Study on the mechanism of losartan reducing the risk of comorbid depression in epileptic rats
Journal Title: Chinese Journal of Nervous and Mental Diseases - Year 2024, Vol 50, Issue 2
Abstract
[Objective] To investigate the effectiveness and mechanisms of losartan in improving comorbid depression in epileptic rats. [Methods] Male rats were randomly divided into three groups: The losartan-pilocarpine group (PL-L) received intraperitoneal injection of lithium-pilocarpine to establish the epilepsy model, and then followed by losartan intervention. The pilocarpine group (PL) received intraperitoneal injection of lithium-pilocarpine to establish the epilepsy model. The control group (Ctrl) received intraperitoneal injection of lithium chloride. We used the body weight gain and sucrose preference test to analyze the behavior of rats in each group, and RT-PCR was used to examine the expression of High mobility group protein B1 (HMGB1)、interleukin-1β (IL-1β) and interleukin-6 (IL-6) mRNA in hippocampus of rats in each group. [Results] Compared to the Ctrl group, rats in the PL group showed significantly decreased body weight gain [(12.68±5.23) g vs. (41.08±15.87) g, P<0.01] and sucrose preference rate (53.85%±10.14% vs. (88.56%±16.53%, P<0.01). The expression of HMGB1 mRNA (4.17±1.23 vs. 1.00±0.02, P<0.01) was significantly increased. The expression of IL-1β (4.95±1.67 vs. 1.02±0.27, P<0.01) and IL-6 (2.75±1.20 vs. 1.01±0.19, P<0.05) were significantly increased too. Compared with the PL group, rats in the PL group showed significantly increased body weight gain [(37.97±10.24) g vs. (12.68±5.23) g, P<0.01] and sucrose preference rate (77.50%±7.35% vs. 53.85%±10.14%, P<0.05). The expression of HMGB1 (0.76±0.27 vs. 4.17±1.23, P<0.01) was significantly decreased. The expression of IL-1β (0.67±0.21 vs. 4.95±1.67, P<0.01) and IL-6 (0.95±0.27 vs. 2.75±1.20, P<0.05) mRNA were significantly decreased too. [Conclusion] Losartan can reduce the incidence of comorbid depression in epileptic rats, The possible mechanism is that losartan reduces HMGB1 release, so as to reduce the inflammatory factors (IL-1β, IL-6) in the hippocampus of rats. It can reduce the incidence of depression like behavior disorder in rats with epilepsy.
Authors and Affiliations
Nannan PAN, Yachun HU, Xuezhen LIAO, Zhe SHI, Haishan SHI
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