The Molecular and Functional Changes of Neural Stem Cells in Alzheimer's Disease: Can They be Reinvigorated to Conduct Neurogenesis.

Alzheimer's disease (AD) is considered one of the most complicated neurodegenerative disorders, and it is associated with progressive memory loss and remarkable neurocognitive dysfunction that negatively impacts the ability to perform daily living activities. AD accounts for an estimated 60-80% of dementia cases. AD's previously known pathological basis is the deposition of amyloid ß (Aß) aggregates and the formation of neurofibrillary tangles by tau hyperphosphorylation in the cell bodies of neurons that are located in the hippocampus, neocortex, and certain other regions of the cerebral hemispheres and limbic system. The lack of neurotransmitter acetylcholine and the activation of oxidative stress cascade may also contribute to the pathogenesis of AD. These pathological events can lead to irreversible loss of neuronal networks and the emergence of memory impairment and cognitive dysfunction that can engender an abnormal change in the personality. AD cannot be cured, and to some extent, the prescribed medications can only manage the symptoms associated with this disease. Several studies have reported that the regenerative abilities of neural stem/progenitor cells (NSCs) remarkably decline in AD, which disturbs the balancing power to control its progression. Exogenous infusion or endogenous activation of NSCs may be the ultimate solution to restore the neuronal networks in the brain of AD patients and regenerate the damaged areas responsible for memory and cognition. In this mini-review, we will touch upon the fate of NSCs in AD and the utilization of neurogenesis using modified NSCs to restore cognitive functions in AD.

Therapeutic Potential of Select Dietary Compounds in the Management of Hypertension and its Cardiovascular Complications.

Hypertension is a common risk factor for cardiovascular disease and mortality worldwide. Proper nutrition and diet are known to play an indispensable role in the treatment and management of hypertension. Bioactive compounds that occur in small quantities in foods such as onions, fish and red wine are being intensively studied to uncover their vasoprotective, antioxidant, anti-proliferative and anti-inflammatory effects which are beneficial to attenuate chronic disease and protect human health. In this article, the anti-hypertensive, and cardio-protective effects of five food-derived bioactive compounds: resveratrol, quercetin, coenzyme Q10, DHA and EPA and their proposed mechanisms of action are reviewed in detail.

Impact of oats in the prevention/management of hypertension.

Oats are a rich source of a soluble fibre, beta-glucan, phenolic compounds, as well as functional lipid and protein components that could potentially aid in preventing and managing hypertension. Processing techniques commonly used to manufacture oat based foods have been shown to improve its physiological efficacy. Hypertension is a common condition that is a risk factor for cardiovascular disease, a primary cause of mortality worldwide. Though exercise and pharmacological interventions are often used in the management of hypertension, diet is an incredibly important factor. One preclinical study and a handful of clinical studies have shown that oat components/products are effective in lowering blood pressure. However, research in this area is limited and more studies are needed to elucidate the anti-hypertensive potential of oats.

Effects of cyanidin 3-O-glucoside and hydrochlorothiazide on T-cell phenotypes and function in spontaneously hypertensive rats.

Immune system dysfunction may contribute to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). We examined the effects of the anthocyanin, cyanidin 3-O-glucoside (C3G), and the diuretic, hydrochlorothiazide (HCT), on T-cell function in SHR. Five-week-old male SHR and Wistar-Kyoto (WKY) rats received water (n = 8/SHR; n = 8/WKY), 10 mg kg-1 day-1 C3G (n = 8/SHR; n = 8/WKY), 10 mg kg-1 day-1 HCT (n = 8/SHR; n = 8/WKY), or 10 mg kg-1 day-1 C3G + 10 mg kg-1 day-1 HCT (n = 8/SHR; n = 8/WKY) by oral gavage for 15 weeks. Spleens were used to assess T-cell phenotypes via flow cytometry and concanavalin A stimulated ex vivo cytokine production (IL-2, IL-10, TNFα, IFNγ) using a cytometric bead array. SHR had lower proportions of helper T-cells (Th) that were T-regulatory, CD62Llo, CD62L- and CD25+ compared to WKY. C3G treated SHR had higher proportions of Th that were CD62Llo and CD62L-, while HCT treated rats had higher CD62Lhi and CD62Llo and lower CD62L- compared to SHR control. The proportion of T-regulatory and Th that were CD25+ were not affected by treatment in SHR. Stimulated splenocytes from SHR produced lower concentrations of cytokines compared to WKY. C3G treated SHR produced higher while HCT treated SHR produced lower TNFα and IFNγ concentrations compared to controls. Our findings suggest that C3G has positive effects, whereas HCT further suppresses T-cell function in SHR.

Cyanidin 3-O-glucoside prevents the development of maladaptive cardiac hypertrophy and diastolic heart dysfunction in 20-week-old spontaneously hypertensive rats.

The present study investigated the effects of cyanidin 3-O-glucoside (C3G) in cardiomyocytes (CM) and fibroblasts exposed to endothelin 1 (ET1), as well as in the spontaneously hypertensive rat (SHR) model, alone or in combination with hydrochlorothiazide (HCT). Adult rat CM and cardiac fibroblasts (CF) were pretreated with C3G and co-incubated with ET1 (10-7 M) for 24 hours. Five-week-old male SHR and their normotensive controls, Wistar-Kyoto rats (WKY), received one of 4 treatments via oral gavage daily for 15 weeks: (1) water (control); (2) C3G (10 mg per kg per day); (3) HCT (10 mg per kg per day); (4) C3G + HCT (10 mg per kg per day each). Blood pressure (BP) was measured at 1, 8 and 15 weeks. Echocardiography measurements were performed at 15 weeks. C3G prevented ET1-induced CM death and hypertrophy. Stimulating CF with ET1 did not induce their phenoconversion; nevertheless, C3G inhibited un-stimulated CF differentiation. HCT slowed the rise of systolic BP (SBP) in the SHR over time (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs HCT = 129 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs HCT = 168 ± 7.3 mmHg), but C3G had no effect on SBP (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs C3G = 126 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs C3G = 186 ± 7.3 mmHg). SHRs treated with C3G, HCT, and C3G + HCT had lower left ventricular mass and shorter isovolumetric relaxation time compared to control SHRs. C3G ameliorated cardiac hypertrophy and diastolic dysfunction in SHRs.

Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors improve prognosis in patients with post-myocardial infarction (MI) related cardiac dysfunction. Resveratrol is a polyphenol that has been reported to be beneficial in hypertension, ischemic heart disease, and cardiotoxicity in preclinical studies. Accordingly, we investigated the comparative and combinatorial efficacy of resveratrol and perindopril (ACE inhibitor) treatment on MI-related cardiac remodeling and contractile dysfunction. METHODS: Left anterior descending artery-ligated and sham-operated male Sprague-Dawley rats were gavaged with vehicle, resveratrol, perindopril, and combination of resveratrol+perindopril (2.5 mg/kg bodyweight/day) for 8 weeks (starting immediately after acute MI). Echocardiography was performed to assess cardiac structure and function at baseline and 8 weeks. RESULTS: At 8 weeks, vehicle-MI rats had a significantly lower left ventricular ejection fraction (LVEF) and increased LV dilatation compared to vehicle-sham rats. MI rats treated with resveratrol, perindopril and a combination of both had significantly improved LVEF and reduced LV dilatation. Vehicle-treated MI rats also had increased level of lipid peroxidation product- malondialdehyde (MDA), proinflammatory protein- tumor necrosis factor-alpha (TNF-α) and cardiac fibrosis marker- collagen and decreased enzymatic activity of superoxide dismutase and catalase compared to vehicle-sham rats. Resveratrol, perindopril and combination of both significantly prevented the /ed to determine systolic functional parameter increase in MDA, TNF-α and collagen and improved the activity of superoxide dismutase and catalase in MI rats compared to vehicle-MI rats. CONCLUSION: Treatment with resveratrol or perindopril was equivalent in significantly improving remodeling and attenuation of contractile dysfunction in MI rats. Combination treatment also attenuated the cardiac abnormalities. The improvement in cardiac abnormalities may partly be through reducing oxidative stress by preventing the decrease in the activity of superoxide dismutase and catalase, and decreasing cardiac inflammation and fibrosis.

Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes.

Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 µmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor γ, GW9662 (1 µmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor γ activation.

Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress.

The purpose of this study was to examine the efficacy of an aqueous wild blueberry extract and five wild blueberry polyphenol fractions on an in vitro model of heart disease. Adult rat cardiomyocytes were pretreated with extract and fractions, and then exposed to norepinephrine (NE). Cardiomyocyte hypertrophy, cell death, oxidative stress, apoptosis and cardiomyocyte contractile function as well as the activities of calpain, superoxide dismutase (SOD) and catalase (CAT) were measured in cardiomyocytes treated with and without NE and blueberry fraction (BF). Four of five blueberry fractions prevented cell death and cardiomyocyte hypertrophy induced by NE. Total phenolic fraction was used for all further analysis. The NE-induced increase in oxidative stress, nuclear condensation, calpain activity and lowering of SOD and CAT activities were prevented upon pretreatment with BF. Reduced contractile function was also significantly improved with BF pretreatment. Blueberry polyphenols prevent NE-induced adult cardiomyocyte hypertrophy and cell death. The protective effects of BF may be in part attributed to a reduction in calpain activity and oxidative stress.