Aged Wistar Rats Research Articles

Effects of Oxytocin Administration on Oxidative Markers in the Temporal Lobe of Aged Rats

Considering the relevance of oxidative stress in aging and antioxidant properties of oxytocin, which we previously demonstrated, we studied the effects of intraperitoneal oxytocin administration (10 mg/kg body mass for 12 days) on enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and also on malonic dialdehyde (MDA) level in the brain temporal lobe of aged (2-year-old) Wistar rats. In these rats, oxytocin treatment provided a significantly lower SOD enzymatic activity, somewhat greater GPx activity, and significantly lower MDA concentration, when compared to the respective indices in aged control rats. It is concluded that, due to its antioxidant effect, oxytocin can be considered a candidate for the development of a new therapeutic modality in aging and in related neuropsychiatric disorders.

Sildenafil treatment of vascular dementia in aged rats

Backgroundand purpose: In this study, we employed a multiple microinfarction (MMI) based vascular dementia (VaD) model in aged rats and tested the therapeutic effects of Sildenafil, a phosphodiesterase type 5 inhibitor, on cognitive decline, white matter damage, autophagy and inflammatory response associated with VaD. MethodsMale, aged (16–18 months) Wistar rats were subjected to MMI (800 ± 100, 70–100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days. Four experimental groups were employed: Sham control, Sham + Sildenafil, MMI, and MMI + Sildenafil. A battery of cognitive tests were performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation and PCR assay. ResultsSildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats. Sildenafil treatment of aged MMI rats significantly increases axon and myelin density in the corpus callosum and white matter bundles in the striatum, increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum, and increases synaptic protein expression in the cortex and striatum compared to aged control MMI rats. In addition, Sildenafil treatment of MMI in aged rats significantly decreases Beclin1 expression and inflammatory factors Monocyte chemoattractant protein-1 and Interleukin-1β expression in brain. Sildenafil treatment in aged rats does not improve cognitive outcome compared to aged sham control rats. ConclusionsSildenafil treatment of MMI in aged rats significantly improves cognition and memory at 1 month after MMI. Sildenafil treatment increases axon and myelin density, increases Synaptophysin expression, decreases autophagic activity and exerts anti-inflammatory effects which in concert may contribute to cognitive improvement in aged rats subjected to MMI.

A morphological study and expression patterns of iron regulatory proteins in aging Wistar rats retina after iron overload

A morphological study and expression patterns of iron regulatory proteins in aging Wistar rats retina after iron overload

PO-014 The effects of HIIT on ROS-AMPK- PGC-1α pathway in skeletal muscle and VO2max of ageing Wistar rats.

Objective To observe the 16 weeks of HIIT intervention on SOD,ROS and its related factors AMPK and oxidation capacity PGC-1α expression and the influence of the VO2max and its change rule in the process of the natural aging rats, To explore the correlation between the expression of ROS, AMPK and PGC-1αand the change of VO2max; Furthermore, it provides a theoretical basis for HIIT to delay the reduction of aerobic capacity in skeletal muscle ageing.
 Methods 58 male wistar rats(age：32 weeks) were selected and randomly divided into quiet group (C) and HIIT intervention group (H). All rats were fed in the barrier environment. Each group of rats entered the animal laboratory for a week of adaptive feeding and exercise. VO2max was tested and observed every two weeks in each group. Rats of group C don't exercise, group H at a rate of 50%, 70% and 90% VO2max corresponding alternation of 50 min/day, 5 days/week, for 16 weeks of exercise intervention, and according to the VO2max test results the exercise intensity. Both groups of rats in the intervention of 8 weeks, 16 weeks after the end of the 24 hours of materials, stripping rats soleus, SOD and content of ROS was tested by multifunctional enzyme mark, using western blot test the expression of AMPK and PGC-1α. VO2max, SOD, ROS test results and AMPK, PGC-1α, and relative expression data were analyzed using SPSS for one way ANOVA.
 Results The cardiopulmonary endurance of rats in group C and group H showed a decreasing trend in group C and group H during HIIT intervention, but the decrease trend in group H was slower than that in group C. 2. During 16 weeks aging , SOD expression of group C in the process of rendering first rise after falling, and expressed in 8 weeks SOD content was significantly lower than base value (P < 0.05), 16 weeks group C SOD levels higher than the base state. After 16 weeks of intervention, the expression of SOD in group H was relatively flat in the first 8 weeks, and the trend was in 8-16 weeks, and was significantly lower than 8 weeks in 16 weeks (P < 0.05). 3.The ROS content was significantly higher than basic state in 8 weeks and 16 weeks in the intervention process (P<0.05), and the ROS content was significantly higher than 8 weeks (P<0.05) at 16 weeks. The ROS content of group C and group H was significantly higher than that in the group at 8 weeks (P < 0.05). 4.The AMPK content in group C was significantly lower than that of the basic value (P<0.05), and the AMPK content in group H was significantly higher than that in group C (P<0.05). 5.After the intervention of 16 weeks, the content of PGC-1α in group C and group H showed a decrease trend and significantly lower than the basic value (P<0.05), but the content of group H was significantly higher than that of group C (P<0.05). 6.The changes of AMPK, PGC-1α and cardiopulmonary endurance were the same in all groups during the intervention.
 Conclusions 1.16 weeks of HIIT can effectively delay the decrease of SOD content in the aging rats, thus inhibiting the accumulation of ROS in the body. 2.16 weeks of HIIT intervention can effectively delay the expression of VO2max and AMPK and PGC-1α in aging rats. 3.16 weeks HIIT may delay the decrease of AMPK-PGC1 protein expression by inhibiting the accumulation of skeletal muscle ROS in the aging rats, thus inhibiting the decrease of VO2max.

Evidence for changing nerve growth factor signalling mechanisms during development, maturation and ageing in the rat molar pulp

To examine rat molar pulp innervation and identify complex cellular signalling systems involving nerve growth factor (NGF) and its p75 receptors (NGFR) at different stages of development, maturation and ageing. Decalcified mandibular first molar mesial cusps from Wistar rats of ages 0day; 1, 2, 3, 4, 6, 9, 12 and 24weeks (n=5 per group) were sectioned (10μm) and incubated with antibodies for NGF, NGFR, calcitonin gene-related peptide (CGRP) and neurofilament. Nerve densities in worn and intact regions of 3- to 24-week-old rats were compared by anova, Bonferroni and t-tests. During odontogenesis, differences in NGF and NGFR expression were observed, with no evidence of nerve fibres, suggesting a signalling mechanism controlling cellular differentiation and dentine formation. Tooth wear in 4-week rats was associated with reduced NGF expression and significantly decreased CGRP axons within affected odontoblast regions. The underlying subodontoblasts started expressing NGF which continued until 9weeks. This may promote a significant increase in CGRP nerve density in affected regions. Nerve density in intact odontoblast regions increased gradually and reached significant levels in 12-week rats. Reduction in nerve densities within worn and intact regions of cusps was observed at 24weeks. Age-related changes and responses to tooth wear may be controlled by the NGF signalling mechanism, with roles in odontoblast/subodontoblast communication and control of sensory innervation at different stages of tooth development, maturation and ageing. Greater understanding of cellular and nerve regulation in the injured pulp may promote therapeutic strategies for pulp survival.

Leptin stimulates the release of pro-inflammatory cytokines in hypothalamic astrocyte cultures from adult and aged rats.

Leptin is an adipose tissue-derived hormone that acts on the hypothalamus in order to maintain energy homeostasis. However, leptin can also induce an inflammatory response. Increasing evidence has highlighted a critical role of astrocytes in the effects of leptin on the hypothalamus. In addition, astrocytes participate in neuroinflammation by producing and releasing a wide range of inflammatory mediators. In this study, we aimed to investigate the age-dependent effect of leptin on pro- and anti-inflammatory cytokines released by the hypothalamic astrocyte cultures obtained from newborn, adult, and aged Wistar rats. In hypothalamic astrocytes from newborn rats, leptin did not change the release of pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). On the other contrary, leptin increased the release of both TNF-α and IL-1β in astrocyte cultures from adult and aged animals. Regarding the anti-inflammatory cytokine interleukin 10 (IL-10), we did not observe any change in response to leptin. In conclusion, our data suggests a pro-inflammatory action of leptin on the hypothalamus during aging. This in turn may be related to the triggering of metabolic disorders, as both of these conditions are associated with neuroinflammation.

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5mg/kg, 2h apart) and aged (mean 20 months old) (2 × 5mg/kg, 2h apart) rats receivedMDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents' brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of adegenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy".

Acrolein-mediated neurotoxicity in growing Wistar male rats

Acrolein is an environmental and food contaminant widely produced by thermal processed organic compounds. It can be used as a biocide and is known to be generated endogenously by lipid peroxidation. This study was designed for evaluating acrolein toxicity in the context of GFAP, MBP, neurofilaments and histological examination of brain tissues and also hematological paremeters in pubertal male rats. 3–4 weeks aged Wistar male rats were exposed to 0.5, 1 and 2 mg/kg/day acrolein for 90 days. According to acrolein exposure results, slight changes observed in hematological parameters, however no significant differences were observed in GFAP and MBP. Unlikely, acrolein caused several histopathological changes in brain tissues as well as neurofilament accumulation. It may be concluded that acrolein might contribute to formation of neurodegenerative disorders.

Myotendinous junction plasticity in aged ovariectomized rats submitted to aquatic training.

The study aims to describe the tissue plasticity of MTJ through the morphological analysis of MTJ soleus in ovariectomized aged female Wistar rats submitted to aquatic training. Forty aged Wistar rats, 1 year and 2 months of age, were divided into four groups: sedentary (S), trained (T), ovariectomized (O), and trained/ovariectomized (OT). Employing the transmission electron microscopy, the ultrastructural and morphometric elements were revealed. In the S group, changes in morphological characteristics as a consequence of the aging process were seen, demonstrated by the conical shape of the muscle cell extremity, a large area with collagen deposit, and misalignment of sarcomeres in series. The T group presented ample adjustments when revealed the organization of MTJ, through the increase of the contact area and greater lengths of sarcoplasmatic invaginations and evaginations. The O group revealed extensive tissue disorganization with muscle atrophy, reduction of MTJ contact area, and consequently, changes in sarcoplasmatic invaginations and evaginations. The OT group demonstrated extensive remodeling with restructuring MTJ through the increase of tissue contact area, extensive organization, parallel arrangement, and increased length of sarcoplasmatic invaginations and evaginations. The distal sarcomeres presented higher lengths compared to the proximal sarcomeres in both the groups. We conclude that aquatic training was effective in the organization and structural remodeling of the myotendinous interface of ovariectomized aged rats. There was a greater area of contact, and consequently, greater resistance in the myotendinous interface promoting a lower predisposition to injuries.

Effects of Aging in the Striatum and Substantia Nigra of a Parkinson's Disease Animal Model.

Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological models, but due to the limitations of the animal models, particularly in aged animals, the results are difficult to interpret. In this work, we investigated neurodegeneration induced by rotenone, as a pharmacological model of Parkinson's disease, in both young and aged Wistar rats. We assessed animal mobility, tyrosine hydroxylase staining in the substantia nigra pars compacta (SNpc), and TdT-mediated dUTP-biotin nick end labeling-positive nuclei and reactive oxygen species production in the striatum. Interestingly, the mobility impairment, dopaminergic neuron loss, and elevated number of apoptotic nuclei in the striatum of aged control rats were similar to young rotenone-treated animals. Moreover, we observed many ultrastructural alterations, such as swollen mitochondria in the striatum, and massive lipofuscin deposits in the SNpc of the aged rotenone-treated animals. We conclude that the rotenone model can be employed to explore age-related alterations in the ontogeny that can increase vulnerability in the striatum and SNpc, which may contribute to Parkinson's disease pathogenesis.

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system.

Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats.

Oxytocin (OT) is a well-known neuropeptides which together with vasopressin, melatonin, insulin and other hormones can alter both behavior and physiological or neuronal functions. This growing interest on OT roles is also based on the demonstrated beneficial effects as a stress reliever and a social bonding agent. The association between old age and OT was only vaguely studied. Little or few is known on the effect of the OT hormone on the old body. Hereby, we present our preliminary results in the research on behavioral changes regarding the intraperitoneal administration of OT in aged rats. OT was administered for 8 days in Wistar aged rats in parallel with saline administration for control group. Behavioral markers were assessed in some specific behavioral tasks, such as the Y-Maze test for short-term working memory, Open Field test, Elevated Plus Maze, and Forced Swim test for anxious and depressive behavior assessment, and Three-chambered Maze test for sociability assessment. Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT). Similarly, significant differences were obtained regarding the social behavior of the intraperitoneal OT-treated animal as compared to control group, the animals showing increased sociability and social preference for the stranger animal in TCT. However, no significant effects on the working memory (assessed as spontaneous alternation in YMT) were observed. Intraperitoneal administration of OT in aged rats has clear effects on anxious and depressive behavior, but no significant effects on the working memory. Also, several beneficial effects of OT on social preferences and sociability were observed.

Modulation of miRNA expression in aged rat hippocampus by buttermilk and krill oil

The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rats following a 3-month supplementation. The combination of two phospholipidic concentrates of krill oil (KOC) and buttermilk (BMFC) origin modulated the hippocampal expression of 119 miRNAs (11 were common to both BMFC and BMFC + KOC groups). miR-191a-5p and miR-29a-3p changed significantly only in the BMFC group, whereas miR-195-3p and miR-148a-5p did so only in the combined-supplemented group. Thirty-eight, 58, and 72 differentially expressed genes (DEG) were found in the groups supplemented with KOC, BMFC and BMFC + KOC, respectively. Interaction analysis unveiled networks of selected miRNAs with their potential target genes. DEG found in the KOC and BMFC groups were mainly involved in neuroactive processes, whereas they were associated with lysosomes and mRNA surveillance pathways in the BMFC + KOC group. We also report a significant reduction in hippocampal ceramide levels with BMFC + KOC. Our results encourage additional in-depth investigations regarding the potential beneficial effects of these compounds.

Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity

S-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation. Furthermore, hypothalamic levels of pro-inflammatory markers decrease, meanwhile those of the anti-inflammatory cytokine IL-10 increases. Interestingly, peripheral NEFA decreases alike circulating leptin and resistin levels. These data demonstrate that hypothalamic s-resistin controls fuel mobilization and adipokines secretion. Importantly, central s-resistin downregulation improves systemic insulin sensitivity, as demonstrated after an IPGTT. Interestingly, our data also indicate that s-resistin downregulation could improve hypothalamic inflammation in aged Wistar rats. Altogether, our findings suggest that hypothalamic s-resistin seems to be a key regulator of the brain-fat axis which links inflammation with metabolic homeostasis.

Aerobic and strength training induce changes in oxidative stress parameters and elicit modifications of various cellular components in skeletal muscle of aged rats

Skeletal muscle aging is associated with loss of mass, function, and strength-a condition known as sarcopenia. It has been reported that sarcopenia can be attenuated by physical exercise. Therefore, we investigated whether 2 different physical exercise protocols could modulate and induce changes in oxidative and inflammatory parameters, as well as in BDNF and DNA repair enzyme levels in skeletal muscle tissue of aged rats. Aging Wistar rats performed treadmill or strength training for 50 min 3 to 4 times a week for 8 weeks. Strength training decreased 2′,7′-dichlorofluorescein (DCFH) oxidation (P = 0.0062); however, nitric oxide, protein deglycase DJ-1, and tumor necrosis factor alpha (TNF-α) levels increased after aerobic training (P = 0.04, P = 0.027 and P = 0.009, respectively). Both exercise protocols increased superoxide dismutase (SOD) and catalase (CAT) activity (P = 0.0017 and P = 0.0326) whereas the activity of glutathione (GSH) (P = 0.0001) was decreased. Brain-derived neurotropic factor (BDNF) levels were not affected by exercise, but 8-oxoguanine glycosylase (OGG1) decreased after strength training (P = 0.0007). In conclusion, oxidative parameters showed that skeletal muscle adapt to increased ROS levels, reducing the risk of free radical damage to the tissue after both exercise protocols. These results show that the effects of physical exercise on skeletal muscle are mediated in an exercise type-dependent manner.

Diabetic tubulopathy: effect of toll-like receptor 2, toll-like receptor 4, and nuclear factor κb in elderly type 2 diabetes mellitus patients

Objective The aims of the current study were to investigate the role of toll-like receptor (TLR)2, TLR4, and nuclear factor κB (NF-κB) expression in the pathogenesis of diabetic nephropathy (DN) in elderly type 2 diabetics, and also to determine the functional role of TLR2, TLR4, and NF-κB in tubular inflammation. Background Chronic kidney disease is one of the major complications of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. There is growing evidence indicating that chronic low-grade inflammatory response is a recognized factor in the pathogenesis and progression of diabetic renal injury. Patients and methods Our study included a human part and an animal part, in the human part, participants were divided into four groups; old patients: 30 T2DM patients aged 65 years and above with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy, old control: 20 age- matched and sex-matched healthy persons aged 65 years and above serving as a control group, young patients: 30 T2DM patients aged less than 65 years with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy and young control: 20 age-matched and sex-matched healthy persons aged less than 65 years serving as a control group. We took a full history of all patients and concluded complete physical examination. Mean arterial pressure, BMI and fundus examination were done. We measured fasting plasma glucose, 2 h postprandial plasma glucose, glycated haemoglobin, complete urine analysis, serum creatinine, blood urea nitrogen, C-reactive protein, urinary albumin/creatinine ratio, estimated glomerular filtration rate using Modification of Diet in Renal Disease Abbreviated Equation, level of TLR2, TLR4, and nuclear NF-κB. In the animal part, the study was conducted on 20 aged (1.5-year old) male wistar rats, the rats were divided into two main groups; group I (control): 10 normal healthy male rats, group II (diabetic): 10 rats with high-fat diet)/streptozotocin-induced diabetes. Blood samples were collected for the determination of fasting plasma glucose, fasting serum insulin, insulin resistance was assessed by calculating the homeostatic model assessment of insulin resistance, blood urea nitrogen, serum creatinine and C-reactive protein and analysis of TLR2, TLR4, and NF-κB in renal tissue was done. Results In the human part of our study: the level of TLRs2, TLR4, and NF-κB was significantly higher in old diabetic patients group than young diabetic patients group and control group. In the animal part of our study: the level of TLRs2 and 4 and NF-κB was significantly higher in diabetic rat group than healthy rat control group. Conclusion TLRs2, TLR4, and NF-κB were higher in old diabetic patients compared with young diabetic patients and normal individuals. These observations significantly added to the emerging role of TLRs in T2DM development and its possible role in the pathogenesis and progression of DN. Also, the present study showed that the TLR system was closely related to the ageing of the kidneys.

Effect of Coelogyne cristata Lindley in alleviation of chronic fatigue syndrome in aged Wistar rats

BackgroundSwarna Jibanti scientifically known as Coelogyne cristata Lindley (Orchidaceae), an orchid mentioned in Ayurvedic medicine is used to promote healthy life span. Objective(s)The present work was planned to study the efficacy of hydro-alcoholic extract of pseudobulbs of C. cristata (CCE) to assess its role on chronic fatigue syndrome (CFS) induced behavioural and biochemical changes in aged Wistar rats compared to Panax ginseng (PG), a prototype anti-stress agent. Materials and methodsCFS was induced by forced swimming for consecutive 21 days for fixed duration (15 min sessions). The criteria of CFS due to fatigue were counted using locomotor activity, depression and anxiety through automated photactometer, immobility time and plus maze activity respectively. Acute toxicity study of CCE (upto 2 g/kg, Limit test) was also performed. For CFS, animals were divided into five groups, naive control, control, CCE treated (25 mg/kg b.w., 250 mg/kg b.w.) and standard PG treated (100 mg/kg b.w.) groups. All drugs were given orally for consecutive 21 days along with CFS. After assessing behavioural parameters, all animals were sacrificed at day 21 and in vivo antioxidant potential of CCE was determined by lipid peroxides, nitrite, catalase (CAT) and superoxide dismutase (SOD) in brain tissue. ResultsCCE was found to be non-toxic. CCE treated aged rats significantly improved (p < 0.001) the spontaneous locomotor movement with respect to control rats, while, decreased the mobility period or depression score. In CFS, CCE also enhanced the time spent (p < 0.001) in open arms while reducing the time spent in closed arm as compared to CFS control, indicating lowering anxiety score. Moreover, marked diminution in lipid peroxidation, nitrite and SOD level was exhibited after CCE treatment and significantly enhanced catalase level significantly (p < 0.01) with respect to CFS control. PG also showed similar actions. ConclusionThe results confirmed the potential therapeutic actions of CCE against experimentally induced CFS in aged rats that might be due to its CNS mediatory antioxidant properties.

Age-Dependent Neurochemical Remodeling of Hypothalamic Astrocytes.

The hypothalamus is a crucial integrative center in the central nervous system, responsible for the regulation of homeostatic activities, including systemic energy balance. Increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions; they participate in the modulation of synaptic transmission, metabolic and trophic support to neurons, immune defense, and nutrient sensing. In this context, disturbance of systemic energy homeostasis, which is a common feature of obesity and the aging process, involves inflammatory responses. This may be related to dysfunction of hypothalamic astrocytes. In this regard, the aim of this study was to evaluate the neurochemical properties of hypothalamic astrocyte cultures from newborn, adult, and aged Wistar rats. Age-dependent changes in the regulation of glutamatergic homeostasis, glutathione biosynthesis, amino acid profile, glucose metabolism, trophic support, and inflammatory response were observed. Additionally, signaling pathways including nuclear factor erythroid-derived 2-like 2/heme oxygenase-1 p38 mitogen-activated protein kinase, nuclear factor kappa B, phosphatidylinositide 3-kinase/Akt, and leptin receptor expression may represent putative mechanisms associated with the cellular alterations. In summary, our findings indicate that as age increases, hypothalamic astrocytes remodel and exhibit changes in their neurochemical properties. This process may play a role in the onset and/or progression of metabolic disorders.

Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner.

Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC) independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6–12 Hz) oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7–12 Hz), related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7–12 Hz range (“Mu-bursts”) in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg) acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABAA receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.

Cyclosomatostatin-Induced Catalepsy in the Aged Wistar Rats: Inhibition by Nicotine

Cyclosomatostatin-Induced Catalepsy in the Aged Wistar Rats: Inhibition by Nicotine