Histological and imunohistochemical alterations of hippocampus and prefrontal cortex in a rat model of Alzheimer like-disease with a preferential role of the flavonoid “hesperidin”

• Published in: Journal of molecular histology 2021-10, Vol.52 (5), p.1043-1065
• Main Authors: Mandour, Dalia A., Bendary, M. A., Alsemeh, Amira E.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Age; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Basal forebrain; Behavior, Animal; Biochemical analysis; Biomedical and Life Sciences; Biomedicine; Body Weight; Cell Biology; Developmental Biology; Disease Models, Animal; Flavonoids; Forebrain; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Glutathione; Glutathione - metabolism; Hesperidin; Hesperidin - pharmacology; Hippocampus; Hippocampus - pathology; IL-1β; Immunohistochemistry; Inflammation; Interleukin 10; Life Sciences; Male; Malondialdehyde; Malondialdehyde - metabolism; Neurodegeneration; Neurodegenerative diseases; Neuroprotection; Organ Size; Original Paper; Oxidative stress; Phosphorylation; Prefrontal cortex; Prefrontal Cortex - pathology; Proteins; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; Rats; Rats, Sprague-Dawley; Scopolamine; Spatial memory; Synaptophysin; Synaptophysin - metabolism; Tau protein; tau Proteins - metabolism; Tumor necrosis factor-α
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-021-09998-6

Alzheimer’s disease (AD) is a chronic age-related neurodegenerative disease characterized by degeneration of the central cholinergic neurons, inflammation and oxidative stress in the basal forebrain, prefrontal cortex and hippocampus. Hesperidin (Hesp) is one of the flavonoids havinganti-inflammatory and anti-oxidative properties in some neurodegerative brain lesions. To investigate the possible neuroprotective role of Hespin an AD-like rat model induced experimentally by Scopolamine (Scop). Forty adult male Sprague Dawley rats were randomly allocated into four groups. Group I—(Control), group II—(Hesp) (supplemented orally with 100 mg/kg Hesp for 28 days), group III—(AD) (injected i.p with 1 mg/kg Scop for 9 days) and group IV—(Hesp/AD). At the end of the experiment, behavioral (Y-maze test) and biochemical analysis were carried out along with histological, immunohistochemical and morphometric studies of the hippocampus and prefrontal cortex. AD rats displayed memory impairment in the behavioural paradigm with a concomitant increase of serum TNF-α and IL-1β, while IL-10 decreased significantly. Also, there was a rise of amyloid beta-42 (Aβ-42), acetylcholinesterase (AChE) activity and malondialdehyde (MDA) together with a decrease of reduced glutathione (GSH) in hippocampal and prefrontal homogenate. In addition, sections of the hippocampus and prefrontal cortex revealed obvious histopathological changes, overexpression of p-Tau protein and glial fibrillary acidic protein (GFAP) with a decrease in the expression of synaptophysin (SYN). Contradictorily, pre-treatment with Hesp offset the spatial memory deficits, redox imbalance, Aβ-42 and AChE over activity as well as preserved the histological architecture and attenuated the raised p-Tau protein and GFAP while upregulated SYN immuoreactivity of AD rats. Collectively, our results highlight the potential mitigating role of Hesp in AD-like state in rats and this may presumably raise the possibility of its future implementation as a prophylactic remedy against AD in humans. Graphic abstract