Rani Barbara, Santangelo Andrea, Romano Adele, Koczwara Justyna Barbara, Friuli Marzia, Provensi Gustavo, Blandina Patrizio, Casarrubea Maurizio, Gaetani Silvana, Passani Maria Beatrice, Costa Alessia
Dipartimento di Scienze della Salute, Università di Firenze (I), Italy.
Dipartimento di Fisiologia e Farmacologia 'V. Erspamer', Sapienza Università di Roma, Roma, Italy.
Neurobiol Stress. 2021 Mar 17;14:100317. doi: 10.1016/j.ynstr.2021.100317. eCollection 2021 May.
The physiological mechanisms underlying the complex interplay between life stressors and metabolic factors is receiving growing interest and is being analyzed as one of the many factors contributing to depressive illness. The brain histaminergic system modulates neuronal activity extensively and we demonstrated that its integrity is necessary for peripheral signals such as the bioactive lipid mediator oleoylethanolamide (OEA) to exert its central actions. Here, we investigated the role of brain histamine and its interaction with OEA in response to chronic social defeat stress (CSDS), a preclinical protocol widely used to study physio-pathological mechanisms underlying symptoms observed in depression. Both histidine decarboxylase null (HDC) and HDC mice were subjected to CSDS for 21 days and treated with either OEA or vehicle daily, starting 10 days after CSDS initiation, until sacrifice. Undisturbed mice served as controls. To test the hypothesis of a histamine-OEA interplay on behavioral responses affected by chronic stress, tests encompassing the social, ethological and memory domains were used. CSDS caused cognitive and social behavior impairments in both genotypes, however, only stressed HDC mice responded to the beneficial effects of OEA. To detect subtle behavioral features, an advanced multivariate approach known as T-pattern analysis was used. It revealed unexpected differences of the organization of behavioral sequences during mice social interaction between the two genotypes. These data confirm the centrality of the neurotransmitter histamine as a modulator of complex behavioral responses and directly implicate OEA as a protective agent against social stress consequences in a histamine dependent fashion.
生活应激源与代谢因素之间复杂相互作用的生理机制正受到越来越多的关注，并被作为导致抑郁症的众多因素之一进行分析。脑组胺能系统广泛调节神经元活动，我们证明其完整性对于生物活性脂质介质油酰乙醇胺（OEA）等外周信号发挥其中心作用是必要的。在此，我们研究了脑组胺的作用及其与OEA在应对慢性社会挫败应激（CSDS）中的相互作用，CSDS是一种广泛用于研究抑郁症中观察到的症状背后生理病理机制的临床前方案。组氨酸脱羧酶基因敲除（HDC）小鼠和野生型小鼠均接受21天的CSDS，并从CSDS开始10天后每天用OEA或赋形剂处理，直至处死。未受干扰的小鼠作为对照。为了检验组胺 - OEA相互作用对受慢性应激影响的行为反应的假设，使用了涵盖社交、行为学和记忆领域的测试。CSDS在两种基因型小鼠中均导致认知和社交行为受损，然而，只有应激的HDC小鼠对OEA的有益作用有反应。为了检测细微的行为特征，使用了一种称为T型模式分析的先进多变量方法。它揭示了两种基因型小鼠在社交互动过程中行为序列组织的意外差异。这些数据证实了神经递质组胺作为复杂行为反应调节剂的核心地位，并直接表明OEA以组胺依赖的方式作为对抗社会应激后果的保护剂。
