Maria Joao Santos-Marques

Green tea averts age-dependent decline of hippocampal signaling systems related to antioxidant defenses and survival

We previously found that prolonged consumption of green tea (GT), a rich source of antioxidant polyphenols, protected proteins and lipids against oxidation and reduced lipofuscin deposition in the rat hippocampal formation as well as improving spatial memory during aging. In this work, we sought to investigate whether GT treatment could interfere with age-related changes in redox status and cellular signaling systems related to oxidative stress and survival in the same brain region. To address this issue, five male Wistar rats were fed with GT from 12 to 19 months of age and results were compared to those obtained from controls age 19 months (C-19 M). A third group of rats was evaluated at 12 months of age to provide baseline data. At completion of the specified time points, the glutathione levels and antioxidant enzyme activities, the activation of the transcription factors cyclic AMP response element-binding (CREB) and nuclear factor-kappaB (NF-kappaB, p50 and p65 subunits), and the levels of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2) were measured in hippocampal formations. GT-treated rats presented higher reduced and lower oxidized glutathione levels and displayed favorable alterations in antioxidant enzyme activities compared to C-19 M animals. In addition, GT increased CREB activation and the levels of BDNF and Bcl-2, but had no effect on activation of NF-kappaB subunits, relative to age-matched controls. We conclude that long-term GT ingestion improves antioxidant systems and activates CREB in the aging rat hippocampal formation, leading to neuroprotection mediated by downstream upregulation of BDNF and Bcl-2.

Red wine antioxidants protect hippocampal neurons against ethanol-induced damage: a biochemical, morphological and behavioral study.

Chronic ethanol consumption increases oxidative stress, which accounts for the striking neurological changes seen in this condition. Notwithstanding, there is well-documented evidence that polyphenols, present in grape skin and seeds, exhibit a strong antioxidant activity. As red wine is rich in polyphenols, the aim of the present work was to evaluate their putative protective effects on the hippocampal formation by applying biochemical, morphological and behavioral approaches. Six-month old male Wistar rats were fed with red wine (ethanol content adjusted to 20%) and the results were compared with those from ethanol-treated (20%) rats and pair-fed controls. Biochemical markers of oxidative stress (lipid peroxidation, glutathione levels and antioxidant enzyme activities) were assessed on hippocampal homogenates. Lipofuscin pigment, an end product of lipid peroxidation, was quantified in hippocampal cornu ammonis 1 and 3 (CA1 and CA3) pyramidal neurons using stereological methods. All animals were behaviorally tested on the Morris water maze in order to assess their spatial learning and memory skills. In red wine-treated rats, lipid peroxidation was the lowest while presenting the highest levels of reduced glutathione and an induction of antioxidant enzyme activities. Morphological findings revealed that, contrary to ethanol, red wine did not increase lipofuscin deposition in CA1 and CA3 pyramidal neurons. Besides, red wine-treated animals learned the water maze task at a higher rate than ethanol group and had better performance scores by the end of the training period and on a probe trial. Actually, no significant differences were found between pair-fed controls and red wine-treated rats in morphological and behavioral data. Thus, our findings demonstrate that chronic consumption of red wine, unlike the ethanol solution alone, does not lead to a decline in hippocampal-dependent spatial memory. This may be due to the ability of red wine polyphenols to improve the antioxidant status in the brain and to prevent free radical-induced neuronal damage.

Chronic green tea consumption prevents age-related changes in rat hippocampal formation

The hippocampal formation undergoes considerable structural and functional modifications during aging and oxidative stress emerges as a key player in the process. In the present study, we investigated whether prolonged consumption of green tea (GT), which contains large amounts of polyphenols, could interfere with age-related changes in this brain region using biochemical, morphological and behavioral approaches. Ten male Wistar rats aged 19 months were fed with GT since 12 months of age and results compared to those obtained from controls aged 19 months (C-19M). At 12 months of age, another group of rats was evaluated to provide baseline data. Oxidative stress markers (protein carbonyls and malondialdehyde) were quantified in hippocampal homogenates and stereological methods were applied to estimate the deposition of lipofuscin in hippocampal CA3 pyramidal neurons. Morris water maze was used to assess spatial learning and memory. Aging increased oxidative markers and lipofuscin accumulation and was associated with impaired memory acquisition. However, GT treatment protected proteins and lipids against oxidation and prevented the increase of lipofuscin deposition compared to age-matched controls. Furthermore, the spatial learning abilities of GT-treated rats were significantly improved when compared to those from C-19M group. Taken together, these findings confirm the neuroprotective ability of GT in the hippocampal formation probably due to the reduction of oxidative stress-related damage observed during aging.

Modulation of rat cerebellum oxidative status by prolonged red wine consumption

A number of studies support the view that wine polyphenols can reinforce the endogenous antioxidant system by reducing ethanol (EtOH)‐induced neuronal oxidative damage. Herein, we have investigated the effects of prolonged red wine (RW) consumption on several biomarkers of redox status in the cerebellum, a brain region highly vulnerable to the noxious effects of EtOH. Adult male Wistar rats were given RW with an EtOH concentration adjusted to 20% for 6 months, and the results were compared with those obtained in EtOH‐treated (20%) and pair‐fed control (PFC) animals. Malondialdehyde (MDA) and glutathione levels, and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione‐S‐transferase (GST) and selenium‐dependent glutathione peroxidase (Se‐GPX) were estimated in cerebellum homogenates. Chronic RW ingestion resulted in diminished MDA and reduced glutathione levels in cerebellar tissue. Moreover, RW‐treated rats had a significant decrease in SOD, GR and GST activities but presented an increase in the activity of Se‐GPX compared with animals from EtOH and PFC groups. In contrast, CAT activity was not altered by RW and EtOH intakes. Taken together, these findings show that prolonged consumption of RW markedly modifies cerebellum redox status probably due to its high content of polyphenols.