Untreated Aged Rats Research Articles

Probiotic Improves Skin Oxidation, Elasticity, and Structural Properties in Aging Rats.

Skin aging, which affects all living organisms, is associated with oxidative stress. Probiotics exhibit antioxidant properties by producing reactive metabolites that counter oxidative stress. We hypothesized that Limosilactobacillus fermentum USM 4189 (LF 4189) has antioxidative properties and may prevent skin aging. In the present study, we used a D-galactose senescence-induced rat model to evaluate the potential antioxidative capability of LF 4189. The results indicated that rats administered LF 4189 exhibited increased plasma antioxidative activity (P=0.004), lipid peroxidation capacity (P=0.007), and skin elasticity compared with untreated aged rats (P=0.005). LF 4189 prevented telomere length shortening (P<0.05), indicating the potential to prevent senescence. A higher apoptotic activity was observed in old rats compared with young rats, whereas LF 4189 reduced the expression of four antioxidative enzyme genes that function as radical scavengers (all P<0.05), suggesting that the LF 4189 group had a reduced need to scavenge free radicals. Our findings indicate the potential of probiotics, such as LF 4189, as an anti-aging dietary intervention with antioxidant potential to improve skin health.

Intake of Fluted Pumpkin Seeds Rebalances Oxidative Stress Parameters in the Aged Rat’s Testes

The effect of fluted pumpkin seeds (FPS) consumption on the antioxidant status of the testes of aged Wistar rats was evaluated in this study. Sixty (50 aged, 6 months old, and 10 young, 2 months old) rats were divided into six groups of 10 per each group. Testosterone (15 mg kg-1 body weight, once weekly for 40 days) was injected intraperitoneally and used as positive control. FPS intake (50, 100, and 200 mg kg-1 body weight) or vehicle control (corn oil) were administered orally, twice weekly for 40 days and compared with the untreated aged and young control rats. Changes in antioxidant status in the testis of the aged rats was reflected as increased superoxide dismutase and catalase activities and glutathione and decreased lipid peroxidation levels which were attenuated more efficiently by the lowest dose FPS (50 mg kg-1 body weight). Additionally, nitrite concentration that was found to be diminished in the aged rats was raised to the young control values after intake of the FPS (50 mg kg-1 body weight). As expected, testosterone injection increased endogenous testosterone concentration and also remained higher in the untreated aged animals than in young control and treated aged rats. In conclusion, compromised antioxidant defense system of the testes that is associated with ageing could be reversed to the status of the young control by the intake of FPS.

Amelioration of Age-Related Multiple Neuronal Impairments and Inflammation in High-Fat Diet-Fed Rats: The Prospective Multitargets of Geraniol.

Neuroinflammation is documented to alter brain function as a consequence of metabolic changes linked with a high-fat diet (HFD). The primary target of this study is to see how geraniol is effective in manipulating age- and diet-associated multiple toxicity and neuroinflammation in HFD-fed rats. Sixty-four adult male Wistar rats were partitioned into two groups: Group 1 (untreated normal young and aged rats) and Group 2 (HFD-fed young and aged rats) that received HFD for 16 weeks before being orally treated with geraniol or chromax for eight weeks. The results revealed a dropping in proinflammatory cytokines (TNF-α and IL-6) and leptin while boosting adiponectin in geraniol-supplemented rats. The liver, kidney, and lipid profiles were improved in geraniol-HFD-treated groups. HFD-induced brain insulin resistance decreased insulin clearance and insulin-degrading enzyme (IDE) levels significantly after geraniol supplementation. Geraniol suppressed acetylcholinesterase (AChE) activity and alleviated oxidative stress by boosting neuronal reduced glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activities. It lowered malondialdehyde concentration (TBARS), nitric oxide (NO), and xanthine oxidase (XO) and restored the structural damage to the brain tissue caused by HFD. Compared with model rats, geraniol boosted learning and memory function and ameliorated the inflammation status in the brain by lowering the protein levels of IL-1β, iNOS, NF-κBp65, and COX-2. In addition, the expression levels of inflammation-related genes (MCP-1, TNF-α, IL-6, IL-1β, and IDO-1) were lessened significantly. Remarkably, the supplementation of geraniol reversed the oxidative and inflammation changes associated with aging. It affected the redox status of young rats. In conclusion, our results exhibit the effectiveness of dietary geraniol supplementation in modifying age-related neuroinflammation and oxidative stress in rats and triggering off the use of geraniol as a noninvasive natural compound for controlling age- and diet-associated neuronal impairments and toxicity.

Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype

ObjectiveTo assess the functional role of Hyperpolarization-activated cyclic nucleotide-gated gated channel (HCN) subtypes in the aging bladder phenotype characterized by diminished bladder volume sensation (BVS) with or without the detrusor instability (DI). MethodsExpression of HCN subtypes was examined by quantitative RT-PCR and Western blot in aged male Fisher 344 rats (n = 15) and young rats (n = 15). Nocturnal urination and awake cystometry (CMG) were assessed in presence and absence of a steady state HCN channel blockade achieved with daily oral gavage of vehicle or Ivabradine (HCN blocker) 6 mg/kg for 7 days. ResultsThe association of BVS with the age-related downregulation (~30%) of cAMP sensitive HCN1, HCN2 subtypes, and (~50%) upregulation of cAMP insensitive HCN3 subtype is evinced by the doubling in the mean urine volume of nocturnal voids (0.82 ± 0.22 mL vs 0.41 ± 0.12 mL; n = 10; p < 0.05) predicting an age-related rise in the micturition volume threshold (p < 0.0001) in CMG, which is raised further by Ivabradine treatment (p < 0.0005). Ivabradine also doubled non-voiding contractions (NVC) and maximum voiding pressure (MVP) in young and aged rats, respectively (p < 0.0001) to abolish the age-related, innate two -fold elevation in NVC not accompanied with MVP rise in untreated aged rats (p < 0.005). ConclusionThe age-related HCN downregulation is mechanistically linked to the exhibition of aging bladder phenotype with the manifestation of DI following steady state blockade of HCN channels in Ivabradine treated young rats. The amplification of MVP in aged rats mediated by FDA approved Ivabradine hints at potential repurposing opportunity in detrusor underactivity.

Environmental enrichment modulates silent information regulator 1 (SIRT1) activity to attenuate central presbycusis in a rat model of normal aging.

Age-related hearing loss (ARHL) is sensory impairment in the elderly. This study aimed to identify a critical molecular mechanism that can maintain young phenotypes. We focused on the effect of exposure to environmental enrichment (EE) for 12weeks in the central auditory pathway and limbic system of aged rats. The effects of EE were compared with the effects of dexamethasone administration. We found that in 74-week-old rats hearing function was significantly reduced and the number of neuronal specific nuclear protein (NeuN)-positive cells was decreased by 10-15% in the auditory cortex, amygdala, and hippocampus. EE exposure did not significantly affect the number of neurons, but DX administration significantly decreased their numbers in the amygdala compared with untreated aged rats. Both treatments reduced inducible nitric oxide synthase (iNOS) expression in the auditory pathway and limbic system. Exposure to EE significantly increased silent information regulator 1 (SIRT1) expression and activity, and nicotinamide phosphoribosyltransferase (NAMPT) concentration. In this study, the exposure to EE resulted in attenuated age-related hearing loss accompanied by reduction of iNOS expression and increase SIRT1 activity and NAMPT level. These data showed that EE may be a potential therapeutic to prevent ARHL.

PD27-07 BEDSIDE TO BENCHTOP RESEARCH UNCOVERS THE FUNCTIONAL ROLE OF HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED GATED (HCN) CHANNELS IN AGING BLADDER PHENOTYPE

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-07 BEDSIDE TO BENCHTOP RESEARCH UNCOVERS THE FUNCTIONAL ROLE OF HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED GATED (HCN) CHANNELS IN AGING BLADDER PHENOTYPE Nishant Singh, Irina Zabbarova, Anthony Kanai, Christopher Chermansky, Naoki Yoshimura, and Pradeep Tyagi Nishant SinghNishant Singh More articles by this author , Irina ZabbarovaIrina Zabbarova More articles by this author , Anthony KanaiAnthony Kanai More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Pradeep TyagiPradeep Tyagi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aging bladder phenotype in detrusor overactivity, detrusor underactivity or detrusor hyperactivity with impaired contractility patients is characterized by detrusor instability with or without the loss of bladder volume sensitivity. Since separate studies reported age related downregulation of Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in mouse and human bladder, we examined the functional significance of age related reduction in HCN activity with multiple oral dosing of FDA approved HCN blocker, Ivabradine. METHODS: Aged male Fisher 344 rats (n=15) and young rats of both genders (n=15) were left untreated or treated daily with oral gavage of either vehicle or Ivabradine 6mg/kg (n=5) for 7 days prior to assessing nocturnal urination followed by awake cystometry on 7th day and quantitative RT-PCR and Western blot of HCN subtypes of untreated aged and young rats. RESULTS: Untreated aged aged rats (n=10) voided nearly double the volume of individual voids of young rats at night time (0.82±0.22 mL vs 0.41±0.12 mL, p<0.05), which was confirmed by a significant increase (p<0.05) in the micturition volume threshold (VT) in awake cystometry of aged rats. Increase in VT of aged rats coincided with a doubling of non-voiding contraction (NVC) frequency (p<0.05) while maximum voiding pressure (MVP) did not change with age. The age- related alterations in cystometry parameters correlated with the significant downregulation of cAMP sensitive HCN1and HCN2 subtype (40%) and the upregulation of cAMP insensitive HCN3 (60%) subtype. Ivabradine treatment significantly increased the VT (p<0.005), NVC frequency (p<0.001) and MVP (p<0.0001) in young and aged rats to different extents. CONCLUSIONS: A critical role for the altered bladder expression of HCN subtypes in the manifestation of aging bladder phenotype is supported by the dramatic changes in the bladder function following pharmacological blockade of HCN channels in young rats. The dramatic effect of Ivabradine on VT and MVP of aged rats in this bedside to benchtop research provides a basis for the therapeutic benefit of Ivabradine on detrusor underactivity of a male patient (Int Urol Nephrol, 40: 333, 2008). Source of Funding: NIA- AG062971 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e446-e446 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nishant Singh More articles by this author Irina Zabbarova More articles by this author Anthony Kanai More articles by this author Christopher Chermansky More articles by this author Naoki Yoshimura More articles by this author Pradeep Tyagi More articles by this author Expand All Advertisement Loading ...

Combination of ellagic acid and trans-cinnamaldehyde alleviates aging-induced cognitive impairment via modulation of mitochondrial function and inflammatory and apoptotic mediators in the prefrontal cortex of aged rats.

Cognitive impairments are associated with advancing age. Trans-cinnamaldehyde (CIN) and ellagic acid (ELA) have multiplex activities to reduce various age-related cognitive disorders. In this study, we investigated the effects of these compounds separately or in combination on the cognitive outcomes, mitochondrial function, and inflammatory and apoptotic mediators in aged male Wistar rats. Thirty-two old (22 months old) and eight young (5 months old) rats were randomly allocated to five groups of young control, aged control, ELA-aged, CIN-aged, and ELA + CIN-aged. ELA (15 mg/kg, orally) and CIN (50 mg/kg, intraperitoneally) separately or in combination were administered for 1 month in aged animals. Spatial memory and cognitive activity were evaluated by the Barnes maze and novel object recognition tests. Mitochondrial function (its reactive oxygen species [ROS], mitochondrial membrane potential and ATP level), pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6 and pro-apoptotic caspase 3 and Bax, and anti-apoptotic Bcl2 levels and their ratio were assessed in the prefrontal cortex. Behavioral results revealed that CIN separately or in combination with ELA significantly alleviates aging-induced memory impairment. Moreover, co-administration of agents effectively decreased inflammatory cytokines, cleaved-caspase 3, Bax and Bax/Bcl2 levels, mitochondrial ROS production, and mitochondrial membrane depolarization and increased Bcl2 and ATP level as compared with untreated aged control rats. Combination therapy was greater than those of individual treatments in all parameters. Therefore, combination therapy with CIN and ELA improved aging-induced cognitive impairment through anti-inflammatory, anti-apoptotic, and mitochondrial-boosting effects in aged rats.

Adipose-derived stem cells improve erectile function partially through the secretion of IGF-1, bFGF, and VEGF in aged rats.

Adipose-derived stem cells (ADSCs) have recently been considered as a promising therapy for erectile dysfunction (ED). However, the mechanism of ADSC-based therapy is unclear. Insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed invitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment with labeled ADSCs or PBS. Eight additional 5-month-old rats were used as a young rat group. At 2weeks post-transplantation, all rats were analyzed for erectile function, cavernous IGF-1, bFGF and VEGF levels, and penile histology. Conditioned medium and co-culture systems were used in cell experiments to detect how growth factors act on corpus cavernosum smooth muscle cells (CCSMCs) under oxidative stress conditions via crystal violet staining and immunofluorescence staining. We found that ADSCs secreted significantly higher IGF-1, bFGF, and VEGF levels in culture medium compared with basal medium. Compared with young rats, untreated aged rats had significantly lower Max ICP/MAP and ADSC treatment significantly increased the ratio. Immunofluorescence staining demonstrated a small number of labeled ADSCs in the corpus cavernosum. The untreated aged rats showed significantly decreased cavernous IGF-1, bFGF, and VEGF levels and significantly decreased contents of cavernous smooth muscle and endothelium compared with young rats. ADSC treatment partially normalized these alterations. In cell experiments, the groups receiving growth factor neutralizing antibody separately or combined had significantly decreased numbers of CCSMCs compared with control groups. These results indicated that ADSC treatment may improve aging-related ED partially through the secretion of IGF-1, bFGF, and VEGF.

Alleviating effects of various concentrations of ethanolic extract of Lycopodium clavatum on aging induced testicular pathology in wistar albino rats

Delayed paternity in the modern society and decreased sexual activity provides reason to research on the effects of ageing on male reproductive system and their possible treatment modalities. The crude ethanolic extract of Lycopodium clavatum commonly known as “club moss” has been reported to have good antioxidant properties. Traditionally lycopodium is used to treat sexual complaints of old aged men and is known to increase their ‘potency’ and considered as the ‘balm of old man’. However there is no scientific validation to confirm this effect. To analyze the efficacy of ethanolic extract of Lycopodium clavatum on aging induced alteration in testicular function and to find its effective therapeutic concentration. Aged male wistar albino rats (24 months) were randomly divided into four groups (n=12), first group received distilled water, and the other three groups received ethanolic extract of Lycopodium clavatum at dosage of 250, 500, 1000 mg / kg. b.w daily for 60 days by gavage. At the end of experimental period, serum testosterone was estimated. Sperm parameters including count, viability, motility, membrane permeability and nuclear condensation were done. Biochemical analyses of testicular antioxidants were done. Testicular mRNA expression of antioxidants and apoptotic genes were estimated by qPCR. The results were statistically analysed. Aging induced pathological changes were noted in the aged untreated animals. Beneficial effects were significant in Lycopodium clavatum treated groups when compared to untreated aged rats. Depleted testosterone level in untreated aged rat was improved in all the treated rats however, significant improvement was seen with 500mg dosage. Sperm parameters were significantly improved in aged rats with 500 mg dosage when compared to the other two treated aged groups i.e. 250 & 1000mg. The gene expression studies emphasized the maximum beneficial effects under 500mg dosage. This observation confirms that Lycopodium clavatum has therapeutic effect under aging induced reproductive disorder and the effect seem to be dosage dependent. Thus results signifies that finding effective dose for given animal is a key factor for maximum therapeutic outcome.

Epigallocatechin-3-gallate ameliorates erectile function in aged rats via regulation of PRMT1/DDAH/ADMA/NOS metabolism pathway.

Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg−1, and 100 mg kg−1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMT1/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure (MAP) was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.

Author's response to RE: Testosterone treatment is a potent tumor promoter for the rat prostate.

I am very concerned by the final statement in the comments by Dr Traish, Dr Morgentaler, and Dr Khera about my report on the carcinogenic and tumor promoting effects of testosterone treatment in male rats that “comments on T therapy based on results from rodents do not belong in this report” (1). Results from studies in rodents are used by the Food and Drug Administration and Environmental Protection Agency, as well as by their European counterparts and international organizations, such as the International Agency for Research on Cancer (World Health Organization), to evaluate the carcinogenic risk to humans of exposures to drugs and other chemicals. A statistically significant increase in the occurrence of malignant tumors in such studies is considered an indication that the drug or chemical tested may be carcinogenic to humans. Typically, drugs in development for medical use that test positive in such studies are not pursued further, and other chemicals that cause malignancies in rodent experiments are regulated on the basis of the study results. Testosterone treatment significantly increased the number of animals with malignant tumors and caused prostate carcinomas in my study and others, quoted in my article, have also found such a prostate tumor response. Prostate tumors are extremely rare in untreated aged Wistar rats, including the Cpb:WU strain used in my study, and finding rare malignancies in rodents exposed to chemicals is commonly considered a strong indication that the compound tested is a rodent carcinogen. After a single carcinogen exposure to cause DNA damage and mutations in the prostate, long-term testosterone treatment caused a massive prostate cancer response in my study, even at a dose that did not significantly elevate circulating testosterone. This tumor response of WU rats to N-methyl-N-nitrosourea plus testosterone treatment has been remarkably stable for over 25 years, indicating that “genetic drift” is not a problem. These findings, taken together, are thus clear reason to be concerned about the risk of prostate cancer in testosterone-treated men, and they form the basis for the last sentence in my report, which disturbed Dr Traish, Dr Morgentaler, and Dr Khera, who left out the beginning of that sentence: “Until adequate human studies are available.”

MP47-15 ADIPOSE-DERIVED STEM CELLS IMPROVE ERECTILE FUNCTION THROUGH SECRETION OF INSULIN-LIKE GROWTH FACTOR-1 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN AGED RAT

INTRODUCTION AND OBJECTIVES: Adipsoe-derived stem cells (ADSCs) have been recently considered promising therapy for erectile dysfunction (ED). However, the mechanism of ADSCsbased therapy remains to be elucidated. The aim of this study was to determine whether transplantation of ADSCs was capable of resolving aging-related ED, and to investigate its underlying mechanisms. METHODS: Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed in vitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment regiments with CM-DiI labeled ADSCs or PBS. Eight additional 5-month-old rats were used as young rats group. At 2-week post-transplantation, all the rats were analyzed for erectile function, cavernous IGF-1 and VEGF levels, and penile histology. The IGF-1 and VEGF levels of ADSCs-conditioned medium and penile tissues were determined by an enzyme-linked immunosorbent assay (ELISA). The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to evaluate erectile function. Immunofluorescence staining was used to evaluate the number of ADSCs, and the contents of cavernous smooth muscle and endothelium. RESULTS: ADSCs could secrete a large amount of IGF-1 and VEGF in culture medium compared to basal medium (P<0.05). Compared to the young rats, the untreated aged rats showed significantly lower Max ICP/MAP (P<0.05) and ADSCs treatment significantly increased the ratio (P<0.05). Immunofluorescence staining demonstrated that there was only a small number of CM-DiI labeled ADSCs found in corpus cavernosum. The corpus cavernosum of untreated aged rats showed decreased IGF-1 and VEGF levels, and the contents of cavernous smooth muscle and endothelium compared to young rats (P<0.05). ADSCs treatment partially normalized these alterations (P<0.05). CONCLUSIONS: ADSCs treatment may improve aging-related ED partially through secretion of IGF-1 and VEGF.

Mild Sensory Stimulation Protects the Aged Rodent From Cortical Ischemic Stroke After Permanent Middle Cerebral Artery Occlusion

BackgroundAccumulated research has shown that the older adult brain is significantly more vulnerable to stroke than the young adult brain. Although recent evidence in young adult rats demonstrates that single-whisker stimulation can result in complete protection from ischemic damage after permanent middle cerebral artery occlusion (pMCAO), it remains unclear whether the same treatment would be effective in older animals.Methods and ResultsAged rats (21 to 24 months of age) underwent pMCAO and subsequently were divided into “treated” and “untreated” groups. Treated aged rats received intermittent single-whisker stimulation during a 120-minute period immediately after pMCAO, whereas untreated aged rats did not. These animals were assessed using a battery of behavioral tests 1 week before and 1 week after pMCAO, after which their brains were stained for infarct. An additional treated aged group and a treated young adult group also were imaged with functional imaging. Results demonstrated that the recovery of treated aged animals was indistinguishable from that of the treated young adult animals. Treated aged rats had fully intact sensorimotor behavior and no infarct, whereas untreated aged rats were impaired and sustained cortical infarct.ConclusionsTaken together, our results confirm that single-whisker stimulation is protective in an aged rodent pMCAO model, despite age-associated stroke vulnerability. These findings further suggest potential for translation to the more clinically relevant older adult human population. (J Am Heart Assoc. 2012;1:e001255 doi: 10.1161/JAHA.112.001255.)

Effects of Aging and Anti-Aging Hormones on The Kidney, The Thyroid Functions and The Histology of The Testis of Male Albino Rats

Introduction The present study was carried out to evaluate the effect of aging and anti-aging hormones on the kidney, the thyroid and the testis of aged male albino rats from the physiological and histological points of view. Material & Methods Thirty five male rats were used in the present study. They were allocated into five groups. The first group (5months old) served as control group and the other remaining groups are (18 months old). The second group 1 ml/kg b.w. corn oil intramuscular injection through a period of two weeks .The third group received 2mg/kg b.w. of melatonin hormone orally daily for two weeks. The fourth group received 0.57 mg/kg b.w. of testosterone hormone via intramuscular injection through two weeks. The fifth group received the same dose of both hormones (Melatonin & Testosterone) for two weeks. Some biochemical parameters of the kidney, the thyroid and histological structure of the testis were examined. Results The untreated aged group showed insignificant change in urea level with highly significant decrease in creatinine, T3 and T4hormones levels.The melatonin treated group showed significant decrease in urea level with highly significant decrease in creatinine, T3 and T4 hormones. The testosterone treated group showed highly significant increase in urea, T3 and T4hormones and highly significant decrease in creatinine level. Whereas, fifth group showed significant decrease in urea accompanied with a highly significant decrease in creatinine and highly significant increase in T3 with a significant increase in T4. The histological changes induced by aging and anti-aging hormones included intertubular haemorrhage, odematous areas present between the seminiferous tubules. The interstitial tissue was degenerated. The degenerated seminiferous tubules revealed maturation arrest in late-stage spermatides. Conclusion In conclusion, aging and anti-aging hormones administration into adult male rats exerts a clear effect on the kidney and the thyroid functions and on the testicular structure. On the other hand, amelioration in T3 &T4 serum level was found in anti-aging treated rats compared with untreated aged rats.

Korean Red Ginseng Up-regulates C21-Steroid Hormone Metabolism via Cyp11a1 Gene in Senescent Rat Testes

Ginseng (Panax ginseng Meyer) has been shown to have anti-aging effects in animal and clinical studies. However, the molecular mechanisms by which ginseng exerts these effects remain unknown. Here, the anti-aging effect of Korean red ginseng (KRG) in rat testes was examined by system biology analysis. KRG water extract prepared in feed pellets was administered orally into 12 month old rats for 4 months, and gene expression in testes was determined by microarray analysis. Microarray analysis identified 33 genes that significantly changed. Compared to the 2 month old young rats, 13 genes (Rps9, Cyp11a1, RT1-A2, LOC365778, Sv2b, RGD1565959, RGD1304748, etc.) were up-regulated and 20 genes (RT1-Db1, Cldn5, Svs5, Degs1, Vdac3, Hbb, LOC684355, Svs5, Tmem97, Orai1, Insl3, LOC497959, etc.) were down-regulated by KRG in the older rats. Ingenuity Pathway Analysis of untreated aged rats versus aged rats treated with KRG showed that the affected most was Cyp11a1, responsible for C21-steroid hormone metabolism, and the top molecular and cellular functions are organ morphology and reproductive system development and function. When genes in young rat were compared with those in the aged rat, sperm capacitation related genes were down-regulated in the old rat. However, when genes in the old rat were compared with those in the old rat treated with KRG, KRG treatment up-regulated C21-steroid hormone metabolism. Taken together, Cyp11a1 expression is decreased in the aged rat, however, it is up-regulated by KRG suggesting that KRG seems enhance testes function via Cyp11a1.

Etazolate improves performance in a foraging and homing task in aged rats

Etazolate is a phosphodiesterase 4 (PDE4) inhibitor and GABAA receptor modulator that also stimulates alpha-secretase activity and neurotrophic soluble amyloid precursor protein (sAPPalpha) production, currently developed as a possible Alzheimer's disease therapeutic. In this study two doses of etazolate were tested for cognitive effects in normally aged rats, using a complex spatial learning and memory task that emphasized two naturally occurring behaviors in rodents, foraging for food and returning large pieces of found food to a safe home location. Both etazolate doses completely prevented both (1) a foraging deficit that developed in untreated aged rats over the course of the test, as well as (2) a trial-specific deficit in memory for previously visited food locations that also developed over the course of the test in untreated aged rats. Both doses also significantly reduced a separate memory deficit for changing locations of the animals' home box, plus completely prevented a significant tendency for untreated aged animals to attempt entry into similar-appearing but incorrect home boxes. The combined behavioral data demonstrate positive effects of etazolate on separate age-related cognitive deficits, using a complex task based on naturally occurring rodent behaviors.

Enhancement of Learning and Memory by Elevating Brain Magnesium

Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.

Abnormal Cortical Cells and Astrocytomas in the Eker Rat Model of Tuberous Sclerosis Complex

In patients with tuberous sclerosis complex (TSC), a wide range of neurologic abnormalities develop, including mental retardation and seizures. Brains from TSC patients are characterized by the presence of cortical tubers, large dysmorphic neurons, and abnormal cytomegalic cells. Although analysis of human TSC brain samples led to the identification of these abnormal cell types, very little is known about how these cells function. In an effort to model TSC-associated CNS abnormalities (and ultimately to analyze the electrophysiologic properties of abnormal cells), we examined Eker rats carrying a Tsc2 mutation. Anatomic studies, including standard histologic stains and immunocytochemistry, were performed on young Eker rats exposed to a carcinogen in utero or aged untreated Eker rats (18-24 months old). Pregnant TSC2+/- females were injected once a day with hydroquinone (HQ), and offspring were killed at postnatal day P14 or P28. Coronal tissue sections throughout the CNS were prepared and stained for cresyl violet. In separate studies, brains of old untreated Eker rats were sectioned for anatomic analysis by using standard immunohistochemical techniques. Tissue sections stained with cresyl violet did not reveal any gross differences between HQ-treated Eker (Tsc2Ek/+) rats and siblings (Tsc2+/+). However, two classes of abnormal giant cells were observed in brain sections from untreated aged Eker rats: (a) large dysmorphic pyramid-like cells immunoreactive for NeuN, tuberin, and EAAC-1 in layers IV-VI; and (b) abnormal cytomegalic cells immunoreactive for glial fibrillary acidic protein (GFAP), vimentin, and nestin in deep cortical layers or along the white matter. In addition, large subependymal astrocytomas were observed in four animals. Our data suggest that cortical tuber formation in Eker rats is a rare event and that prenatal exposure to a nongenotoxic carcinogen such as HQ is not sufficient to induce tuber formation. However, with advanced age, an increased likelihood of astrocytoma formation and the emergence of dysmorphic neurons and cytomegalic cells in the Eker rat brain might exist; each of these abnormalities mimics those seen clinically and could contribute to neurologic problems associated with TSC. Further analysis of this rodent model may be warranted.

Reduction in levels of amphiphysin 1 mRNA in the hippocampus of aged rats subjected to repeated variable stress

Various neurobiological studies of aging indicate that elevated levels of circulating glucocorticoids lead to hippocampal vulnerability to stress, though little is known about the molecular mechanism underlying stress vulnerability in the elderly. We have compared the gene expression profiles in the hippocampus of aged (20 months) and adult (3 months) rats in response to repeated variable stress (RVS) for 4 days, using a cDNA array technique and real-time quantitative PCR, to identify putative genes involved in the mechanism of stress vulnerability in the elderly. We found a significant decrease in the levels of amphiphysin 1 mRNA in aged rats subjected to RVS compared with treated and untreated adult rats or to untreated aged rats. Similarly, we found a significant decrease in hippocampal levels of amphiphysin 1 mRNA in aged rats subjected to RVS for 8 days, but not in those subjected to a single VS. These findings suggest that the decrease in the hippocampal levels of amphiphysin 1 mRNA in response to repeated stress may be involved in the stress vulnerability in the elderly, and may lead to the disturbance of learning and memory under stressful conditions in the elderly.

Chronic converting enzyme inhibition normalizes QT interval in aging rats.

The aim of the present study was to investigate the effects of converting enzyme inhibition by captopril on ECG parameters in aged rats. Four-month-old male rats received captopril dissolved in tap water (0.5 mg/l) or tap water for 2 or 20 months. At the end of treatment, under anesthesia, RR and PR interval, P wave and QRS duration, QT and corrected QT interval were measured in all animals. On the following day, chronic ECG (lead II) recordings were performed to quantify supraventricular (SVPB) or ventricular premature beats (VPB). After sacrifice, the hearts were removed and weighed. RR interval was similar in young and untreated aged rats, but significantly larger in aged rats treated with captopril. P wave and QRS length did not differ among groups. PR interval was significantly larger in old than in young rats and was not affected by captopril. Corrected QT interval was larger in aged than in young rats (117 +/- 4 vs 64 +/- 6 ms, P<0.05) and was reduced by captopril (71 +/- 6 ms, P<0.05). VPB were absent in young rats and highly frequent in untreated old animals (8.4 +/- 3.0/30 min). Captopril significantly reduced VPB in old rats (0.3 +/- 0.1/30 min, P<0.05). The cardiac hypertrophy found in untreated aged rats was prevented by captopril (3.44 +/- 0.14 vs 3.07 +/- 0.10 mg/g, P<0.05). The beneficial effects of angiotensin converting enzyme inhibition on the rat heart during the aging process are remarkable.