Abstract
Hyperhomocysteinemia (hHcy) represents a strong risk factor for atherosclerosis-associated diseases, like stroke, dementia or Alzheimer’s disease. A methionine (Met)-rich diet leads to an elevated level of homocysteine in plasma and might cause pathological alterations across the brain. The hippocampus is being constantly studied for its selective vulnerability linked with neurodegeneration. This study explores metabolic and histo-morphological changes in the rat hippocampus after global ischemia in the hHcy conditions using a combination of proton magnetic resonance spectroscopy and magnetic resonance-volumetry as well as immunohistochemical analysis. After 4 weeks of a Met-enriched diet at a dose of 2 g/kg of animal weight/day, adult male Wistar rats underwent 4-vessel occlusion lasting for 15 min, followed by a reperfusion period varying from 3 to 7 days. Histo-morphological analyses showed that the subsequent ischemia-reperfusion insult (IRI) aggravates the extent of the sole hHcy-induced degeneration of the hippocampal neurons. Decreased volume in the grey matter, extensive changes in the metabolic ratio, deeper alterations in the number and morphology of neurons, astrocytes and their processes were demonstrated in the hippocampus 7 days post-ischemia in the hHcy animals. Our results suggest that the combination of the two risk factors (hHcy and IRI) endorses and exacerbates the rat hippocampal neurodegenerative processes.
Highlights
Methionine (Met) is an essential amino acid present in food, which is regularly consumed within the Western diet [1,2,3,4,5]
Determination of Plasma Homocysteine Level BiomoleculeAs 2n0a2l0y, s1i0s, 1o1f2p8 lasma level of Hcy in animals has shown that total plasma Hcy level in animal7sof 20 with 28 days of Met diet (Met-C) was significantly higher when compared to the naïve male control Wistar rats (7.08 ± 0.33 μmol/l, n = 5), and reached 11.22 ± 3.86 μmol/l (n = 5). 3.2
Our study utilizes a novel approach which combines histological analyses with the non-invasive in vivo 1H magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) methodology, with the aim to reveal the potential histo-morphological as well as the metabolic hippocampal dysregulation in rats with Met diet subjected to ischemia-reperfusion insult (IRI)
Summary
Methionine (Met) is an essential amino acid present in food, which is regularly consumed within the Western diet [1,2,3,4,5]. Protein intake rich in Met content or dysregulation of Met metabolism within the “Met-homocysteine” cycle can concomitantly lead to the elevation of homocysteine (Hcy) in the circulating plasma. Clinical relevance of elevated total Hcy level in plasma has been proven by many studies on different tissues [14,15]. It was shown that neuroinflammation followed by a significant increase of cognitive deficits and micro-haemorrhages were manifested on an established model of hHcy in mice by a restricted intake of B vitamins and enriched Met diet [16]. Development of the neurodegenerative disorders, such as progressive atherosclerosis and acute ischemic stroke, cognitive impairment, dementia, or Alzheimer’s disease (AD), were shown to be associated with hHcy [1,3,5], but the exact mechanism of its involvement in an affecting neuronal tissue is not yet elucidated
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