Delayed behavioral and genomic responses to acute combined stress in zebrafish, potentially relevant to PTSD and other stress-related disorders: Focus on neuroglia, neuroinflammation, apoptosis and epigenetic modulation

Long En Yang, Jingtao Wang, Dongmei Wang, Guojun Hu, Zi Yuan Liu, Dongni Yan, Nazar Serikuly, Erik T. Alpyshov, Konstantin A. Demin, Tatyana Strekalova, Murilo S. de Abreu, Cai Song, Allan V. Kalueff

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

Stress is a common trigger of stress-related illnesses, such as anxiety, phobias, depression and post-traumatic stress disorder (PTSD). Various animal models successfully reproduce core behaviors of these clinical conditions. Here, we develop a novel zebrafish model of stress (potentially relevant to human stress-related disorders), based on delayed persistent behavioral, endocrine and genomic responses to an acute severe ‘combined’ stressor. Specifically, one week after adult zebrafish were exposed to a complex combined 90-min stress, we assessed their behaviors in the novel tank and the light-dark box tests, as well as whole-body cortisol and brain gene expression, focusing on genomic biomarkers of microglia, astrocytes, neuroinflammation, apoptosis and epigenetic modulation. Overall, stressed fish displayed persistent anxiety-like behavior, elevated whole-body cortisol, as well as upregulated brain mRNA expression of genes encoding the glucocorticoid receptor, neurotrophin BDNF and its receptors (TrkB and P75), CD11b (a general microglial biomarker), COX-2 (an M1-microglial biomarker), CD206 (an M2-microglial biomarker), GFAP (a general astrocytal biomarker), C3 (an A1-astrocytal biomarker), S100α10 (an A2-astrocytal biomarker), as well as pro-inflammatory cytokines IL-6, IL-1β, IFN-γ and TNF-α. Stress exposure also persistently upregulated the brain expression of several key apoptotic (Bax, Caspase-3, Bcl-2) and epigenetic genes (DNMT3a, DNMT3b, HAT1, HDAC4) in these fish. Collectively, the present model not only successfully recapitulates lasting behavioral and endocrine symptoms of clinical stress-related disorders, but also implicates changes in neuroglia, neuroinflammation, apoptosis and epigenetic modulation in long-term effects of stress pathogenesis in vivo.

Язык оригиналаанглийский
Номер статьи112644
ЖурналBehavioural Brain Research
Том389
Ранняя дата в режиме онлайн25 апр 2020
DOI
СостояниеОпубликовано - 1 июл 2020
Опубликовано для внешнего пользованияДа

Fingerprint Подробные сведения о темах исследования «Delayed behavioral and genomic responses to acute combined stress in zebrafish, potentially relevant to PTSD and other stress-related disorders: Focus on neuroglia, neuroinflammation, apoptosis and epigenetic modulation». Вместе они формируют уникальный семантический отпечаток (fingerprint).

Цитировать