Validation of the Wistar-kyoto Rat Kept in Solitary Housing as an Animal Model for Endogenous Depression Using Voxel-based Morphometry
Validation of the Wistar-kyoto Rat Kept in Solitary Housing as an Animal Model for Endogenous Depression Using Voxel-based Morphometry
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DOI：
10.21203/rs.3.rs-612118/v1
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Takanobu Yoshii;N. Oishi;Yasutaka Sotozono;Anri Watanabe;Y. Sakai;Shunji Yamada;K. Matsuda;
中科院分区：
文献类型：
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作者：
Takanobu Yoshii;N. Oishi;Yasutaka Sotozono;Anri Watanabe;Y. Sakai;Shunji Yamada;K. Matsuda;
重度抑郁症是一种常见的精神疾病，通常对药物有抵抗力。Wistar-Kyoto（WKY）大鼠被认为是内源性抑郁症的动物模型;然而，将动物模型中获得的结果转化为人类是具有挑战性的。独居是一种温和的压力模式，可以模拟抑郁症患者的环境，由于症状而限制了社会活动。我们使用基于体素的形态学直接比较独居WKY大鼠模型与以前的人类研究的数据，并验证了我们的结果与行为研究和相关性分析。在腹侧海马、尾壳核、外侧隔、小脑蚓部和小脑核中检测到WKY大鼠的萎缩（p < 0.05，校正了家族错误率）。此外，自发行为与海马萎缩呈负相关，与小脑蚓部萎缩呈正相关。脑萎缩的区域验证了WKY大鼠作为内源性抑郁症的动物模型，并可以帮助将研究结果转化为人类。我们的研究还揭示了小脑导致抑郁症的可能性。
Major depressive disorder is a common psychiatric condition that is often resistant to medication. The Wistar-Kyoto (WKY) rat has been suggested as an animal model of endogenous depression; however, it is challenging to translate results obtained in animal models into humans. Solitary housing is a mild stress paradigm that could simulate the environment of depressive patients with limited social activity due to symptoms. We used voxel-based morphometry to directly compare the solitary-housed WKY rat model with data from previous human studies, and validated our results with behavioural studies and correlation analyses. Atrophy in WKY rats was detected in the ventral hippocampus, caudate putamen, lateral septum, cerebellar vermis, and cerebellar nuclei (p < 0.05, corrected for family-wise error rate). Further, locomotor behaviour was negatively correlated with hippocampal atrophy and positively correlated with atrophy of the cerebellar vermis. The regions of brain atrophy validate WKY rats as an animal model for endogenous depression and can aid the translation of study results to humans. Our study also reveals the possibility of a cerebellar contribution to depression.