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Fish oil prevents rodent anxious states comorbid with diabetes: A putative involvement of nitric oxide modulation
Isadora Pozzetti Siba1, Mariza Bortolanza2, Maria Aparecida Barbato Frazão Vital1
1Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
Abstract:
There is an urgent need to understand the pathophysiological mechanisms related to anxiety associated with diabetes, seeking more effective alternative treatments to treat it. For that, the effect of a preventive and prolonged treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, was tested in streptozotocin-diabetic (DBT) rats submitted to the anxiety tests. Additionally, an immunohistochemistry for neuronal NO synthase (nNOS) was performed in brain areas related to anxiety, such as lateral amygdala (AMY), hippocampus (HIP) and dorsolateral periaqueductal gray (dlPAG). Lastly, the effect of NO precursor L-arginine (L-Arg) or nNOS inhibitor 7-nitroindazole (7-NI) was tested in DBT animals treated with vehicle (VEH) or FO. Our data demonstrated that vehicle-treated DBT animals exhibited a more pronounced anxiogenic-like response and also presented high nNOS levels in the AMY, HIP and rostral dlPAG, what were both significantly prevented by FO treatment. This treatment was able to prevent the impairment in locomotor activity besides improving the high glycemic levels in DBT rats. Interestingly, while injection of 7-NI or L-Arg in VEH-treated DBT animals induced an anxiogenic-like and anxiolytic-like effect, respectively; the previous treatment with both L-Arg and 7-NI in FO-DBT animals abolished the anxiolytic-like effect induced by FO treatment. Altogether, our data support the hypothesis that a dysregulation in the NO production in brain areas as AMY, HIP and dlPAG may contribute to the mechanisms that link anxiety and diabetes, and the prevention of nNOS brain expression changes induced by a prolonged treatment with FO may be an important mechanism related to its anxiolytic-like effect.
Insights
Fish oil (FO) treatment prevented anxiety-like behaviors and normalized high neuronal nitric oxide synthase (nNOS) levels in diabetic rats. This suggests FO
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is frequently associated with anxiety disorders, necessitating research into underlying mechanisms and alternative treatments.
- Omega-3 polyunsaturated fatty acids, particularly from fish oil (FO), are recognized for their anti-inflammatory and neuroprotective properties.
- Nitric oxide (NO) signaling pathways in specific brain regions are implicated in the pathophysiology of anxiety.
Purpose of the Study:
- To investigate the effects of preventive, prolonged fish oil (FO) treatment on anxiety-like behaviors in streptozotocin-induced diabetic (DBT) rats.
- To examine the expression of neuronal nitric oxide synthase (nNOS) in brain areas associated with anxiety (amygdala, hippocampus, periaqueductal gray).
- To elucidate the role of the NO pathway by testing L-arginine (L-Arg) and 7-nitroindazole (7-NI) in FO-treated diabetic rats.
Main Methods:
- Streptozotocin-induced diabetic (DBT) rats received prolonged preventive treatment with fish oil (FO) or vehicle (VEH).
- Anxiety-like behaviors were assessed using standard behavioral tests.
- Immunohistochemistry was used to quantify nNOS expression in the lateral amygdala (AMY), hippocampus (HIP), and dorsolateral periaqueductal gray (dlPAG).
- The effects of L-arginine (L-Arg) and 7-nitroindazole (7-NI) were evaluated in VEH- and FO-treated DBT rats.
Main Results:
- Vehicle-treated DBT rats exhibited increased anxiety-like behavior and elevated nNOS levels in the AMY, HIP, and dlPAG.
- FO treatment significantly prevented these behavioral and neurochemical changes in DBT rats, also improving locomotor activity and glycemic levels.
- In VEH-treated DBT rats, 7-NI induced anxiogenic-like effects, while L-Arg produced anxiolytic-like effects. In FO-treated DBT rats, both L-Arg and 7-NI abolished the anxiolytic-like effect of FO.
Conclusions:
- Dysregulation of NO production in the AMY, HIP, and dlPAG contributes to the anxiety associated with diabetes.
- Prolonged FO treatment exerts anxiolytic-like effects, potentially by preventing alterations in brain nNOS expression.
- The NO pathway is crucial for the observed anxiolytic-like effects of FO in diabetic rats, highlighting a potential therapeutic target.
