Berberine attenuates SPS-induced cognitive and affective deficits and corticolimbic injury in Wistar rats via restoration of BDNF and redox-inflammatory balance.
Godson Emeka Anyanwu, Precious E Ekwueme, Ayugha Nsan, Lilian Ezeugwu, Prisca Chiamaka Ogbe, Chinyere N Anyanwu, Vivian O Ojiakor, Chima Paul Okechukwu Ugwu
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引用次数: 0
Abstract
Background: Single prolonged stress (SPS) is a validated PTSD-like paradigm that causes cognitive and affective dysfunction and corticolimbic injuries due to the dysregulation of the HPA-axis and neurotrophic, redox, and neuroimmune pathways. Berberine is a bioactive isoquinoline alkaloid that demonstrates neuroprotective effects, although its effect on corticolimbic-pathology caused by SPS is yet to be fully characterized.
Objectives: To ascertain whether berberine attenuates SPS-induced neurobehavioral impairments and corticolimbic neuronal damage in Wistar rats.
Methods: Adult male Wistar rats were exposed to SPS (restraint, forced swim, and anesthetic-induced loss of consciousness) and left undisturbed for 7 days to allow stress consolidation. Then, rats were given oral berberine (50 or 200 mg/kg) or fluoxetine (10 mg/kg) in a single daily dose. Behavioral measures were Y-maze spontaneous alternation, Morris water maze, novel object recognition and sucrose preference. ELISA was used to quantify serum corticosterone. BDNF, SOD, catalase, MDA, and IL-1b/IL-6/TNF-a were assayed in the hippocampus and mPFC. CFV and NeuN immunohistochemistry were used to assess neuronal integrity and astrocytic reactivity was assessed using GFAP-immunoreactivity.
Results: SPS induced severe deficits in working memory, spatial and recognition memories and reward sensitivity, and high basal corticosterone. It increased lipid peroxidation and pro-inflammatory cytokines while reducing antioxidant enzyme activities in brain tissue homogenates (hippocampus and medial prefrontal cortex). Berberine improved behavioral outcomes and attenuated endocrine, biochemical, and histopathological abnormalities in a dose-dependent manner.
Conclusion: Berberine attenuates SPS-induced-cognitive/affective dysfunction and corticolimbic-lesion and establishes normalization of basal corticosterone, BDNF recovery, antioxidant defense, lipid peroxidation, cytokine elevations, and astrocytic activation. These findings support berberine as a multi-target candidate for mitigating stress-related-neurotoxicity.
期刊介绍：
Nutritional Neuroscience is an international, interdisciplinary broad-based, online journal for reporting both basic and clinical research in the field of nutrition that relates to the central and peripheral nervous system. Studies may include the role of different components of normal diet (protein, carbohydrate, fat, moderate use of alcohol, etc.), dietary supplements (minerals, vitamins, hormones, herbs, etc.), and food additives (artificial flavours, colours, sweeteners, etc.) on neurochemistry, neurobiology, and behavioural biology of all vertebrate and invertebrate organisms. Ideally this journal will serve as a forum for neuroscientists, nutritionists, neurologists, psychiatrists, and those interested in preventive medicine.
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