Abstract
Systemic lipopolysaccharide (LPS) triggers neuroinflammation with consequent development of behavioral and cognitive deficits. Neuroinflammation plays a crucial role in the pathogenesis of neurodegenerative disorders including Alzheimer’s disease (AD). Berberine is an isoquinoline alkaloid in Berberis genus with antioxidant and anti-inflammatory property and protective effects in neurodegenerative disorders. In this research, beneficial effect of this alkaloid against LPS-induced cognitive decline was assessed in the adult male rats. LPS was intraperitoneally administered at a dose of 1 mg/kg to induce neuroinflammation and berberine was given via gavage at doses of 10 or 50 mg/kg, one h after LPS, for 7 days. Treatment of LPS group with berberine at a dose of 50 mg/kg (but not at a dose of 10 mg/kg) improved spatial recognition memory in Y maze, performance in novel object recognition task (NORT), and prevented learning and memory dysfunction in passive avoidance tasks. Furthermore, berberine lowered hippocampal activity of acetylcholinesterase (AChE), malondialdehyde (MDA), protein carbonyl, activity of caspase 3, and DNA fragmentation and improved antioxidant capacity through enhancing glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione (GSH). Besides, berberine attenuated inflammation-related indices, as was evident by lower levels of nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6). Berberine also appropriately restored hippocampal 3-nitrotyrosine (3-NT), cyclooxygenase 2 (Cox 2), glial fibrillary acidic protein (GFAP), sirtuin 1, and mitogen-activated protein kinase (p38 MAPK) with no significant alteration of brain-derived neurotrophic factor (BDNF). In summary, berberine could partially ameliorate LPS-induced cognitive deficits via partial suppression of apoptotic cascade, neuroinflammation, oxido-nitrosative stress, AChE, MAPK, and restoration of sirtuin 1.
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Abbreviations
- 3-NT:
-
3-nitrotyrosine
- AChE:
-
acetylcholinesterase
- AD:
-
Alzheimer’s disease
- BDNF:
-
brain-derived neurotrophic factor
- Cox 2:
-
cyclooxygenase 2
- GFAP:
-
glial fibrillary acidic protein
- GSH:
-
glutathione
- GPx:
-
glutathione peroxidase
- IL-6:
-
interleukin 6
- LPS:
-
lipopolysaccharide
- MDA:
-
malondialdehyde
- MAPK:
-
mitogen-activated protein kinase
- NF-κB:
-
nuclear factor-kappa B
- NORT:
-
novel object recognition task
- RNS:
-
reactive nitrogen species
- ROS:
-
reactive oxygen species
- Sirt 1:
-
sirtuin 1
- SOD:
-
superoxide dismutase
- TLR4:
-
toll-like receptor 4
- TNFα:
-
tumor necrosis factor α
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This research project was the result of MD thesis project (Sepideh Sadraie), approved and financially supported in part by Shahed University in 2016.
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Sadraie, S., Kiasalari, Z., Razavian, M. et al. Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms. Metab Brain Dis 34, 245–255 (2019). https://doi.org/10.1007/s11011-018-0349-5
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DOI: https://doi.org/10.1007/s11011-018-0349-5