Agmatine modulates anxiety and depression-like behaviour in diabetic insulin-resistant rats

Kale, Mayur B.; Nimje, Nitin; Aglawe, Manish M.; Umekar, Milind J.; Taksande, Brijesh G.; Kotagale, Nandkishor R.

doi:10.1016/j.brainres.2020.147045

Cited by 25 publications

(19 citation statements)

References 68 publications

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“…Pearson correlations between sucrose preference and interaction time (social behaviour) (a), between the latency to feed (novelty-suppressed feeding test) and immobility time (tail suspension test) (b), between , and between immobility time (tail suspension test)or forced swim test and TNF-α (d) immobility time in the tail suspension test, showing depressive-like behaviour. In support of these findings, several studies have reported that high-fat diet-induced type 2 diabetes increased depression-like behaviour in rats or mice by increasing immobility time in the tail suspension test and forced swim test (Kale et al, 2020;Nakhate et al, 2016;Soliman et al, 2020). On the other hand, we did not find any significant alterations in the social behaviour of diabetic mice compared to no-diabetic mice.…”

Section: Discussionsupporting

confidence: 90%

Swimming exercise decreases depression‐like behaviour and inflammatory cytokines in a mouse model of type 2 diabetes

Gilak-Dalasm

Peeri

Azarbayjani

2021

Experimental Physiology

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Clinical and experimental studies have shown that type 2 diabetes is associated with depression-related disorders. Inflammation has been identified as a common mechanism in both type 2 diabetes and depression. Several studies have suggested that swimming exercise might be able to reduce depression-related symptoms. The present study aimed to explore whether swimming exercise can decrease depressionlike behaviour in type 2 diabetic mice. To induce type 2 diabetes, male C57BL6 mice were treated with a high-fat diet and streptozocin. Type 2 diabetic animals were subjected to swimming exercise for 4 weeks. Then, depression-like behaviours were evaluated by sucrose preference, novelty-suppressed feeding, social interaction and tail suspension tests. We also measured levels of glucose, insulin and pro-inflammatory cytokines such as interleukin-1β and tumour necrosis factor-α in the serum of animals.The results indicated that type 2 diabetes significantly increased anhedonia-and depression-like behaviours in mice. We also found significant increases in glucose, insulin and inflammatory cytokines in diabetic mice. Moreover, swimming exercise reduced anhedonia-and depression-like behaviour in type 2 diabetic mice. Swimming exercise also decreased glucose and inflammatory cytokines in the serum of mice with type 2 diabetes. Collectively, this study demonstrates that swimming exercise decreased depression-like behaviour by reducing inflammation in type 2 diabetic mice.Further clinical studies are needed to validate these findings in patients with type 2 diabetes.

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Section: Discussionsupporting

confidence: 90%

Swimming exercise decreases depression‐like behaviour and inflammatory cytokines in a mouse model of type 2 diabetes

Gilak-Dalasm

Peeri

Azarbayjani

2021

Experimental Physiology

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“…45 BDNF is a target gene of Nrf2, 46 and Nrf2/BDNF signaling is involved in the antidepressant-like effect produced by agmatine and fluoxetine. 47 In our study, we found that the decreased BDNF expression was congruent with that of Nrf2 in the brain at 28 days after c-ICH, and that the decrease could be reversed by TP-500. Our results demonstrate that TP-500 can effectively reduce pro-inflammatory cytokines (such as IL-6, TNF-a) and ROS levels.…”

Section: Hypothesizedsupporting

confidence: 60%

Nrf2-BDNF-TrkB pathway contributes to cortical hemorrhage-induced depression, but not sex differences

Ren

Han

Liu

et al. 2021

J Cereb Blood Flow Metab

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Post-stroke depression, observed in 30-50% of stroke patients, negatively affects quality of life and mortality. The pathogenesis of post-stroke depression is complex, but heightened reactive oxygen species production and inflammation might be two key factors. We have reported that intracerebral hemorrhage (ICH) in cerebral cortex produces depression-like behavior in young male mice. Here, we found that mice lacking nuclear factor erythroid-derived 2-related factor 2 (Nrf2), a transcription factor that upregulates antioxidant proteins and trophic factors such as brain-derived neurotrophic factor (BDNF), had more severe depression-like behavior than wild-type mice at days 21 to 28 after cortical ICH (c-ICH). Moreover, the expression of Nrf2, heme oxygenase-1, BDNF, and TrkB were significantly decreased in wild-type mice after c-ICH. Interestingly, TP-500 (2 mg/kg), a potent Nrf2 inducer, decreased the inflammatory response and reactive oxygen species production on day 28 after c-ICH and improved depression-like behaviors. TrkB receptor antagonist ANA-12 abolished this anti-depression effect. Depression was more severe in female than in male wild-type mice after ICH, but TP-500 improved depression-like behavior in females. These results suggest that downregulation of Nrf2-BDNF-TrkB signaling contributes to development of post-stroke depression, and that Nrf2 inducer TP-500 might improve depression after c-ICH.

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“…These parameters were inhibited by agmatine treatment in the last 4 wk of the protocol. In this study, agmatine levels in the hippocampus of rats subjected to the T2DM protocol were significantly lower than those in the control animals[ 79 ].…”

Section: Beyond Mtorc1 Hypothesismentioning

confidence: 98%

“…Agmatine also exhibits anti-inflammatory effects in other disease models. In particular, in a type 2 diabetes mellitus (T2DM) model induced by a high-fat diet for 12 wk, anxiety- and depressive-like behaviors were associated with an increase in pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as a decrease in the BDNF immunocontent in the rat hippocampus[ 79 ]. These parameters were inhibited by agmatine treatment in the last 4 wk of the protocol.…”

Section: Beyond Mtorc1 Hypothesismentioning

confidence: 99%

Agmatine as a novel candidate for rapid-onset antidepressant response

Valverde¹,

Camargo²,

Rodrigues³

2021

WJP

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Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.

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Agmatine modulates anxiety and depression-like behaviour in diabetic insulin-resistant rats

Cited by 25 publications

References 68 publications

Swimming exercise decreases depression‐like behaviour and inflammatory cytokines in a mouse model of type 2 diabetes

Swimming exercise decreases depression‐like behaviour and inflammatory cytokines in a mouse model of type 2 diabetes

Nrf2-BDNF-TrkB pathway contributes to cortical hemorrhage-induced depression, but not sex differences

Agmatine as a novel candidate for rapid-onset antidepressant response

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