Antidepressant-like Effects of Renin Inhibitor Aliskiren in an Inflammatory Mouse Model of Depression.
Sami I AlzareaHassan H AlhassanAbdulaziz Ibrahim AlzareaZiad H Al-OanziMuhammad AfzalPublished in: Brain sciences (2022)
Depression is considered a neuropsychic disease that has global prevalence and is associated with disability. The pathophysiology of depression is not well understood; however, emerging evidence has indicated that neuroinflammation could contribute to developing depression symptoms. One of the factors that have a role in the development of neuroinflammation is the renin-angiotensin system. Therefore, the goal of the current study is to determine the antidepressant-like effects of Aliskiren, a renin inhibitor, against lipopolysaccharide (LPS)-induced depressive-like behavior in mice, glial cell activation, and the upregulation of proinflammatory cytokines in the prefrontal cortex. For behavioral studies, the open field test (OFT), tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT) were used. Inflammatory markers were assessed using real-time polymerase chain reaction (RT-PCR). LPS administration (0.5 mg/kg, intraperitoneal injection (i.p.)) sufficiently reduced the number of crossings in OFT, whereas Aliskiren pretreatment (10 mg/kg, i.p.) attenuated the LPS effect for two hours after LPS injection. The treatments did not show effects on locomotor activity in OFT 24 h after LPS administration. LPS increased the immobility time in TST and FST or reduced sucrose consumption in SPT after 24 h. Aliskiren reversed the effects induced by LPS in TST, FST, and SPT. CD11 b mRNA, a microglial marker, GFAP mRNA, an astroglial marker, and proinflammatory cytokines genes (TNF-α, IL-1β, and IL-6) were upregulated in the prefrontal cortex in LPS exposed animals. However, Aliskiren reduced LPS-induced inflammatory genes in the prefrontal cortex. Hence, the outcomes conclude that Aliskiren prevents depressive illness associated with neuroinflammation in humans.
Keyphrases
- lps induced
- inflammatory response
- prefrontal cortex
- lipopolysaccharide induced
- toll like receptor
- depressive symptoms
- sleep quality
- mouse model
- anti inflammatory
- major depressive disorder
- bipolar disorder
- oxidative stress
- traumatic brain injury
- rheumatoid arthritis
- stress induced
- cell proliferation
- type diabetes
- risk factors
- mesenchymal stem cells
- genome wide
- binding protein
- single cell
- dna methylation
- angiotensin converting enzyme
- cell therapy
- genome wide identification