Hazelnut modulates neurobehaviour and ameliorates ageing-induced oxidative stress, and caspase-3-mediated apoptosis in mice

2020 ◽  
Vol 13 ◽  
Author(s):  
Anthony Tope Olofinnade ◽  
Adejoke Yetunde Onaolapo ◽  
Olakunle James Onaolapo ◽  
Olugbenga Adekunle Olowe

Background: Organismal aging has been associated with deleterious effects in different body tissues and organs, including the brain. There have been reports from ancient medicinal scripts of the beneficial effects of nuts like hazelnut in preventing aging induced-brain atrophy and memory loss. Objectives: This study examined the potential beneficial effects of a diet supplemented with two different (Italian and Turkish) cultivars of hazelnut on the brain of aged mice. Methods: Aged (24 months old) mice were randomly assigned into 7 groups of ten mice each. Mice were grouped as standard diet (SD) control, three groups of Turkish and three groups of Italian hazelnut incorporated into SD at 2, 4 and 8% respectively. Animals were fed standard or hazelnut diet for 8 weeks. On day 56, behaviours in the elevated plus maze, radial-arm maze, open field, and Y-maze paradigms were monitored and scored, following which animals were euthanized. The brains were removed, weighed and homogenized for the assessment of specific biochemical tests. Result: Results showed that hazelnut-supplemented diet was associated with significantly increased weight gain, with the Italian hazelnut being associated with greater weight gain. Hazelnut-supplemented diet also increased behavioural parameters such as horizontal locomotion and grooming, while it decreased rearing activity. Working-memory also improved significantly with both cultivars of hazelnut, while anxiety indices were reduced at lower concentrations of Italian, and higher concentrations of Turkish hazelnut. Both hazelnut varieties were associated with reduction in acetylcholinesterase activity, reduction in superoxide dismutase activity, reduction in nitric oxide levels, reduction in caspase-3 level, but increased dopamine level. Conclusion: Overall hazelnut cultivars have beneficial effects on the brain in aged mice; suggesting a possible role in the prevention or management of age-related neurodegenerative changes.

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Michal Jandzinski ◽  
Venugopal Venna ◽  
Anjali Chauhan ◽  
Joerg Graf ◽  
Louise D McCullough

Background: Circulating inflammatory markers increase with age. This pro-inflammatory milieu makes the organism less capable of coping with stressors such as stroke. Age related inflammation occurs in both the brain and peripheral tissues like the gastro-intestinal tract. There is increasing recognition that commensal bacteria in the GI tract are altered with age or with germ-free housing, affecting the brain. The change occurs most notably in the ratio of two major phyla of the microbiome, the Firmicutes and Bacteroidetes . Young age is associated with a low ratio of the two but this ratio increases with age, which has been linked to many diseases including obesity, hypertension, and diabetes which are major risk factors for stroke. Hypothesis: We hypothesized that there would be age-related differences in the microbiome, and that restoration of a young microbiome would improve functional recovery in aged mice. Methods: Fecal transplants from young and aged donors were administered to recipient animals after suppression of endogenous microbial compositions through concentrated Streptomycin. This allowed for successful colonization of the gut with the newly transplanted microbiome. A transient middle cerebral artery occlusion (MCAO) was used in young (3-4 month) and aged (18-20 month) male mice 4 weeks after transplant. Functional recovery was assessed by neurological deficit scores, the hang wire test, and open field activity. The Y-maze was used to assess cognitive impairment. Results: We successfully reversed the microbiomes of aged organisms and gave young animals “aged” biomes. Animals with “aged” microbiomes prior to stroke had worsened functional recovery based on all behavioral tests. The “aged” biome increased mortality rates most notably in the young recipients which had over 50% mortality. Aged mice had significantly improved functional recovery as assessed by the HW test ( P < 0.05 ) and NDS after reconstitution of “young” microbiome prior to stroke compared to aged control animals with the normal “aged” microbiomes. Conclusion: Aged mice have high Firmicutes and Bacteroidetes relative abundances. Manipulation of the microbiome in young and aged mice is possible. Restoration of a youthful biome improved functional recovery in aged mice.


2020 ◽  
Author(s):  
Maria Pilar Blasco ◽  
Anjali Chauhan ◽  
Pedram Honarpisheh ◽  
Hilda Ahnstedt ◽  
John d’Aigle ◽  
...  

Abstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation and mast cells residing in the gut are a primary source of histamine. Methods Stroke was induced in male C57BL/6J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice, mice underwent MCAO surgery and were euthanized at 6h, 24h and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice was associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. Results We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of mast cells and histamine receptors in the gut. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24 hours post-stroke. Conclusion An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome.


2021 ◽  
Vol 22 (21) ◽  
pp. 11859
Author(s):  
Elodie Passeri ◽  
Kamil Elkhoury ◽  
Maria Camila Jiménez Garavito ◽  
Frédéric Desor ◽  
Marion Huguet ◽  
...  

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (−50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1203-1203
Author(s):  
Gunter Eckert ◽  
Gunter Esselun ◽  
Elisabeth Koch ◽  
Nils Schebb

Abstract Objectives Neuroinflammation contributes to brain-aging which may be mitigated by anti-inflammatory oxylipins. Based on our previous findings that a 6% walnut-enriched diet alone, and additional physical activity (PA), enhanced cognition in 18 months old NMRI, we now investigated the effects of this diet on oxylipin- and inflammatory marker levels in liver and brain. Methods 18 months and 3 months old female NMRI mice were fed with a 6% walnut-enriched diet. Oxylipins were determined in brain and liver sections using LC-MS. Expression of IL1β gene was determined by qRT-PCR. Results The walnut diet compensates for the age related increase in IL1β gene expression in the liver of mice, whereas expression in the brain was not affected. Basal levels of oxylipins in brain and liver samples isolated from young mice were generally lower compared to aged mice. The walnut diet further increased oxylipin levels of walnut specific fatty acids in liver and brain of aged mice. Enrichment of linoleic acid (LA) and α-linolenic acid (ALA) derived oxylipin levels were quantitatively higher in the liver compared to the brain (P &lt; 0.0001). Hydroxy-oxylipins (HO) based on fatty acid LA were significantly increased in brain (P &lt; 0.001) and liver (P &lt; 0.0001) compared to control mice, while ALA based HO were only detected in the brains of walnut fed mice. The walnut diet in combination with physical activity (PA) reduced ARA based oxylipin levels (P &lt; 0.05). Across all groups, concentrations of prostanoids were higher in the brain as compared to liver (P &lt; 0.001). In the liver, walnuts tended to decrease PGD2 and TxB2 levels while increasing 6-keto PGF1α. The latter, as well as TxB2 tended to be decreased in the brain. Other ARA based prostanoids were unaffected. Effects of PA were contrary to each other, tending to increase ARA based prostanoids in the liver while decreasing them in the brain. PA further enhanced this effect in the brain, but tended to increase the inflammatory response in the liver. Conclusions A walnut diet differentially affects the oxylipin profile of liver and brain in aged mice. Production of oxylipins based on walnut fatty acids is generally increased. Attenuation of age-related, chronic inflammation in might be one of walnut's benefits and may contribute to a healthier aging of the brain. Funding Sources Research was supported by grants from California Walnut Commission.


Science ◽  
2020 ◽  
Vol 369 (6500) ◽  
pp. 167-173 ◽  
Author(s):  
Alana M. Horowitz ◽  
Xuelai Fan ◽  
Gregor Bieri ◽  
Lucas K. Smith ◽  
Cesar I. Sanchez-Diaz ◽  
...  

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)–specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.


2020 ◽  
Author(s):  
Maria Pilar Blasco ◽  
Anjali Chauhan ◽  
Pedram Honarpisheh ◽  
Hilda Ahnstedt ◽  
John d’Aigle ◽  
...  

Abstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation and mast cells residing in the gut are a primary source of histamine. Methods Stroke was induced in male C57BL/6J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice, mice underwent MCAO surgery and were euthanized at 6h, 24h and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice was associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. Results We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of mast cells and histamine receptors in the gut. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24 hours post-stroke. Conclusion An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome.


2021 ◽  
Vol 12 (1) ◽  
pp. 12
Author(s):  
Vasudevan Mani ◽  
Nur Syamimi Mohd Azahan ◽  
Kalavathy Ramasamy ◽  
Siong Meng Lim ◽  
Abu Bakar Abdul Majeed

Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), β-amyloid (Aβ1-40 and Aβ1-42), β-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Aβ1-40, and Aβ1-42, BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.


2020 ◽  
Author(s):  
Maria Pilar Blasco ◽  
Anjali Chauhan ◽  
Pedram Honarpisheh ◽  
Hilda Ahnstedt ◽  
John d’Aigle ◽  
...  

Abstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation and mast cells residing in the gut are a primary source of histamine. Methods Stroke was induced in male C57BL/6J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice, mice underwent MCAO surgery and were euthanized at 6h, 24h and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice was associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. Results We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of mast cells and histamine receptors in the gut. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24 hours post-stroke. Conclusion An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome.


2020 ◽  
Vol 237 (04) ◽  
pp. 446-449
Author(s):  
Irén Szalai ◽  
Fanni Pálya ◽  
Anita Csorba ◽  
Miklós Tóth ◽  
Gabor Mark Somfai

AbstractThere is only limited information available on the effects of physical exercise on the posterior pole. Retinal circulation is autoregulated similarly to the brain vasculature in order to provide constant flow and thus constant nutrition of the inner retinal structures while the choroid is mostly controlled by the sympathetic nervous system. The available data show that physical exercise may indeed have a positive effect on the retina and visual function. The assessment of retinal structure could serve as a marker in sports medicine, whereas physical activity could exert a positive protective effect against diseases such as diabetic retinopathy or age-related macular degeneration. According to our theory, similar to the term “trained heart” used in cardiology and sports medicine, the term “trained eye” could also be coined. This latter term would help to further emphasize the beneficial effects of physical exercise that works protectively not only for the cardiovascular but for the visual system as well, and thus could further help in the fight against avoidable blindness worldwide.


2017 ◽  
Vol 31 (11) ◽  
pp. 1419-1429 ◽  
Author(s):  
Stephen H Robertson ◽  
Erin B Rasmussen

Diet-induced obesity is a laboratory procedure in which nonhuman animals are chronically exposed to a high-fat, high-sugar diet (i.e. cafeteria diet), which results in weight gain, altered sensitivity to reward, and alterations in the dopamine D2 system. To date, few (if any) studies have examined age-related diet-induced obesity effects in a rat model or have used an impulsive choice task to characterize diet-induced behavioral alterations in reward processes. We exposed rats to a cafeteria-style diet for eight weeks starting at age 21 or 70 days. Following the diet exposures, the rats were tested on a delay discounting task – a measure of impulsive choice in which preference for smaller, immediate vs larger, delayed food reinforcers was assessed. Acute injections of haloperidol (0.03–0.3 mg/kg) were administered to assess the extent to which diet-induced changes in dopamine D2 influence impulsive food choice. Across both age groups, rats fed a cafeteria diet gained the most weight and consumed more calories than rats fed a standard diet, with rats exposed during development showing the highest weight gain. No age- or diet-related baseline differences in delay discounting were revealed, however, haloperidol unmasked subtle diet-related differences by dose-dependently reducing choice for the larger, later reinforcer. Rats fed a cafeteria diet showed a leftward shift in the dose-response curve, suggesting heightened sensitivity to haloperidol, regardless of age, compared to rats fed a standard diet. Results indicate that chronic exposure to a cafeteria diet resulted in changes in underlying dopamine D2 that manifested as greater impulsivity independent of age at diet exposure.


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