gonadal hormones, and third that this cytokine expression will affect the behavior of rats as demonstrated by increasing immobility time in the forced swim test. Treated animals with gonadal hormones and untreated animals will be challenged with bacterial and viral products in the nasal cavities and their cytokine profile in the brain will be determined by real-time RT-PCR. Another group of animals under the same conditions will be evaluated in the forced swim test and open field activity and their cytokine expression in the brain will be also determined. Administration of intranasal anti-inflammatory agents after the immune challenge will be used to test if they prevent cytokine expression in the brain and behavioral responses of depression. The results of the experiments proposed in this R21 application are expected to provide important preliminary data about gender differences and regulatory effects of gonadal hormones on inflammatory gene expression in the brain after intranasal immune-challenge. In addition, it will provide information about the interaction between gonadal hormones and cytokines in the modulation of behavioral responses to depression and anxiety. This information is not currently available in the literature and is critical to the initiation of studies on the mechanisms by which environmental factors in coordination with hormonal status may affect mood disorders. This information may be useful to prevent and treat depression in women.

描述（由申请人提供）：流行病学研究报告称，女性比男性更容易受到抑郁症的影响，并且抑郁症在早春发生的频率更高。这些发病率增加的生物学原因备受争议。由于许多炎症状况（例如某些细菌和病毒呼吸道感染）大约在同一时间段达到高峰，因此我们假设周围炎症会诱导大脑中细胞因子的表达，这种细胞因子的表达会诱发抑郁症，并且这种效应在女性中会更高。 R21 的应用是开发神经免疫相互作用动物模型的更广泛目标的一部分，以研究可能促进女性和早春抑郁和焦虑发病率较高的机制。拟议研究的目的是在啮齿动物模型中确定免疫反应的外周激活、大脑中炎症基因的表达以及性腺激素在调节抑郁和焦虑行为反应中的作用之间的关系。根据我们的初步研究，我们假设：第一：上呼吸道炎症引起的外周免疫反应激活将诱导大脑中细胞因子的表达；第二：与男性相比，女性中这种细胞因子的表达更为明显由于性腺激素的存在，第三，这种细胞因子的表达会影响大鼠的行为，如强迫游泳测试中增加的不动时间所证明的。用性腺激素治疗的动物和未治疗的动物将受到鼻腔中细菌和病毒产物的攻击，并且它们在大脑中的细胞因子谱将通过实时 RT-PCR 测定。另一组在相同条件下的动物将在强迫游泳测试和旷场活动中进行评估，并且还将测定它们在大脑中的细胞因子表达。免疫攻击后鼻内施用抗炎药将用于测试它们是否可以防止大脑中细胞因子的表达和抑郁症的行为反应。 R21申请中提出的实验结果预计将提供有关性别差异和性腺激素对鼻内免疫攻击后大脑炎症基因表达的调节作用的重要初步数据。此外，它将提供有关性腺激素和细胞因子在调节抑郁和焦虑行为反应中相互作用的信息。该信息目前在文献中尚未获得，对于启动环境因素与激素状态协调可能影响情绪障碍的机制的研究至关重要。这些信息可能有助于预防和治疗女性抑郁症。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Acute Stress Promotes Aggressive-Like Behavior in Rats Made Allergic to Tree Pollen.

急性压力会促进对树花粉过敏的老鼠出现攻击性行为。

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
Tonelli, Leonardo H;Hoshino, Akina;Katz, Morgan;Postolache, Teodor T
通讯作者：
Postolache, Teodor T

Expression and regulation in the brain of the chemokine CCL27 gene locus.

趋化因子 CCL27 基因位点在大脑中的表达和调节。

DOI：
发表时间：
2010-08-25
期刊：
影响因子：
3.3
作者：
Gunsolly, Chad;Nicholson, James D;Listwak, Samuel J;Ledee, Dolena;Zelenka, Peggy;Verthelyi, Daniela;Chapoval, Svetlana;Keegan, Achsah;Tonelli, Leonardo H
通讯作者：
Tonelli, Leonardo H

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.

自杀受害者的眶额皮质细胞因子表达升高。

DOI：
发表时间：
2008-03
期刊：
影响因子：
6.7
作者：
Tonelli, L H;Stiller, J;Rujescu, D;Giegling, I;Schneider, B;Maurer, K;Schnabel, A;Möller, H;Chen, H H;Postolache, T T
通讯作者：
Postolache, T T

Allergy: a risk factor for suicide?

过敏：自杀的危险因素？

DOI：
发表时间：
2008-09
期刊：
影响因子：
0
作者：
Postolache, Teodor T;Komarow, Hirsh;Tonelli, Leonardo H
通讯作者：
Tonelli, Leonardo H

Allergic rhinitis induces anxiety-like behavior and altered social interaction in rodents.

过敏性鼻炎会引起啮齿类动物的焦虑样行为并改变社交互动。

DOI：
发表时间：
2009-08
期刊：
影响因子：
0
作者：
Tonelli, Leonardo H;Katz, Morgan;Kovacsics, Colleen E;Gould, Todd D;Joppy, Belzora;Hoshino, Akina;Hoffman, Gloria;Komarow, Hirsh;Postolache, Teodor T
通讯作者：
Postolache, Teodor T