Aged Rat Brain Research Articles

Alteration of ADP-ribosylation in aging rat brain astrocytes

DNA damage and the enzyme poly (ADP-ribose) polymerase (PARP) associated with the pathogenesis of numerous age-related neurodegenerative disorders. Astrocytes play crucial roles in both support metabolic functions and cell viability of the brain. PARP regulates DNA damage and repair in the brain cells. In this study PARP activity and DNA strand break were investigated in the astrocytes isolated from young and aged rat brain. Three and 30-month-old rats were killed by decapitation and brains were removed onto an ice cooled glass plate. Astrocytes were isolated by sucrose density gradient centrifugation and glutamine synthetase (GS) served as a marker of the astrocytes lineage. The specific activity of PARP was assayed in permeabilized cells by measuring the incorporation of the ADPribose moiety of [3H]NAD into the nuclear acceptor proteins. The rate of DNA strand breaks was determined using a fluorescent dye and monitored spectrofluorimetry. An increase (about 75%) in the PARP activity was observed in the whole homogenates of aged rats, whereas this rise was more pronounced (about 360%) when the reaction was measured in the purified astrocyte preparations. The amount of DNA strand breaks was also higher in the astrocytes isolated from the aged brain as compared to that of young levels. The close relationship between the level of DNA strand breaks and PARP activity in the astrocytes suggest that these cells are susceptible to the metabolic alterations in aging. It is concluded that the astrocytes PARP might be considered as a therapeutic target for combating age related neurodegenerative disorders.

Cinnamaldehyde has beneficial effects against oxidative stress and nitric oxide metabolites in the brain of aged rats fed with long-term, high-fat diet

IntroductionIn this study, a novel use of Cinnamaldehyde in protection of brain oxidative stress was explored. MethodsMale Wistar rats were placed on either a high fat diet (HFD) or a normal diet, starting at 12 weeks of age and lasted for 16 weeks to establish metabolic syndrome. Then, Cinnamaldehyde (20 mg/kg) was daily given orally for 24 weeks. Malondialdehyde and nitric oxide metabolites (NOx) were evaluated in cerebellum, hippocampus, and cortex. ResultsThe HFD increased malondialdehyde in serum and the brain. Although, NOx concentration was increased in cerebellum, it decreased in serum and adrenal. Cinnamaldehyde lowered lipid peroxidation in serum and brain of HFD rats. Moreover, it restored NOx alterations in adrenal and cerebellum. ConclusionThe results of the present study provide evidence supporting beneficial effects of Cinnamaldehyde on brain disorders associated with metabolic syndrome and aging.

Glycomic and Proteomic Changes in Aging Brain Nigrostriatal Pathway

Parkinson's disease (PD) is a neurological disorder characterized by the progressive loss of functional dopaminergic neurons in the nigrostriatal pathway in the brain. Although current treatments provide only symptomatic relief, gene therapy has the potential to slow or halt the degeneration of nigrostriatal dopamine neurons in PD patients. Adeno-associated viruses (AAV) are vectors of choice in gene therapy because of their well-characterized safety and efficacy profiles; however, although gene therapy has been successful in preclinical models of the disease, clinical trials in humans have failed to demonstrate efficacy. Significantly, all primary AAV receptors of the virus are glycans. We thus hypothesize that age related changes in glycan receptors of heparan sulfate (HS) proteoglycans (receptor for rAAV2), and/or N-glycans with terminal galactose (receptor for rAAV9) results in poor adeno-associated virus binding in either the striatum or substantia nigra, or both, affecting transduction and gene delivery. To test our hypothesis we analyzed the striatum and substantia nigra for changes in HS, N-glycans and proteomic signatures in young versus aged rat brain striatum and substantia nigra. We observed different brain region-specific HS disaccharide profiles in aged compared with young adult rats for brain region-specific profiles in striatum versus substantia nigra. We observed brain region- and age-specific N-glycan compositional profiles with respect to the terminal galactose units that serve as receptors for AAV9. We also observed brain region-specific changes in protein expression in the aging nigrostriatal pathway. These studies provide insight into age- and brain region-specific changes in glycan receptors and proteome that will inform design of improved viral vectors for Parkinson Disease (PD) gene therapy.

Age-related change of GLP-1R expression in rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4

The glucagon-like peptide-1 receptor (GLP-1R) has been demonstrated as a potential therapeutic target for some neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. Besides, its distribution and density in brain regions are closely associated with cognition, motor function, learning and memory. Given the relationship between age and these neurological diseases, we firstly examined the influences of age on GLP-1R expression using [18F]AlF-NOTA-MAL-Cys39-exendin-4 microPET imaging. The image showed that GLP-1R expression in nearly all regions of the brain of aged rats was evidently lower than that of normal rats. Significant differences were found in olfactory, striatum, hypothalamus, substantial nigra, and hippocampus, which have inseparable relations with some mental and neurological diseases such as PD and AD. Data obtained from biodistribution and immunohistochemistry staining also confirmed the image results. Taken together, these results illustrated decreased expression of GLP-1R in the brain of aged rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4, which implied GLP-1R as a reliable target and GLP-1R PET imaging could be a promising technology in the field of neurological diseases.

Rapamycin Confers Neuroprotection Against Aging-Induced Oxidative Stress, Mitochondrial Dysfunction, and Neurodegeneration in Old Rats Through Activation of Autophagy.

Brain aging is an intricate and natural phenomenon exclusively characterized by oxidative stress, accumulation of oxidatively damaged macromolecules, and alterations in structure and function of neurons that further increase the risk factor for most of the neurodegenerative diseases. In addition, age-dependent defective autophagy has also been implicated to favor the pathogenesis and prevalence of the neurological diseases. Therefore, the development of strategies that delay aging and the concomitant neurological disorders remain elusive. Thus, the present study was undertaken to investigate the effect of rapamycin-induced activation of autophagy on aging-related oxidative stress, cell death, neuroinflammation, and neurodegeneration in rat brain. Our data demonstrated the significant age-related oxidative stress, apoptotic cell death, elevated inflammatory response, and reduced level of markers associated with rejuvenation and neural integrity, including the activities of ion channel transporters (Na+/K+-ATPase and Ca2+-ATPase) and acetylcholinesterase in the brain of old aged rats. Furthermore, rapamycin (0.5 mg/kg b.w. for 28 days) induced activation of autophagy provided significant protection to aging rat brain by reducing the aging-induced oxidative stress, apoptotic cell death, and markers of neurodegeneration. Thus, our data confirmed that autophagy plays a pivotal role in delaying brain aging plausibly by maintaining the cellular homeostasis, and structural and functional integrity of cells in the brain.

Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ.

Although reactive oxygen species mediated oxidative stress is a well-documented mechanism of aging, recent evidences indicate involvement of nitrosative stress in the same. As mitochondrial dysfunction is considered as one of the primary features of aging, the present study was designed to understand the involvement of nitrosative stress by studying the impact of a mitochondria-targeted antioxidant MitoQ, a peroxynitrite (ONOO-) scavenger, on mitochondrial functions. Four groups of rats were included in this study: Group I: Young-6months (-MitoQ), Group II: Aged-22months (- MitoQ), Group III: Young-6months (+ MitoQ), Group IV: Aged-22months (+ MitoQ). The rats belonging to group III and IV were treated with oral administration of MitoQ (500μM) daily through drinking water for 5weeks. MitoQ efficiently suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein bound 3-nitrotyrosine. MitoQ normalized enhanced caspase 3 and 9 activities in aged rat brains and efficiently reversed ONOO- mediated mitochondrial complex I and IV inhibition, restored mitochondrial ATP production and lowered mitochondrial membrane potential loss. To ascertain these findings, a mitochondrial in vitro model (iron/ascorbate) was used involving different free radical scavengers and anti-oxidants. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-L-arginine-methyl ester and superoxide dismutase establishing the predominancy of ONOO- in the process compared to •NO and O 2•- . These results clearly highlight the involvement of nitrosative stress in aging process with MitoQ having therapeutic potential to fight against ONOO- mediated aging deficits.

Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by d-galactose.

ObjectiveThe aim of this study was to evaluate the antiaging effect of Schisandra chinensis lignans (SCL) by analyzing the characteristics in the serum of d-galactose (d-gal)-induced rats.MethodsForty male Wistar rats were randomly divided into control group, d-gal model group, low-dose SCL group (50 mg/kg/d), medium-dose SCL group (100 mg/kg/d), and high-dose SCL group (200 mg/kg/d). A serum metabolomics analysis method based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry was carried out to study the characteristics of d-gal-induced aging rats and evaluate the antiaging effects of SCL, and multivariate statistical analysis was performed for pattern recognition and characteristic metabolites identification. The relative levels of p19, p53, and p21 genes in the brain tissue were measured by quantitative real-time polymerase chain reaction for investigating the underlying mechanism.ResultsMetabolomics analysis showed that 15 biomarkers were identified and 13 of them recovered to the normal levels after the administration of SCL. Based on the pathway analysis, the antiaging mechanisms of SCL might be involved in the following metabolic pathways: energy, amino acid, lipid, and phospholipid metabolism. Furthermore, SCL significantly inhibited the mRNA expression level of p19, p53, and p21 in the brain of aging rats induced by d-gal.ConclusionThese results suggest that SCL can delay rat aging induced by d-gal through multiple pathways.

Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

ObjectiveWhether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension.Materials and MethodsFive aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (Ktrans) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex in vivo. The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry.ResultsAs compared with WKY rats, the Ktrans values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min−1 vs. 0.084 ± 0.017 min−1, p < 0.001 for hippocampus; 0.302 ± 0.072 min−1 vs. 0.052 ± 0.047 min−1, p < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant.ConclusionBlood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.

Age-Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthase and Increased Oxidative Stress in the Rat Brain.

Adropin is a peptide highly expressed in the brain. Emerging evidence indicates that low plasma levels of adropin are closely associated with aging and endothelial dysfunction. We hypothesized that aging reduces adropin levels in the brain, which correlates with reduced endothelial nitric oxide synthase (eNOS) and increased oxidative stress associated with age-related endothelial dysfunction. Cortical brain tissue and plasma were collected from young (10-12 weeks old) and aged (18-20 months old) male Sprague-Dawley naïve rats. Using RT-qPCR, we quantified the mRNA levels of the energy homeostasis associated (Enho) gene encoding for adropin. Western blotting was utilized to measure adropin and markers of endothelial dysfunction and oxidative stress in the brain tissue. Levels of adropin in plasma were measured using an ELISA kit. Compared to young rats, both Enho mRNA and protein levels were dramatically reduced in the aged rat brain, which was accompanied by a significant reduction in plasma adropin levels in aged compared to young rats. Additionally, total and phosphorylated levels of endothelial nitric oxide synthase (eNOS) were significantly decreased in aged rat brains and were associated with dramatically increased gp91phox-containing NADPH oxidase (a major source of free radicals) and 4-hydroxynonenal (4-HNE), a lipid peroxidation marker. Brain levels of Akt and caveolin-1 were significantly reduced in aged rats compared with young animals. Collectively, these findings indicate that adropin levels negatively correlate with markers of endothelial dysfunction and oxidative injury, which raises the possibility that loss of brain adropin might play a role in the pathogenesis and development of aging-associated cerebrovascular dysfunction.

Effects of Withania somnifera on Cholinergic Signaling in the Cerebral Cortex and Memory Function in the Aging Rat Brain

Effects of Withania somnifera on Cholinergic Signaling in the Cerebral Cortex and Memory Function in the Aging Rat Brain

Effects of cerebrolysin on nerve growth factor system in the aging rat brain.

Background:Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia. However, the effects of CBL on cognition and brain neurotrophin system in normal aging remain obscure.Objective:The aim of the present study was to examine the age-related modifications of endogenous neurotrophin systems in the brain of male Wistar rats and the effects of CBL on learning and memory as well as the levels neurotrophins and their receptors.Methods:Old (23–24 months) and young (2–3 months) male Wistar rats were used for the study. A half of animals were subjected to CBL course (2.5 ml/kg, 20 i.p. injections). Behavior of rats was studied using the open field test and simple water maze training. The contents of NGF and BDNF were studied using enzyme-linked immunosorbent assay; the expression of neurotrophin receptors was estimated by Western-blot analysis.Results:CBL treatment did not affect general status, age-related weight changes, general locomotor activity as well as general brain histology. In a water maze task, a minor effect of CBL was observed in old rats at the start of training and no effect on memory retention was found. Aging induced a decrease in neurotrophin receptors TrkA, TrkB, and p75NTR in the neocortex. CBL counteracted effects of aging on neocortical TrkA and p75NTR receptors and decreased expression of proNGF without influencing overall NGF levels. BDNF system was not significantly affected by CBL.Conclusion:The pro-neuroplastic “antiaging” effects of CBL in the neocortex of old animals were generally related to the NGF rather than the BDNF system.

Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration

AimIn the present study, attempts have been made to evaluate the potential role of fisetin, a caloric restriction mimetic (CRM), for neuroprotection in D-galactose (D-gal) induced accelerated and natural aging models of rat. Main methodsFisetin was supplemented (15mg/kg b.w., orally) to young, D-gal induced aged (D-gal 500mg/kg b.w subcutaneously) and naturally aged rats for 6weeks. Standard protocols were employed to measure pro-oxidants, antioxidants and mitochondrial membrane potential in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuronal, aging as well as inflammatory marker genes. We have also evaluated apoptotic cell death and synaptosomal membrane-bound ion transporter activities in brain tissues. Key findingsOur data demonstrated that fisetin significantly decreased the level of pro-oxidants and increased the level of antioxidants. Furthermore, fisetin also ameliorated mitochondrial membrane depolarization, apoptotic cell death and impairments in the activities of synaptosomal membrane-bound ion transporters in aging rat brain. RT-PCR data revealed that fisetin up-regulated the expression of autophagy genes (Atg-3 and Beclin-1), sirtuin-1 and neuronal markers (NSE and Ngb), and down-regulated the expression of inflammatory (IL-1β and TNF-α) and Sirt-2 genes respectively in aging brain. SignificanceThe present study suggests that fisetin supplementation may provide neuroprotection against aging-induced oxidative stress, apoptotic cell death, neuro-inflammation, and neurodegeneration in rat brain.

Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.

트레드밀 운동이 노화쥐 뇌의 sirtuin-3 발현과 mitochondrial permeability transition pore에 미치는 영향

트레드밀 운동이 노화쥐 뇌의 sirtuin-3 발현과 mitochondrial permeability transition pore에 미치는 영향

Spreading depolarization remarkably exacerbates ischemia-induced tissue acidosis in the young and aged rat brain

Spreading depolarizations (SDs) occur spontaneously in the cerebral cortex of subarachnoid hemorrhage, stroke or traumatic brain injury patients. Accumulating evidence prove that SDs exacerbate focal ischemic injury by converting zones of the viable but non-functional ischemic penumbra to the core region beyond rescue. Yet the SD-related mechanisms to mediate neurodegeneration remain poorly understood. Here we show in the cerebral cortex of isoflurane-anesthetized, young and old laboratory rats, that SDs propagating under ischemic penumbra-like conditions decrease intra and- extracellular tissue pH transiently to levels, which have been recognized to cause tissue damage. Further, tissue pH after the passage of each spontaneous SD event remains acidic for over 10 minutes. Finally, the recovery from SD-related tissue acidosis is hampered further by age. We propose that accumulating acid load is an effective mechanism for SD to cause delayed cell death in the ischemic nervous tissue, particularly in the aged brain.

Memantine reduces the production of amyloid-β peptides through modulation of amyloid precursor protein trafficking

Memantine, an uncompetitive glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as medication for the treatment of Alzheimer's disease (AD). It has been reported that memantine reduces amyloid-β peptide (Aβ) levels in both neuronal cultures and in brains of animal models of AD. However, the underlying mechanism of these effects is unclear. Here we examined the effect of memantine on Aβ production. Memantine was administered to 9-month-old Tg2576 mice, a transgenic mouse model of AD, at 10 or 20mg/kg/day in drinking water for 1 month. Memantine significantly reduced the amounts of both CHAPS-soluble and CHAPS-insoluble Aβ in the brains of Tg2576 mice. Memantine at 10mg/kg/day for 1 month also reduced the levels of insoluble Aβ42 in the brains of aged F344 rats. Moreover, memantine reduced Aβ and sAPPβ levels in conditioned media from rat primary cortical cultures without affecting the enzymatic activities of α-secretase, β-secretase, or γ-secretase. Notably, in a cell-surface biotinylation assay, memantine increased the amount of amyloid precursor protein (APP) at the cell surface without changing the total amount of APP. Collectively, our results indicate that chronic treatment with memantine reduces the levels of Aβ both in AD models and in aged animals, and that memantine affects the endocytosis pathway of APP, which is required for β-secretase-mediated cleavage. This leads to a reduction in Aβ production. These results suggest that memantine reduces Aβ production and plaque deposition through the regulation of intracellular trafficking of APP.

Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats

While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22–24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in aged patients. Moreover, our data argue against the use of the measurement of plasma l-arginine/l-ornithine ratio to estimate arginase activity in aged patients.

Saponins from Panax japonicus attenuate age-related neuroinflammation via regulation of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways.

Neuroinflammation is recognized as an important pathogenic factor for aging and related cognitive disorders. Mitogen-activated protein kinase and nuclear factor kappa B signaling pathways may mediate neuroinflammation. Saponins from Panax japonicus are the most abundant and bioactive members in rhizomes of Panax japonicus, and show anti-inflammatory activity. However, it is not known whether saponin from Panax japonicus has an anti-inflammatory effect in the aging brain, and likewise its underlying mechanisms. Sprague-Dawley rats were divided into control groups (3-, 9-, 15-, and 24-month-old groups) and saponins from Panax japonicus-treated groups. Saponins from Panax japonicus-treated groups were orally administrated saponins from Panax japonicus at three doses of 10, 30, and 60 mg/kg once daily for 6 months until the rats were 24 months old. Immunohistochemical staining and western blot assay results demonstrated that many microglia were activated in 24-month-old rats compared with 3- and 9-month-old rats. Expression of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase increased. Each dose of saponins from Panax japonicus visibly suppressed microglial activation in the aging rat brain, and inhibited expression levels of the above factors. Each dose of saponins from Panax japonicus markedly diminished levels of nuclear factor kappa B, IκBα, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. These results confirm that saponins from Panax japonicus can mitigate neuroinflammation in the aging rat brain by inhibition of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways.

Modulatory Effects of Decalepis hamiltonii Extract and Its Compounds on the Antioxidant Status of the Aging Rat Brain.

Objective:The present study was aimed to investigate the neuroprotective effects of Decalepis hamiltonii (Dh) aqueous root extract and its compounds against age-related oxidative stress (OS) in the discrete regions of the rat brain.Materials and Methods:Male Wistar albino rats of 4- and 22-month-old were divided into control and six supplemented groups. The supplemented groups were orally administered with ellagic acid (EA), 4-hydroxyisophthalic acid (4-HIA), and Dh extract for 30 days.Results:Age-related decrease in antioxidant enzyme activities was noticed. The hippocampus was found to be more vulnerable to OS as seen by the elevation in the OS markers. Supplementation of the Dh extract, EA, and 4-HIA was found to be effective in up-regulating the antioxidant status. However, the extent of up-regulation was more evident in Dh supplemented animals.Conclusion:Our results suggest that Dh extract and its compounds exhibit neuroprotective effects against age-related OS and can be used as a dietary therapeutic intervention for the treatment of neurological disorders.

Selenium attenuates apoptosis, inflammation and oxidative stress in the blood and brain of aged rats with scopolamine-induced dementia.

A potent antioxidant, selenium might modulate dementia-induced progression of brain and blood oxidative and apoptotic injuries. The present study explores whether selenium protects against experimental dementia (scopolamine, SCOP)-induced brain, and blood oxidative stress, apoptosis levels, and cytokine production in rats. Thirty-two rats were equally divided into four groups. The first group was used as an untreated control. The second group was treated with SCOP to induce dementia. The third and fourth groups received 1.5mg/kg selenium (sodium selenite) and SCOP+selenium, respectively. Dementia was induced in the second and forth groups by intraperitoneal SCOP (1mg/kg) administration. Brain, plasma, and erythrocyte lipid peroxidation levels as well as plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the SCOP group though they were low in selenium treatments. Selenium and selenium+SCOP treatments increased the lowered glutathione peroxidase activity, reduced glutathione, vitamins A and E concentrations in the brain, erythrocytes and plasma of the SCOP group. Apoptotic value expressions as active caspase-3, procaspase-9, and PARP were also increased by SCOP, while they were decreased by selenium and selenium+SCOP treatments. In conclusion, selenium induced protective effects against experimental dementia-induced brain, and blood oxidative injuries and apoptosis through regulation of cytokine production, vitamin E, glutathione concentrations, and glutathione peroxidase activity.