Ellagic Acid Inhibits Neuroinflammation and Cognitive Impairment Induced by Lipopolysaccharides
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ORIGINAL PAPER
Ellagic Acid Inhibits Neuroinflammation and Cognitive Impairment Induced by Lipopolysaccharides Guilherme Lopes Dornelles1 · Juliana Sorraila de Oliveira2 · Erin John Rieger de Almeida3 · Mello Camila Benaduce Emanuelli Mello1 · Bernardo Rodrigues e Rodrigues1 · Cássia Bagolin da Silva1 · Letícia dos Santos Petry4 · Micheli Mainardi Pillat2 · Taís Vidal Palma2 · Cinthia Melazzo de Andrade1,2 Received: 16 April 2020 / Revised: 15 July 2020 / Accepted: 27 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Neuroinflammation is a predisposing factor for the development of cognitive impairment and dementia. Among the new molecules that are currently being studied, ellagic acid (EA) has stood out for its neuroprotective properties. The present study investigated the effects of ellagic acid in the object recognition test, oxidative stress, cholinergic neurotransmission, glial cell expression, and phosphorylated Tau protein expression. For this, 32 male Wistar rats received an intraperitoneal (IP) application of lipopolysaccharides (LPS) at a dose of 250 µg/kg or 0.9% saline solution (SAL) for 8 days. Two hours after the IP injections, the animals received 100 mg/kg of EA or SAL via intragastric gavage. Behavioral parameters (open field test and object recognition) were performed on days 5, 6, and 7 of the experimental periods. The results showed that the treatment with EA in the LPS group was able to inhibit cognitive impairment, modulate the immune system response by significantly reducing glial cell expression, attenuating phosphorylated Tau and oxidative damage with consequent improvement in the antioxidant system, as well as preventing the increase of acetylcholinesterase activity. Thus, the neuroprotective effects of EA and its therapeutic potential in cognitive disorders secondary to neuroinflammation were demonstrated. Keywords Ellagic acid · Oxidative stress · Acetylcholinesterase · Microglia · Astrocytes · Rats
Introduction Neuroinflammation is a characteristic of several neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and acute traumatic brain injury [1–4]. Systemic administrations of lipopolysaccharides
* Guilherme Lopes Dornelles [email protected] 1
Departamento de Clínica de Pequenos Animais, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria, RS 97105‑900, Brazil
2
Departamento de Bioquímica, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105‑900, Brazil
3
Departamento de Educação Física, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105‑900, Brazil
4
Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS 97105‑900, Brazil
(LPS) have been described as experimental models that mimic the pathological disorders of these diseases, including AD-associated cholinergic neuronal degeneration. LPS can impair the consolidation of specific memory p
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