Red raspberry (Rubus ideaus) supplementation mitigates the effects of a high-fat diet on brain and behavior in mice.

OBJECTIVES: Research has shown that berries may have the ability to reverse, reduce, or slow the progression of behavioral dysfunction associated with aging and neurodegenerative disease. In contrast, high-energy and high-fat diets (HFD) may result in behavioral deficits like those seen in aging animals. This research examined whether red raspberry (Rubus ideaus) mitigates the effects of HFD on mouse brain and behavior. METHODS: Eight-week-old mice consumed a HFD (60% calories from fat) or a control diet (CD) with and without 4% freeze-dried red raspberry (RB). Behavioral tests and biochemical assays of brain tissue and serum were conducted. RESULTS: After 12 weeks on the diets, mice fed CD and HFD had impaired novel object recognition, but mice on the RB-supplemented diets did not. After approximately 20 weeks on the diets, mice fed HFD + RB had shorter latencies to find the escape hole in the Barnes maze than the HFD-fed mice. Interleukin (IL)-6 was significantly elevated in the cortex of mice fed HFD; while mice fed the CD, CD + RB, and HFD + RB did not show a similar elevation. There was also evidence of increased brain-derived neurotrophic factor (BDNF) in the brains of mice fed RB diets. This reduction in IL-6 and increase in BDNF may contribute to the preservation of learning and memory in HFD + RB mice. CONCLUSION: This study demonstrates that RB may protect against the effects HFD has on brain and behavior; however, further research with human subjects is needed to confirm these benefits.

Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high-fat diet.

OBJECTIVES: Consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. Blueberries may prevent and even reverse age-related alterations in neurochemistry and behavior. It was previously demonstrated that middle-aged mice fed HFD had impaired memory; however, supplementation of HFD with blueberry reduced these memory deficits. As a follow-up to that study, the brain tissue from HFD-fed mice with and without blueberry supplementation was assessed to determine the neuroprotective mechanism(s) by which blueberry allayed cognitive dysfunction associated with HFD. METHODS: Mice were fed HFDs (60% calories from fat) or low-fat diets (LFD) with and without 4% blueberry (freeze-dried, U.S. Highbush Blueberry Council). Microglia activation was assessed ex vivo and in vitro. The hippocampus was assessed for brain-derived neurotrophic factor (BDNF) and neurogenesis by measuring doublecortin (DCX). RESULTS: There was significantly less microglia ionized calcium binding adaptor molecule 1 staining and fewer microglia in the brains of mice fed HFD + blueberry compared to mice fed LFD and HFD. BV-2 microglial cells treated with serum collected from the mice fed the diets supplemented with blueberry produced less nitric oxide compared to cells treated with serum from mice fed HFD. BDNF levels were higher and the number of DCX-positive cells was greater in the hippocampus of mice fed HFD + blueberry compared to mice fed HFD. DISCUSSION: This study demonstrated that supplementation of a HFD with blueberry reduced indices of microglia activation and increased neuroplasticity, and these changes may underlie the protection against memory deficits in HFD-fed mice supplemented with blueberry.

Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

OBJECTIVE: Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. METHODS: Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. RESULTS: Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. DISCUSSION: In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells.

OBJECTIVES: The present study was carried out to determine if lyophilized açaí fruit pulp (genus, Euterpe), rich in polyphenols and other bioactive antioxidant and anti-inflammatory phytochemicals, is efficacious in reversing age-related cognitive deficits in aged rats. METHODS: The diets of 19-month-old Fischer 344 rats were supplemented for 8 weeks with 2% Euterpe oleracea (EO), Euterpe precatoria (EP), or a control diet. Rats were tested in the Morris water maze and then blood serum from the rats was used to assess inflammatory responses of BV-2 microglial cells. RESULTS: After 8 weeks of dietary supplementation with 2% EO or EP, rats demonstrated improved working memory in the Morris water maze, relative to controls; however, only the EO diet improved reference memory. BV-2 microglial cells treated with blood serum collected from EO-fed rats produced less nitric oxide (NO) than control-fed rats. Serum from both EO- and EP-fed rats reduced tumor necrosis factor-alpha (TNF-α). There is a relationship between performance in the water maze and the production of NO and TNF-α by serum-treated BV-2 cells, such that serum from rats with better performance was more protective against inflammatory signaling. DISCUSSION: Protection of memory during aging by supplementation of lyophilized açaí fruit pulp added to the diet may result from its ability to influence antioxidant and anti-inflammatory signaling.

The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing.

Previously, it has been shown that strawberry (SB) or blueberry (BB) supplementations, when fed to rats from 19 to 21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenols, including decreased stress signalling, increased neurogenesis, and increased signals involved in learning and memory. Thus, the present study was carried out to examine these mechanisms in aged animals by administering a control, 2 % SB- or 2 % BB-supplemented diet to aged Fischer 344 rats for 8 weeks to ascertain their effectiveness in reversing age-related deficits in behavioural and neuronal function. The results showed that rats consuming the berry diets exhibited enhanced motor performance and improved cognition, specifically working memory. In addition, the rats supplemented with BB and SB diets showed increased hippocampal neurogenesis and expression of insulin-like growth factor 1, although the improvements in working memory performance could not solely be explained by these increases. The diverse polyphenolics in these berry fruits may have additional mechanisms of action that could account for their relative differences in efficacy.

Stress-induced increases in depression-like and cocaine place-conditioned behaviors are reversed by disruption of memories during reconsolidation.

Maladaptive behavioral responses characteristic of post-traumatic stress disorders are notably resistant to treatment. We hypothesized that the pharmacological disruption of memories activated during reconsolidation might reverse established stress-induced increases in depression-like behaviors and cocaine reward. C57BL/6J mice were subjected to repeated social defeat stress (SDS), and examined for time spent immobile in a subsequent forced swim test (FST). An additional set of SDS-exposed mice were place-conditioned with cocaine, and tested for cocaine-conditioned place preference (CPP). All stress-exposed mice were then subjected to a single additional trial of SDS while under the influence of propranolol or cycloheximide to disrupt memory reconsolidation, then given one additional FST or CPP test the next day. Mice subjected to repeated SDS subsequently demonstrated increases in time spent immobile in the FST or in the cocaine-paired chamber. Vehicle-treatment followed by additional SDS exposure did not alter these behaviors, but propranolol or cycloheximide treatment reversed each of the potentiated responses in a dose-dependent manner. Overall, these results demonstrate that while repeated exposure to a social defeat stressor subsequently increased depression-like behavior and cocaine-CPP, disruption of traumatic memories made labile by re-exposure to SDS during reconsolidation may have therapeutic value in the treatment of established post-traumatic stress disorder-related behaviors.

A scoping review of training and deployment policies for human resources for health for maternal, newborn, and child health in rural Africa.

BACKGROUND: Most African countries are facing a human resources for health (HRH) crisis, lacking the required workforce to deliver basic health care, including care for mothers and children. This is especially acute in rural areas and has limited countries' abilities to meet maternal, newborn, and child health (MNCH) targets outlined by Millennium Development Goals 4 and 5. To address the HRH challenges, evidence-based deployment and training policies are required. However, the resources available to country-level policy makers to create such policies are limited. To inform future HRH planning, a scoping review was conducted to identify the type, extent, and quality of evidence that exists on HRH policies for rural MNCH in Africa. METHODS: Fourteen electronic health and health education databases were searched for peer-reviewed papers specific to training and deployment policies for doctors, nurses, and midwives for rural MNCH in African countries with English, Portuguese, or French as official languages. Non-peer reviewed literature and policy documents were also identified through systematic searches of selected international organizations and government websites. Documents were included based on pre-determined criteria. RESULTS: There was an overall paucity of information on training and deployment policies for HRH for MNCH in rural Africa; 37 articles met the inclusion criteria. Of these, the majority of primary research studies employed a variety of qualitative and quantitative methods. Doctors, nurses, and midwives were equally represented in the selected policy literature. Policies focusing exclusively on training or deployment were limited; most documents focused on both training and deployment or were broader with embedded implications for the management of HRH or MNCH. Relevant government websites varied in functionality and in the availability of policy documents. CONCLUSIONS: The lack of available documentation and an apparent bias towards HRH research in developed areas suggest a need for strengthened capacity for HRH policy research in Africa. This will result in enhanced potential for evidence uptake into policy. Enhanced alignment between policy-makers' information needs and the independent research agenda could further assist knowledge development and uptake. The results of this scoping review informed an in-depth analysis of relevant policies in a sub-set of African countries.

Inhibition of Gßγ-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward.

Inhibition of Gßγ-subunit signaling to phospholipase C ß3 has been shown to potentiate morphine-mediated antinociception while attenuating the development of tolerance and dependence in mice. The objective of this study was to determine the effect of Gßγ-subunit inhibition on antinociception and other pharmacological effects, such as respiratory depression, constipation, and hyperlocomotion, mediated by the µ-opioid receptor. The Gßγ-subunit inhibitor, gallein, was administered to C57BL/6J mice by intraperitoneal injection before morphine, and data were compared with mice treated with vehicle, morphine, or gallein alone. Morphine-induced antinociception was measured using the 55°C warm-water tail-withdrawal test. Pretreatment with gallein produced a dose-dependent potentiation of morphine-mediated antinociception, producing up to a 10-fold leftward shift in the morphine dose-response curve and extending the duration of antinociception induced by a single dose of morphine. Gallein pretreatment also prevented acute antinociceptive tolerance induced by morphine. In contrast, the dose-dependent respiratory depression and hyperlocomotion induced by morphine were not potentiated by gallein pretreatment. Similarly, gallein pretreatment did not potentiate morphine-conditioned place preference responses or morphine-induced constipation, as measured as a reduction in excreta. These results suggest that selectively inhibiting Gßγ-mediated signaling may selectively increase µ-opioid receptor-mediated antinociception without matching increases in adverse physiological effects.

The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells.

UNLABELLED: Previous research from our lab has demonstrated that dietary walnut supplementation protects against age-related cognitive declines in rats; however, the cellular mechanisms by which walnuts and polyunsaturated fatty acids (PUFAs) may affect neuronal health and functioning in aging are undetermined. OBJECTIVES: We assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs would protect cells against dopamine- and lipopolysaccharide-mediated cell death and calcium dysregulation. METHODS: Rat primary hippocampal neurons were pretreated with varying concentrations of walnut extract, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid prior to exposure to either dopamine or lipopolysaccharide. Viability was assessed using the Live/Dead Cellular Viability/Cytotoxicity Kit. Also, the ability of the cells to return to baseline calcium levels after depolarization was measured with fluorescent imaging. RESULTS: Results indicated that walnut extract, alpha-linolenic acid, and docosahexaenoic acid provided significant protection against cell death and calcium dysregulation; the effects were pretreatment concentration dependent and stressor dependent. Linoleic acid and eicosapentaenoic acid were not as effective at protecting hippocampal cells from these insults. DISCUSSION: Walnut extract and omega-3 fatty acids may protect against age-related cellular dysfunction, but not all PUFAs are equivalent in their beneficial effects.

Endogenous kappa opioid activation mediates stress-induced deficits in learning and memory.

We hypothesized that mice subjected to prolonged stress would demonstrate decreased performance in a learning and memory task attributable to the endogenous activation of the kappa opioid receptor (KOR). C57BL/6J mice were tested using the novel object recognition (NOR) assay at various time points after exposure to repeated forced swim stress (FSS). Unstressed mice demonstrated recognition of the novel object at the end of a procedure using three 10-min object interaction phases, with a recognition index (RI) for the novel object of 71.7+/-3.4%. However, 1 h after exposure to FSS, vehicle-pretreated mice displayed a significant deficit in performance (RI=58.2+/-4.1%) compared with unstressed animals. NOR was still significantly reduced 4 but not 24 h after FSS. Treatment with the KOR-selective antagonist norbinaltorphimine (10 mg/kg, i.p.) prevented the decline in learning and memory performance. Moreover, direct activation of the KOR induced performance deficits in NOR, as exogenous administration of the KOR agonist U50,488 [(+/-)-trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide] (0.3 mg/kg, i.p.) suppressed NOR (RI=56.0+/-3.9%). The effect of FSS on NOR performance was further examined in mice lacking the gene for the endogenous KOR agonist dynorphin (Dyn). Dyn gene-disrupted mice exposed to FSS did not show the subsequent learning and memory deficits (RI=66.8+/-3.8%) demonstrated by their wild-type littermates (RI=49.7+/-2.9%). Overall, these results suggest that stress-induced activation of the KOR may be both necessary and sufficient to produce subsequent deficits in novel object recognition.

Walnut-Associated Fatty Acids Inhibit LPS-Induced Activation of BV-2 Microglia.

Walnuts have high levels of the omega-3 fatty acid alpha-linolenic acid (C18:3n-3, ALA) and the omega-6 fatty acid linoleic acid (C18:2n-6, LA). Previous research has demonstrated that pre-treatment of BV-2 microglia with walnut extract inhibited lipopolysaccharide (LPS)-induced activation of microglia. As an extension of that study, the effects of walnut-associated fatty acids on BV-2 microglia were assessed. BV-2 murine microglia cells were treated with LA, ALA, or a combination of LA+ALA prior to or after exposure to LPS. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured in cell-conditioned media. Cyclooxeganse-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed in BV-2 microglia. Both LA and ALA protected against LPS-induced increases in NO, iNOS, COX-2, and TNF-alpha when used before LPS exposure. When BV-2 microglia were treated with fatty acids after LPS, only COX-2 and TNF-alpha were significantly attenuated by the fatty acids. There was no synergism of LA+ALA, as the LA+ALA combination was no more effective than LA or ALA alone. Fatty acids, like those found in walnuts, may protect against production of cytotoxic intermediates and cell-signaling molecules from microglia and may prove beneficial for preventing age- or disease-related neurodegeneration.

Blueberries Improve Neuroinflammation and Cognition differentially Depending on Individual Cognitive baseline Status.

Daily supplementation of blueberries (BBs) reverses age-related deficits in behavior in aged rats. However, it is unknown whether BB is more beneficial to one subset of the population dependent on baseline cognitive performance and inflammatory status. To examine the effect of individual differences on the efficacy of BB, aged rats (17 months old) were assessed for cognition in the radial arm water maze (RAWM) and divided into good, average, and poor performers based on navigation errors. Half of the rats in each cognitive group were then fed a control or a 2% BB diet for 8 weeks before retesting. Serum samples were collected, pre-diet and post-diet, to assess inflammation. Latency in the radial arm water maze was significantly reduced in the BB-fed poor performers (p < .05) and preserved in the BB-fed good performers. The control-fed good performers committed more working and reference memory errors in the post-test than pretest (p < .05), whereas the BB-fed good performers showed no change. An in vitro study using the serum showed that BB supplementation attenuated lipopolysaccharide (LPS)-induced nitrite and tumor necrosis factor-alpha, and cognitive performance was associated with innate anti-inflammatory capability. Therefore, consumption of BB may reverse some age-related deficits in cognition, as well as preserve function among those with intact cognitive ability.

Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus.

Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study, we investigated whether polyphenols in blueberries can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1beta and TNF-alpha, the neurotrophic factor IGF-1, and the transcription factor NF-kappaB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1beta, TNF-alpha, and NF-kappaB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions, perhaps via alteration of gene expression.

Protective Effects of Foods Containing Flavonoids on Age-Related Cognitive Decline.

PURPOSE OF REVIEW: Evidence suggests that flavonoids, polyphenolic compounds found in many plant-derived foods, such as berries, may allay cognitive impairment. We review recent research exploring the protective effects of flavonoids on age-related cognitive decline and neurodegenerative disorders in humans and animals. We also address the mechanisms by which flavonoids may exert their effects and promising avenues of future research. RECENT FINDINGS: Flavonoids have been found to decrease neuroinflammation, reduce oxidative stress, and mediate neuroplasticity in animal models of neurodegeneration and aging. Injecting flavonoids encased in metal nanoparticles may further enhance the efficacy of flavonoids. Animal studies also demonstrate that flavonoid supplementation may alleviate neurodegenerative cognitive and memory impairments. Limited human studies, however, demonstrate the need for further clinical research investigating flavonoids. Flavonoid supplementation, as well as dietary modification to include whole foods high in flavonoids, may provide therapeutic potential for aging individuals experiencing cognitive deficits resulting from neurodegeneration.

Mitigating the effects of high fat diet on the brain and behavior with berry supplementation.

Research on the potential of berries to modulate the effects of high fat diets on the brain and behavior is a relatively small and growing field. This review provides an overview of current findings from animal studies assessing the impact of high fat diets supplemented with blueberries, blackberries, grapes and jaboticaba berries on cognitive performance and neuroprotection. High fat diets are demonstrated to increase brain markers of oxidative stress and inflammation and result in other neural alterations that can contribute to impairments in learning and memory. Berries are rich in bioactive polyphenols and show promise for mitigating the effects of high fat diet. Challenges to systematic research include variability in diet composition and regimens, limitations of predominantly male animal models, and other factors. Links between peripheral inflammation and CNS dysfunction have implications for the understanding of underlying mechanisms and directions for future research.

Effects of Concord grape juice on cognitive and motor deficits in aging.

OBJECTIVE: Animals and humans show increased motor and cognitive declines with aging that are thought to be due to increased susceptibility to the long-term effects of oxidative stress and inflammation. Previous findings have suggested that reversals in these age-related declines might be accomplished by increasing the dietary intake of polyphenolics found in fruits and vegetables, especially those identified as being high in antioxidant and anti-inflammatory activities. METHODS: We investigated the beneficial effects of two concentrations of Concord grape juice (10% and 50%) compared with a calorically matched placebo for their effectiveness in reversing age-related deficits in behavioral and neuronal functions in aged Fischer 344 rats. RESULTS: Rats that drank the 10% grape juice from age 19 to 21 mo had improvements in oxotremorine enhancement of K+-evoked release of dopamine from striatal slices and in cognitive performance on the Morris water maze, and the 50% grape juice produced improvements in motor function. CONCLUSIONS: These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, polyphenolics in foods may be beneficial in reversing the course of neuronal and behavioral aging, possibly through a multiplicity of direct and indirect effects that can affect a variety of neuronal parameters.

The M3 muscarinic receptor i3 domain confers oxidative stress protection on calcium regulation in transfected COS-7 cells.

Evidence suggests that muscarinic receptors (MAChRs) are involved in various aspects of neuronal and vascular functioning, and that there is selective oxidative stress sensitivity (OSS) among MAChR subtypes. COS-7 cells transfected with M1, M2 and M4 subtypes show greater OSS than the M1 and M3 subtypes, as seen by the decreased ability of cells to extrude or sequester calcium (Ca(2+)) following exposure to dopamine (DA) or A beta 25-35, and depolarization by oxotremorine. We sought to determine which receptor domain may be responsible for the differential vulnerability to OS between 'OS-sensitive' (M1) and 'non-sensitive' (M3) subtypes. Comparison of the amino acid sequences of each receptor has shown that the third cytoplasmic loop (i3 loop) is the domain with the most variability between the two subtypes. Therefore, mutations were made by either deleting or exchanging the i3 loop of M1 and M3 receptors. Experiments revealed that deletions of the i3 loop increased DA sensitivity (a lower percentage of cells showing recovery of [Ca(2+)](i) following depolarization) in both receptors. Chimerics of M1 in which the i3 loop of the M3 was exchanged with the i3 loop of the M1 (M1M3i3) showed that DA sensitivity was reduced (a greater percentage of cells showing increases in calcium clearance) following depolarization. The M3 chimerics containing the M1 i3 loop (M3M1i3) offered no protection against DA-induced decrements in calcium buffering. Results suggest that the longer i3 loop of the M3 may decrease OSS, possibly playing a role in targeting antioxidants to specific receptor sites that impart OSS.

Effect of diet on the disruption of operant responding at different ages following exposure to (56)Fe particles.

Rats were exposed to 2.0 Gy of (56)Fe particles to study the relationship between age and diet in the heavy particle-induced disruption of performance on an ascending fixed-ratio task. Irradiation produced a disruption of operant responding in rats tested 5 and 8 months after exposure, which was prevented by maintaining the rats on a diet containing strawberry, but not blueberry, extract. When tested 13 and 18 months after irradiation there were no differences in performance between the radiated rats maintained on control, strawberry or blueberry diets. These observations suggest that the beneficial effects of antioxidant diets may be dependent upon the age of testing.

Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress.

Dietary supplementation with fruit or vegetable extracts can ameliorate age-related declines in measures of learning, memory, motor performance, and neuronal signal transduction in a rat model. To date, blueberries have proved most effective at improving measures of motor performance, spatial learning and memory, and neuronal functioning in old rats. In an effort to further characterize the bioactive properties of fruits rich in color and correspondingly high in anthocyanins and other polyphenolics, 19-month-old male Fischer rats were fed a well-balanced control diet, or the diet supplemented with 2% extract from either blueberry, cranberry, blackcurrant, or Boysenberry fruit for eight weeks before testing began. The blackcurrant and cranberry diets enhanced neuronal signal transduction as measured by striatal dopamine release, while the blueberry and cranberry diets were effective in ameliorating deficits in motor performance and hippocampal HSP70 neuroprotection; these changes in HSP70 were positively correlated with performance on the inclined screen. It appears that the polyphenols in blueberries and cranberries have the ability to improve muscle tone, strength and balance in aging rats, whereas polyphenols in blueberries, cranberries and blackcurrants have the ability to enhance neuronal functioning and restore the brain's ability to generate a neuroprotective response to stress.

Exposure to HIV-1 Tat in brain impairs sensorimotor gating and activates microglia in limbic and extralimbic brain regions of male mice.

Human immunodeficiency virus (HIV) infection is associated with mood disorders and behavioral disinhibition. Impairments in sensorimotor gating and associated neurocognitive disorders are reported, but the HIV-proteins and mechanisms involved are not known. The regulatory HIV-1 protein, Tat, is neurotoxic and its expression in animal models increases anxiety-like behavior concurrent with neuroinflammation and structural changes in limbic and extra-limbic brain regions. We hypothesized that conditional expression of HIV-1 Tat1-86 in the GT-tg bigenic mouse model would impair sensorimotor gating and increase microglial reactivity in limbic and extralimbic brain regions. Conditional Tat induction via doxycycline (Dox) treatment (0-125 mg/kg, i.p., for 1-14 days) significantly potentiated the acoustic startle reflex (ASR) of GT-tg mice and impaired prepulse inhibition (PPI) of this response in a dose-dependent manner when Dox (100mg/kg) was administered for brief (1 day) or prolonged (daily for 7 days) intervals. A greater proportion of active/reactive Iba1-labeled microglia was seen in the anterior cingulate cortex (ACC), dentate gyrus, and nucleus accumbens core when Tat protein was induced under either brief or prolonged expression conditions. Other subregions of the medial prefrontal cortex, amygdala, hippocampal formation, ventral tegmental area, and ventral pallidum also displayed Tat-induced microglial activation, but only the activation observed in the ACC recapitulated the pattern of ASR and PPI behaviors. Tat exposure also increased frontal cortex GFAP. Pretreatment with indomethacin attenuated the behavioral effects of brief (but not prolonged) Tat-exposure. Overall, exposure to HIV-1 Tat protein induced sensorimotor deficits associated with acute and persistent neuroinflammation in limbic/extralimbic brain regions.