The effects of neuroinflammation induced by systemic lipopolysaccharides on the hippocampi of aged Sprague-Dawley rats

Abstract

Dementia affects a significant number of South Africans. In 2015, an estimated 186, 000 South Africans were recorded as being patients of this irreversible condition. Alzheimer’s disease (AD) accounts for 60% to 80% of reported dementia cases. It is estimated that more than 46.8 million people are affected by AD, worldwide. According to the 2015 World Alzheimer’s Report, an estimated 186,000 South Africans struggled with dementia in 2015, and this number is anticipated to increase to 275 000 by 2030. In the past decades, two hallmarks termed amyloidosis and taupathy have received major acknowledgement in neurodegenerative studies. Although this knowledge has tremendously contributed towards the understanding of the molecular mechanisms underlying AD, therapeutic treatments that reverse the disease are yet to be discovered. Therefore, exploring the aetiology of the disease using a popular rodent-model of inflammation can help provide some missing links required for long-term therapeutic strategies. Previous research has validated the use of lipopolysaccharide (LPS) in rodent models to replicate characteristics of AD and examine the inflammatory pathways and molecules involved. Therefore, in this study, the hippocampal region of male Sprague-Dawley rats was examined for AD-like (cognitive and histological) pathologies in response to repeated exposure to LPS. Subjects were assorted into one control group and three experimental groups, and the results of the experimental group were compared against the control group. LPS sourced from Escherichia coli 055:B5 was administered through repeated subcutaneous (SC) injection to induce a chronic systemic inflammatory response. Cognitive assesssments were conducted using a series of three behavioural experiments commonly used by researchers. This included the Y-maze, novel object recognition (NOR), and open-field tests. To quantitatively determine the effects of LPS-induced neuroinflammation on hippocampal neuroglia-astrocytes and microglia, biochemical assays involving ELISA and confocal microscopy were performed. To identify astrocytes and microglia, anti-glial fibrillary protein (GFAP) and anti-ionized calcium-binding adaptor molecule 1 (Iba1) fluorescent markers were used to stain hippocampal sections and view by microscopy. Previous findings have conveyed the benefits of honey as an anti-inflammatory agent against infectious pathogens. Therefore, during the experimental period of this study, Manuka honey was introduced to the subjects by oral gavage. The effects of honey as a “mopping agent” were identified by comparison of the experimental groups against the control group. Therefore the aim of this study was to investigate the effects of neuroinflammation induced by systemic lipopolysaccharide from Escherichia coli 055:B5 on the hippocampi of Sprague-Dawley rats. Cognitive assessments revealed that LPS exposure, over a 10-day period, did not significantly impair short-term spatial working memory, learning capacity and spontaneous memory, and anxiety, and locomotor activity. Confocal microscopy showed that LPS significantly increased the quantity of microglia detected by Iba1 antibody. This suggests that LPS exposure induced neuroinflammation in the hippocampal region, however, the nature of the inflammatory response, physiological or pathological, was unclear.