Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan.
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan; Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, Ohtawara, Tochigi 324-8501, Japan.
Neurosci Lett. 2024 Nov 1;842:137989. doi: 10.1016/j.neulet.2024.137989. Epub 2024 Sep 12.
The commonly used lipopolysaccharide (LPS)-induced depression models often evaluate depression-like behaviors in the acute phase after a single intraperitoneal injection of LPS, and are not suitable for examining long-term depression-like behaviors. To overcome this limitation, we developed a mice LPS model for elucidating the long-term pathophysiology of depression. Using the tail-suspension test, we show that a single intraperitoneal injection of a high dose (1.66 mg/kg) of LPS prolonged depression-like behavior to 14 days after LPS administration unlike 4 days after administration for the most commonly used LPS dose (0.83 mg/kg). Upon high-LPS dose administration, TNF-α levels in the cerebrospinal fluid were increased only on the first day after administration. Moreover, LPS-induced depression-like behavior on day 10 after LPS administration was prevented by imipramine or minocycline. Immunohistochemical analysis revealed reduced neurogenesis in the hippocampal dentate gyrus of LPS-treated mice on day 10 of LPS administration. The LPS model, in which a single intraperitoneal administration of LPS at a dose double of the standard dose used currently, exhibits depression-like behavior via reduced neurogenesis mediated by neuroinflammation, and should be useful for elucidating the long-term pathophysiology of depression and for studying antidepressant drugs.
常用的脂多糖（LPS）诱导的抑郁模型通常在单次腹腔注射 LPS 后的急性期评估类似抑郁的行为，不适合检查长期类似抑郁的行为。为了克服这一限制，我们开发了一种用于阐明抑郁长期病理生理学的小鼠 LPS 模型。使用悬尾试验，我们发现，与最常用的 LPS 剂量（0.83mg/kg）给药后 4 天相比，单次腹腔注射高剂量（1.66mg/kg）的 LPS 将类似抑郁的行为延长至 LPS 给药后 14 天。在给予高 LPS 剂量后，仅在给药后第 1 天脑脊液中的 TNF-α 水平增加。此外，在 LPS 给药后第 10 天，给予 LPS 诱导的类似抑郁行为可被丙咪嗪或米诺环素预防。免疫组织化学分析显示，在 LPS 给药后第 10 天，LPS 处理的小鼠海马齿状回中的神经发生减少。该 LPS 模型通过神经炎症介导的神经发生减少，单次腹腔内给予 LPS 剂量是目前标准剂量的两倍，表现出类似抑郁的行为，应有助于阐明抑郁的长期病理生理学，并研究抗抑郁药物。
