Starch-enriched diet modulates the glucidic profile in the rat colonic mucosa

Purpose. The protective function of the intestinal mucosa largely depends on carbohydrate moieties that as a part of glycoproteins and glycolipids form the epithelial glycocalyx or are secreted as mucins. Modifications of their expression can be induced by an altered intestinal microenvironment and have been associated with inflammatory disorders and colorectal cancer. Given the influence of dietary factors on the gut ecosystem, here we have investigated whether a long term feeding on a starch-rich diet can modulate the glucidic profile in the colonic mucosa of rats. Methods. Animals were divided into two groups and maintained for 9 months at different diets: one group was fed a standard diet, the second was fed a starch-enriched diet. Samples of colonic mucosa, divided in proximal and distal portions, were processed for microscopic analysis. Conventional stainings and lectin histochemistry were applied to identify acidic glycoconjugates and specific sugar residues in oligosaccharide chains, respectively. Some lectins were applied on adjacent sections after sialidase/fucosidase digestion, deacetylation, and oxidation to characterize either terminal dimers or sialic acid acetylation. Results. An increase in sulfomucins was found to be associated with the starch-enriched diet that affected also the expression of several sugar residues as well as fucosylated and sialylated sequences in both proximal and distal colon. Conclusions. Although the mechanisms leading to such a modulation are at present unknown, either an altered intestinal microbiota or a dysregulation of glycosylation patterns might be responsible for the types and distribution of changes in the glucidic profile here observed

Neuroinflammatory Markers in Spontaneously Hypertensive Rat Brain: An Immunohistochemical Study

BACKGROUND: Spontaneously hypertensive rats (SHR) represent a model of hypertension and vascular injury. In the past decade, SHR were also considered as a model of vascular dementia. Several studies have shown that cerebrovascular changes in SHR may mimic brain vascular diseases of hypertensive individuals. Vascular and cerebrovascular changes during hypertension are often linked to inflammatory processes. Inflammation frequently affects vascular endothelium, perivascular astrocytes that form blood brain barrier. This inflammatory reaction may lead to neuro-inflammation with consequent damage of brain tissue. A significant brain atrophy, a reduction of white matter volumes, and BBB dysfunction were found in SHR. Micro- and macrogliosis in deep cortical regions were also observed. Based on these findings, this study was designed to define neuroinflammation entity in SHR, using immunohistochemistry technique for different inflammatory markers. METHODS: Thirty-two-week-old SHR and age-matched Wistar Kyoto rats were used. Brain was processed for immunohistochemistry. Astrogliosis markers for astrocytes (glial fibrillary acidic protein) and microglia (isolectin IB4) were used. The pro-inflammatory interleukins (IL-1b, IL-6) and tumor necrosis factor alpha (TNFa) expression were also evaluated. RESULTS: In SHR brain, an obvious glial reaction was found both for GFAP-immunoreactive astrocytes and for microglia. The pro-inflammatory IL-1b was significantly increased in CA1 sub-field of SHR hippocampus. The TNFa expression was higher in frontal cortex of SHR compared to WKY. CONCLUSION: The above neuromorphological evidences indicate that SHR are predictive animal models for vascular brain disorders and neuroinflammation. Furthermore, this model may be useful to evaluate anti-inflammatory and neuroprotective effects of different molecules

Effects of choline containing phospholipids on the neurovascular unit: A review

The roles of choline and of choline-containing phospholipids (CCPLs) on the maintenance and progress of neurovascular unit (NVU) integrity are analyzed. NVU is composed of neurons, glial and vascular cells ensuring the correct homeostasis of the blood-brain barrier (BBB) and indirectly the function of the central nervous system. The CCPLs phosphatidylcholine (lecithin), cytidine 5'-diphosphocholine (CDP-choline), choline alphoscerate or α-glyceryl-phosphorylcholine (α-GPC) contribute to the modulation of the physiology of the NVU cells. A loss of CCPLs contributes to the development of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease. Our study has characterized the cellular components of the NVU and has reviewed the effect of lecithin, of CDP-choline and α-GPC documented in preclinical studies and in limited clinical trials on these compounds. The interesting results obtained with some CCPLs, in particular with α-GPC, probably would justify reconsideration of the most promising molecules in larger attentively controlled studies. This can also contribute to bett

Metabolic syndrome, hypertension, and nervous system injury: Epidemiological correlates

Metabolic syndrome (MetS) is a common and complex disorder combining hypertension, obesity, dyslipidemia, and insulin resistance. MetS represents a risk factor for changes in cognitive functions in older age, and several studies have suggested that MetS may be linked to dementia. This article reviews the main evidences about the relationship between MetS and neurodegenerative disease. Starting from an epidemiological point of view, the article analyzes medico-social aspects related to MetS, considering the reduction of work capacity and the condition of disability that it involves. Some authors affirm that on the basis of current Italian legislation, it is possible to consider the syndrome as a disability. This is because all the diseases that make up MetS are high-risk clinical pathological conditions. For these reasons, a joint action is required to contain the incidence of MetS, the high social costs, and the loss of productivity related to the syndrome. In conclusion, healthcare initiatives could be adopted in order to increase the understanding of the pathogenic contributions of each element on MetS and how they can be modified. These actions will be useful to reduce healthcare costs and can lead to more effective prevention of metabolic disease, thus promoting good health. Abbreviations: MetS: Metabolic syndrome; WHO: World Health Organization; CVD: cerebrovascular diseases; AD: Alzheimer's Disease; VaD: Vascular Dementia; IDF: International Diabetes Federation; T2DM: type 2 diabetes mellitus; CAD: coronary artery disease; MCI: mild cognitive impairment; NCDs: Non Communicable Diseases; BMI: Body Mass Index; ICIDH: International classification of impairments, disabilities and handicaps

Obesity-related blood brain barrier changes in obese Zucker rats

The blood brain barrier (BBB) is the site of exchange between blood and the nervous tissue. Damage of it may impair physiological balance between blood stream and nervous tissue. Metabolic syndrome (MetS) is defined by several interconnected physiological, biochemical, and metabolic factors directly related to obesity. It increases the risk of atherosclerotic cardiovascular and cerebrovascular disease and of all cause mortality. Obese Zucker rats (OZRs), with a mutation in leptin receptor, represent a model of obesity exhibiting diabetes and moderate arterial hypertension. In OZRs hyperglycaemia, hyperinsulinaemia and hyperlipidaemia occur simultaneously. This work had characterized BBB and endothelial alterations of OZRs compared to their non-obese cohort lean Zucker rats (LZRs) for assessing the occurrence of an eventual cerebrovascular injury. Brains of male OZRs and LZRs of 12, 16 and 20 weeks were processed for the immunochemical and immunohistochemical detection of different BBB markers. The water channel protein Aquaporin-4 (AQP4) and the glucose transporter protein- 1 (GLUT1) involved in the glucose passage across the BBB endothelial cells were investigated. The expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) was also assessed within cerebrovascular endothelium as a marker of inflammation. In intracerebral arteries of older OZRs, a decrease of lumen area with an increase of wall area was found. BBB of older OZRs revealed an augmented expression of AQP4 probably related to an edema formation. A downregulation of GLUT1 was observed in OZRs of 12 weeks of age. This may represent the adaptive reaction to prevent excessive glucose entering in neurons. On the contrary, in older OZRs an obvious increase in the expression of GLUT1 was found. These phenomena are probably related to vascular inflammation as confirmed by the increase of ICAM-1 and VCAM-1 expression in the endothelium of older OZRs. The above evidence shows that OZRs develope specific BBB changes. This could contribute to clarify the pathophysiology of nervous system damage reported in obese individuals. OZRs may represent an useful animal model for assessing the influence of obesity/MetS on the brain and the possible correlation of it with neurodegenerative disorders

Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain

Choline is involved in relevant neurochemical processes. In particular, it is the precursor and metabolite of acetylcholine (ACh). Choline is an essential component of different membrane phospholipids that are involved in intraneuronal signal transduction. On the other hand, cholinergic precursors are involved in ACh release and carry out a neuroprotective effect based on an anti-inflammatory action. Based on these findings, the present study was designed to evaluate the effects of choline and choline precursor (Choline alphoscerate, GPC) in the modulation of inflammatory processes in the rat brain. Male Wistar rats were intraperitoneally treated with 87 mg of choline chloride/kg/day (65 mg/kg/day of choline), and at choline-equivalent doses of GPC (150 mg/kg/day) and vehicle for two weeks. The brains were dissected and used for immunochemical and immunohistochemical analysis. Inflammatory cytokines (Interleukin-1β, IL-1β; Interleukin-6 , IL-6 and Tumor Necrosis Factor-α, TNF-α) and endothelial adhesion molecules (Intercellular Adhesion Molecule, ICAM-1 and Vascular cell Adhesion Molecule, VCAM-1) were studied in the frontal cortex, hippocampus, and cerebellum. The results clearly demonstrated that treatment with choline or GPC did not affect the expression of the inflammatory markers in the different cerebral areas evaluated. Therefore, choline and GPC did not stimulate the inflammatory processes that we assessed in this study

Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats

Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/-)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage

Age-related changes in the brain of obese Zucker rat: Morphological and immunochemical analysis.

Metabolic syndrome (MetS) is defined as a combination of glucose intolerance, arterial hypertension, dyslipidemia and obesity with insulin resistance as the main cause of these imbalances. In general, obesity increases the risk of vascular diseases. Both cardiovascular and cerebrovascular disorders are often linked to impaired cognitive functions. A relationship between metabolic disease and mild cognitive impairment, and/or vascular dementia was hypothesized. The obese Zucker rat (OZR), represents a model of obesity and type 2 diabetes exhibiting a moderate degree of arterial hypertension. OZRs are characterized by the simultaneous occurrence of hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. This study has investigated brain microanatomy of OZRs compared with their nonobese cohort lean Zucker rats (LZRs) to assess possible relationships between MetS and brain damage. Male OZRs and LZRs of 12, 16 and 20 weeks of age were used. Body weight, blood pressure and blood chemistry parameters were checked every two weeks and before killing. The brain was dissected out and processed for immunochemical and immunohistochemical analysis of nerve cells identified by neuronal specific nuclear protein (NeuN) and axons identified by neurofilament (NF) immunohistochemistry. Glial-fibrillary acid protein (GFAP) immunoreactive astrocytes were also investigated. OZRs of different ages, were characterized by a high body weight, an increase of systolic pressure, glycemia, triglycerides and cholesterol levels in comparison with LZRs. An age-dependent increase of these parameters was observed in OZRs. A decrease of brain/body weight ratio was found in OZRs. In frontal cortex and hippocampus, morphological and immunochemical analysis revealed a decrease of NeuN immunoreactive neurons not related to apoptosis in older OZRs group compared to age matched LZRs. In OZRs a decrease of NF immunoreaction and an increase of GFAP immunoreactive astrocytes was observed compared to LZRs These findings suggest that OZRs, used for investigating mechanisms and pathophysiology of obesity and type 2 diabetes, may also represent a model for assessing the influence of MetS on brain

Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential

The molecular nature of lipoic acid (LA) clarifies its capability of taking part to a variety of biochemical reactions where redox state is meaningful. The pivotal action of LA is the antioxidant activity due to its ability to scavenge and inactivate free radicals. Furthermore, LA has been shown to chelate toxic metals both directly and indirectly by its capability to enhance intracellular glutathione (GSH) levels. This last property is due to its ability to interact with GSH and recycle endogenous GSH. LA exhibits significant antioxidant activity protecting against oxidative damage in several diseases, including neurodegenerative disorders. Interestingly, LA is unique among natural antioxidants for its capability to satisfy a lot of requirements, making it a potentially highly effective therapeutic agent for many conditions related with oxidative damage. In particular, there are evidences showing that LA has therapeutic activity in lowering glucose levels in diabetic conditions. Similarly, LA supplementation has multiple beneficial effects on the regression of the mitochondrial function and on oxidative stress associated with several diseases and aging