Hippocampus Of Old Rats Research Articles

Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy.

Several studies have indicated that interrupted epigenetic reprogramming using Yamanaka transcription factors (OSKM) can rejuvenate cells from old laboratory animals and humans. However, the potential of OSKM-induced rejuvenation in brain tissue has been less explored. Here, we aimed to restore cognitive performance in 25.3-month-old female Sprague-Dawley rats using OSKM gene therapy for 39days. Their progress was then compared with the cognitive performance of untreated 3.5-month-old rats as well as old control rats treated with a placebo adenovector. The Barnes maze test, used to assess cognitive performance, demonstrated enhanced cognitive abilities in old rats treated with OSKM compared to old control animals. In the treated old rats, there was a noticeable trend towards improved spatial memory relative to the old controls. Further, OSKM gene expression did not lead to any pathological alterations within the 39days. Analysis of DNA methylation following OSKM treatment yielded three insights. First, epigenetic clocks for rats suggested a marginally significant epigenetic rejuvenation. Second, chromatin state analysis revealed that OSKM treatment rejuvenated the methylome of the hippocampus. Third, an epigenome-wide association analysis indicated that OSKM expression in the hippocampus of old rats partially reversed the age-related increase in methylation. In summary, the administration of Yamanaka genes via viral vectors rejuvenates the functional capabilities and the epigenetic landscape of the rat hippocampus.

Resveratrol improves episodic-like memory and motor coordination through modulating neuroinflammation in old rats

Strategies focus on the use of molecules found in food derived from plants as polyphenols, arouse interest for combating aging. The polyphenol resveratrol, due to its antioxidants and anti-inflammatory properties, is increasingly studied, being still unknown their effects on episodic-like memory and motor coordination. This research evaluated the in vivo effect of chronic resveratrol treatment (20 mg/kg/day, i.p, 28 days) in episodic-like memory and motor coordination in non-pathological old rats, comparing with young and old vehicle-treated rats, using the novel object recognition and the rotarod tests. In combination with the analyses of the effect of resveratrol on the immunoreactivity of the main molecular proteins involved in neuroinflammation (SIRT1, SIRT1-75 kDa fragment, NF-κB acetylation) in the hippocampus of these rats. Results suggest a beneficial effect of resveratrol on episodic-like memory and in motor coordination through modulating neuroinflammation, acting on SIRT1 and NF-κB signaling pathway in the hippocampus of old rats.

Daily Consumption of High-Polyphenol Olive Oil Enhances Hippocampal Neurogenesis in Old Female Rats

Objective The aim of this study is to evaluate the effect of daily consumption of high-polyphenol (HP) olive oil on neurogenesis by investigating neuronal cell proliferation and maturation in the hippocampus of old rats, and to evaluate the relationship between neurogenesis, spatial memory, and anxiety-like behavior. Methods A total of 34 female, 20–22-month-old Sprague Dawley rats were divided into three groups: control group, low-polyphenol (LP) group, and high-polyphenol (HP) group. The animals were fed distilled water, LP olive oil and HP-extra virgin olive oil, respectively for 6 weeks using an oral gavage. At 43 days, animals were tested using the Morris Water Maze to evaluate spatial memory, and the Open-field test to evaluate anxiety-like behavior. Neural cell proliferation in the dentate gyrus (DG) was determined by BrdU labeling and Nestin protein expression. Neuronal maturation was determined by NeuN labeling. Synaptic density in the hippocampus and prefrontal cortex was examined by measuring Synaptophysin (SYN) levels. Hippocampal Calbindin levels were measured to assess cellular calcium metabolism. Results Daily consumption of HP olive oil significantly improved cell proliferation and neuronal maturation in the DG of old rats. HP-olive oil significantly increased SYN levels in the prefrontal cortex, and nestin and calbindin levels in the hippocampus (p < 0.05). LP olive oil diet has shown no effect on any parameter (p > 0.05). We also did not find any statistically significant difference between the groups in terms of spatial memory and anxiety-like behavior (p > 0.05). Conclusion Our study is first to show that daily consumption of HP-olive oil enhances hippocampal neurogenesis in old rats, which has been confirmed by proliferation and maturation biomarkers. In addition, increased SYN and calbindin levels showed that the generated cells were also functionally developed in the HP group. We suggest that daily consumption of HP olive oil may have beneficial effects on brain aging by triggering neurogenesis.

Effects of GH on the Aging Process in Several Organs: Mechanisms of Action.

In order to investigate the possible beneficial effects of GH administration on the aging process, 24-month-old rats of both sexes and 10-month-old SAMP8 mice were used. Male rats showed increased fat content and decreased lean body mass together with enhanced vasoconstriction and reduced vasodilation of their aortic rings compared to young adult animals. Chronic GH treatment for 10 weeks increased lean body mass and reduced fat weight together with inducing an enhancement of the vasodilatory response by increasing eNOS and a reduction of the constrictory responses. Old SAMP8 male mice also showed insulin resistance together with a decrease in insulin production by the endocrine pancreas and a reduced expression of differentiation parameters. GH treatment decreased plasma levels and increased pancreatic production of insulin and restored differentiation parameters in these animals. Ovariectomy plus low calcium diet in rabbits induced osteoporosis Titanium implants inserted into these rabbit tibiae showed after one month lesser bone to implant (BIC) surface and bone mineral density (BMD). Local application of GH in the surgical opening was able to increase BIC in the osteoporotic group. The hippocampus of old rats showed a reduction in the number of neurons and also in neurogenesis compared to young ones, together with an increase of caspases and a reduction of Bcl-2. GH treatment was able to enhance significantly only the total number of neurons. In conclusion, GH treatment was able to show beneficial effects in old animals on all the different organs and metabolic functions studied.

EFFECT OF N-STEAROYLETHANOLAMINE ON THE LIPID COMPOSITION OF THE FRONTAL CORTEX AND HIPPOCAMPUS OF THE RAT'S BRAIN AT THE AGING

Aim. To study the possible protective effect of cannabimimetic lipid - N-stearoylethanolamine (NSE) on the lipid composition of the frontal cortex, hippocampus and on the state of episodic memory of old rats. Methods. Extraction of lipids from the tissues of the hippocampus and frontal cortex of rats was performed by the method of Bligh and Dyer. Phospholipids were separated by two-dimensional thin layer chromatography. Methyl esters of fatty acids from lipid extract were obtained by a modified method of Carreau and Dubaco. Quantitative analysis of fatty acid methyl esters was performed by gas-liquid chromatography on an Agilent GC7890 chromatograph with an Agilent 8987 mass detector. The fractions of free and esterified cholesterol were separated by one-dimensional thin layer chromatography. The dry cholesterol residue was analyzed on a Carlo Erba gas-liquid chromatograph. Results. The study of the diacyl (DF) and plasmalogen (PF) forms of phospholipids (PLs) content in the frontal cortex and hippocampus have shown a significant decrease in the plasmalogen form of PE (Phosphatidylethanolamine) (up to 15%) and an increase in its DF, compare to its content in young rats. Administration of NSE to old rats led to a significant increase in PF PE and did not cause significant changes in the content of PF in the composition of other PL of the frontal cortex of the brain and hippocampus. The decrease in the percentage of various phospholipids was found in frontal cortex and hippocampus of old rats: the content of phosphatidylcholine (PC) and phosphatidylinositol (PI) was significantly reduced in the frontal cortex and the decrease of diphosphatidylglycerol (DPG), PI and phosphatidylserine (PS) was found in the hippocampus, compare to the young animals. Administration of NSE to old rats had a different effects on the content of various phospholipids. The increase in the content of PC and PI in the frontal cortex and PS and DPG in the hippocampus is particularly pronounced due to NSE. An increase in the content of saturated fatty acids (FFAs ) and a decrease in the content of unsaturated FFAs in the frontal cortex and hippocampus of old rats also has been found. It has also been found that NSE administration to old rats promoted the growth of the free cholesterol level in the frontal cortex and hippocampus. The results of the New Object Recognition test in old rats have shown that a short-term memory has been improved by NSE. Conclusions. The administration of NSE to old rats causes an increase in PF of PLs in the frontal cortex and hippocampus of the brain, which can be considered as one of the mechanisms of neuroprotective action of NSE in aging. The changes in the phospholipids and fatty acids composition, and free cholesterol level of the frontal cortex and hippocampus of the brain of old rats caused by NSE administration have been shown to be adaptive and restorative. The New Object Recognition Behavioral Test has shown that NSE restores short-term memory in older rats. The obtained results expand the understanding of the mechanisms of biological action of NSE during aging in mammals and create the basis for the development a new drug with geroprotective properties.

The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: An investigation into some signaling pathways related to mitochondria.

Objective(s):High-intensity interval training (HIIT) is a shape of interval training that provides ameliorated athletic capacity and has a good effect on health. Resveratrol is a natural polyphenol abundant in grapes and red wine and has been demonstrated to apply various useful health impacts on the body. This research aimed to evaluate the interactive effects of swimming HIIT and resveratrol consumption on SIRTs 3 & 4, NAD+/NADH, AMPK and SOD2 expression in aged rats.Materials and Methods:In total, forty-five old male albino rats (Wistar) with the age of twenty months were allocated into 5 groups randomly. Control group (Ctrl), Swimming HIIT group (Ex: Exercise), Swimming HIIT with Resveratrol consumption group (R+Ex), Resveratrol consumption group (R) and solvent of resveratrol consumption group (vehicle). R+Ex group accomplished the exercise and consumed resveratrol (10 mg/kg/day, gavage) for 6 weeks.Results:HIIT & resveratrol significantly increased NAD+/NADH, SOD 2 and AMPK in the aged rats. HIIT increased SIRT3, but resveratrol reduced it. As for SIRT4, HIIT decreased it, while resveratrol positively affected it.Conclusion:Resveratrol and HIIT, especially their combination, have anti-oxidant and anti-aging effects on the hippocampus of old rats.

Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents.

ObjectivesAmantadine has been shown to attenuate postoperative learning and memory dysfunction in young adult rats. However, postoperative cognitive dysfunction often occurs in elderly patients. We aimed to determine whether amantadine attenuated postoperative learning and memory dysfunction and whether these effects were associated with improved dendritic arborization in old rodents.MethodsEighteen-month old male C57BL/6J mice or Fischer 344 rats were subjected to right carotid artery exposure (surgery) under isoflurane anesthesia. This age represents an early old stage in rodents. Carotid artery exposure was used to simulate commonly performed carotid endarterectomy in elderly patients. Amantadine was injected intraperitoneally at 25 μg/g once a day for 3 days with the first dose at 15 min before surgery. The animals were tested by Barnes maze and fear conditioning starting one week after the surgery. Hippocampus was harvested for Western blotting and Golgi staining.ResultsSurgery and anesthesia impaired the learning and memory in old mice and rats. Surgery reduced the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), dendritic arborization and spine density in the hippocampus of old rats. These effects were attenuated by amantadine. The effects of amantadine were blocked by intracerebroventricular injection of anti-BDNF antibody or anti-GDNF antibody.ConclusionSurgery and anesthesia impaired learning, memory and dendritic arborization in old rodents that are age relevant to postoperative cognitive dysfunction. These effects may be attenuated by amantadine via preserving the expression of neurotrophic factors.

The treatment of Goji berry (Lycium barbarum) improves the neuroplasticity of the prefrontal cortex and hippocampus in aged rats

The main characteristic of brain aging is an exacerbated inflammatory and oxidative response that affects dendritic morphology and the function of the neurons of the prefrontal cortex (PFC) and the hippocampus. This consequently causes memory loss. Recently, the use of the Goji berry (Lycium barbarum) as an antioxidant extract has provided neuroprotection and neuroplasticity, however, its therapeutic potential has not been demonstrated in aging conditions. The objective of this study was to evaluate the effect of Goji administration on memory recognition, as well as the changes in the dendritic morphology of the PFC and Hippocampus pyramidal neurons in old rats. Goji (3 g/kg) was administrated for 60 days in 18-month-old rats. After the treatment, recognition memory was evaluated using the new object recognition task (NORt). The changes in the neuron morphology of the PFC and hippocampus pyramidal neurons in old rats were evaluated by Golgi-cox stain and immunoreactivity for synaptophysin, glial fibrillary acidic protein (GFAP), caspase-3, 3-nitrotyrosine (3-NT) and nuclear factor erythroid 2-related factor 2 (Nrf2). The rats treated with Goji showed a significant increase in dendritic morphology in the PFC and hippocampus neurons, a greater immunoreactivity to synaptophysin and a decrease in reactive astrogliosis and also in caspase-3, in 3-NT and in Nrf2 in these brain regions was also observed. Goji administration promotes the plasticity processes in the PFC and in the hippocampus of old rats, critical structures in the brain aging process.

Aging is not equal across memory systems.

The present experiments compared the effects of aging on learning several hippocampus- and striatum-sensitive tasks in young (3-4month) and old (24-28month) male Fischer-344 rats. Across three sets of tasks, aging was accompanied not only by deficits on hippocampal tasks but also by maintained or even enhanced abilities on striatal tasks. On two novel object recognition tasks, rats showed impaired performance on a hippocampal object location task but enhanced performance on a striatal object replacement task. On a dual solution task, young rats predominately used hippocampal solutions and old rats used striatal solutions. In addition, on two maze tasks optimally solved using either hippocampus-sensitive place or striatum-sensitive response strategies, relative to young rats, old rats had impaired learning on the place version but equivalent learning on the response version. Because glucose treatments can reverse deficits in learning and memory across many tasks and contexts, levels of available glucose in the brain may have particular importance in cognitive aging observed across tasks and memory systems. During place learning, training-related rises in extracellular glucose levels were attenuated in the hippocampus of old rats compared to young rats. In contrast, glucose levels in the striatum increased comparably in young and old rats trained on either the place or response task. These extracellular brain glucose responses to training paralleled the impairment in hippocampus-sensitive learning and the sparing of striatum-sensitive learning seen as rats age, suggesting a link between age-related changes in learning and metabolic substrate availability in these brain regions.

Neuroprotective Benefits of Aerobic Exercise and Organoselenium Dietary Supplementation in Hippocampus of Old Rats.

The progressive decline of neurological functions, such as learning and memory, is an unavoidable consequence of aging. Our previous work suggested that the combination of physical exercise and a diet supplemented with diphenyl diselenide improves age-related memory decline in rats. The present study investigated the effects of physical exercise and a diet supplemented with diphenyl diselenide on the levels of proteins involved in the hippocampal neuroprotection to figure out the mechanisms related to the beneficial effects of this intervention in aged rats. Male Wistar rats (27months old) were fed daily with standard chow supplemented with 1ppm of diphenyl diselenide and subjected to swimming training with a workload (1% of body weight, 20min/day) for 4weeks. The hippocampus was dissected from the brain and used for the western blot and immunohistochemistry analyses. The results of this study demonstrate that the association of diphenyl diselenide-supplemented diet and swimming exercise increased the levels of proteins involved in neuroprotection and decreased the activation of those related to apoptosis and neuroinflammation in the hippocampus of old rats. This study suggests that physical exercise and a diet supplemented with (PhSe)2 promoted neuroprotection in the hippocampus of aged rats.

Generation of a fusion protein between trastuzumab and unique long-16 binding protein 2 to stimulating immune cells to kill the breast carcinoma in vitro

Objective To research the protective effect of lidocaine on mitochondria damage caused by isoflurane in hippocampus of old rats. Methods The 18-month-old Fisher 344 rats were divided into 3 groups (6 rats per group): control group, 1.2% isoflurane group and 1.2% isoflurane + lidocaine group. The apoptosis was examined through TdT-mediated dUTP nick end labeling (TUNEL), the expression of cysteinyl aspartate-specific protease (Caspase)-3 and B cell lymphoma/leukemia-2 associated X protein (bax)/B cell lymphoma/leukemia-2 (bcl-2) was detected by Western blotting, and mitochondria morphological characteristics were observed through electron microscope. The activity of mitochondrial respiratory chain and the mitochondrial membrane potential were tested. Results By comparison with control group, isoflurane could not only increase apoptosis rate, but also increase the expression of Caspase-3 [(0.11±0.04)% vs. (0.30±0.09)%] and bax/bcl-2 [(0.6±0.2)% vs. (2.4±0.9)%]. However lidocaine reduced the expression of Caspase-3 and bax/bcl-2. As compared with control group, isoflurane depressed the activity of mitochondrial respiratory chain and the mitochondrial membrane potential [(14.1±4.8)% vs. (85.9±3.5)%]. After adding lidocaine, the activity and potential were elevated to (52.5±5.9)%. Conclusion Lidocaine could relieve the neurotoxicity of isoflurane though reducing mitochondria damage in hippocampus of old rats. Key words: Lidocaine; Isoflurane; Mitochondrion; Hippocampus neurons; Apoptosis

Therapeutic potential of IGF-I on hippocampal neurogenesis and function during aging.

In rats, learning and memory performance decline during normal aging, which is paralleled by a severe reduction of the levels of neurogenesis in the hippocampal dentate gyrus (DG). A promising therapeutic strategy to restore neurogenesis in the hippocampus of old rats and their spatial memory involves the use of insulin-like growth factor-I (IGF-I). The peptide exerts pleiotropic effects in the brain, regulating multiple cellular processes. Thus, 4-week intracerebroventricular (ICV) perfusion of IGF-I significantly restored spatial memory and hippocampal neurogenesis in old male rats. Similar results were achieved by ICV IGF-I gene therapy in aging female rats. Thus, the treatment seemed to increase the number of immature neurons in the DG of 28 mo old rats, which was paralleled by an increase in the accuracy of the animals to remember specific patterns, which is known as pattern separation memory. The DG is thought to be the main hippocampal structure involved in pattern separation memory and there is evidence that the level of neurogenesis in the DG is directly related to pattern separation performance in rodents. Summing up, IGF-I emerges as a promising restorative molecule for increasing hippocampal neurogenesis and memory accuracy in aged individuals and possibly, in neurodegenerative pathologies.

Aging-related alterations in the expression and distribution of GluR2 and PICK1 in the rat hippocampus

Deficit in synaptic plasticity in the hippocampus frequently occurs during normal aging. Although the protein level and calcium permeability of AMPARs alter with aging, the alteration of AMPARs and their regulatory proteins during aging are far from understanding. Dynamics of GluR2 subunit are dependent on the function of protein interacting with Cα kinase 1 (PICK1), PKCα and calcineurin (CaN). Here, we firstly show that the expression of PICK1 and CaN B decreased significantly in the hippocampus of old rats compared to that of young and adult rats. The decrease was accompanied by a reduction of GluR2 and PKCα and an increase in CaN A. Next, we found that in young and adult rats, the distribution of PICK1 and GluR2 diffused in the cytoplasm of hippocampal neurons, but closely around perinuclear in the hippocampal neurons of old rats. These results suggest that the expression of GluR2, PICK1, PKCα and CaN B significant decreased in the hippocampus and these alterations may lead to altered distribution of GluR2 and PICK1 during aging.

Determination of protein-bound methionine oxidationin the hippocampus of adult and old rats by LC-ESI-ITMS method after microwave-assisted proteolysis

Protein-bound methionine (Met) oxidation has been associated with normal aging and a variety of age-related diseases, including Alzheimer's disease and Parkinson's disease. Monitoring the changes of protein-bound methionine content in the brain in response to normal aging and oxidative stress is of great interest and could be used as an indicator of oxidative stress of rats in pathological conditions. We have developed a rapid analytical method for the determination of oxidized products of protein-bound methionine in rat brain. The assay involved rapid acid proteolysis with microwave irradiation and solid-phase extraction of the free amino acids followed by LC-ESI-ITMS analysis. Detection was achieved in positive ionization with an ion trap mass spectrometer operating in multiple-reaction monitoring mode. The calibration curves of the analytes were linear (r(2) > 0.99) in the range between 0.098 and 1.560 μg/mL. Intra- and inter-day relative standard deviation percentages were <9% and <8%, respectively. The assay performance was sufficient to support a rapid analytical tool for monitoring brain protein-bound methionine oxidation levels. The content of protein-bound Met and methionine sulfoxide (MetO) in the hippocampus of adult and old rats with or without H(2)O(2) treatment was determined by employing the new method. The content of protein-bound MetO was significantly increased in old rats after exposure to H(2)O(2). This result indicates increased sensitivity to Met oxidation in the hippocampus of old rats.

The effect of sevoflurane anesthesia on cognitive function and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus in old rats

To investigate the effects of sevoflurane on cognitive function in old Sprague-Dawley (SD) rats and the expression of insulin-like growth factor-1 (IGF-1) in CA1 region of hippocampus. Forty Sprague-Dawley rats of 12 months old were randomly divided into five groups: the normal control group; 1.5% sevoflurane I group (be tested after received 1.5% sevoflurane for 1 day); 1.5% sevoflurane II group (be tested after received 1.5% sevoflurane for 7 day); 3.0% sevoflurane I group (be tested after received 3.0% sevoflurane for 1 day) and 3.0% sevoflurane II group (be tested after received 3.0% sevoflurane for 7 day). All SD rats were received 1.5 or 3.0% sevoflurane in a special glass anesthesia box for 2 h respectively, except for the normal control group. Y-maze was used to test the ability of learning and memory after being received sevoflurane for 1 or 7 days at the same moment portion. The altered expression level of IGF-1 in the hippocampus was tested to compare its transcripts by RT-PCR analysis. The results showed that 3% sevoflurane induced the decline of cognitive function and significantly deceased the IGF-1 expression at mRNA levels at 1 day in the 3.0% sevoflurane I group when compared with the normal control group. However, there were no significant difference among the other groups when compared with normal control group. Therefore, administration of sevoflurane might temporally affect the ability of cognitive function of rats through suppressing the IGF-1 expression at mRNA levels in hippocampus.

Effects of long-term fish oil-enriched diet on the sphingolipid metabolism in brain of old rats

An increase of the neutral sphingomyelinase (SMase) activity in the animal brain at old age is associated with a higher expression of the inflammatory marker, interleukin-1β and a cognitive decline. Dietary n − 3 polyunsaturated fatty acids ( n − 3 PUFA) are found to exhibit anti-inflammatory effects and normalize the age- or dementia-related cognitive function decline. In the paper we investigate the ceramide, sphingomyelin (SM) and phosphatidylserine (PS) levels in the hippocampus of 3-month-old-32-month-old rats as well as the correction of sphingolipid turnover in the brain of old rats by means of the dietetic fish oil and PS. To study the lipid turnover, the [ 14C]-labeled SM and palmitic acid were used. The [ 14C]ceramide level significantly increased while those of the [ 14C]SM, SM and PS levels decreased in the hippocampus of aged rats as compared with 3-month-old animals. Treatment of the rats with the fish oil or PS reduced the [ 14C]ceramide content and neutral SMase activity in the hippocampus of the 24-month-old animals with respect to control rats of the same age. These results suggest that dietary n − 3 PUFA can prevent the age-dependent abnormalities of sphingolipid turnover via increased PS content in the hippocampus of old rats.

Changes in glutamate decarboxylase enzyme activity and tau-protein phosphorylation in the hippocampus of old rats exposed to chronic mild stress: Reversal with the neuronal nitric oxide synthase inhibitor 7-nitroindazole

Effects of chronic stress are not completely understood. They may underlie depression and dementia. This study assessed the association between chronic stress, glutamate levels, tau-protein phosphorylation, and nitric-oxide in old rats exposed to chronic mild stress (CMS). Old (> 15 months) male Wistar rats were exposed to CMS. Comparison groups included old and young control rats, young CMS-exposed, and old CMS-exposed rats treated with the neuronal nitric-oxide synthase (nNOS) enzyme inhibitor, 7-nitroindazole (20 mg/kg/day i.p.). Hippocampal glutamate levels and glutamate decarboxylase (GAD) activity were determined and tau protein phosphorylation was assessed. Age was a significant ( p = 0.025) source of variation in glutamate level [811.71 ± 218.1, 665.9 ± 124.9 µmol/g tissue protein (M ± SD) in young and old control rats, respectively]. Old rats exposed to CMS were characterized by an increased risk to develop anhedonia. There was significant ( p = 0.035) decrease in GAD enzyme activity (− 60.06%) and increased tau protein hyperphosphorylation in old rats exposed to CMS compared to control. Administration of 7-nitroindazole to CMS-exposed old rats significantly ( p = 0.002) increased GAD activity, decreased glutamate levels (7.19 ± 3.19 vs. 763.9 ± 91 µmol/g tissue protein; p = 0.0005), and decreased phosphorylation of tau proteins compared to CMS exposed rats.

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB- and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.

The benefits and drawbacks of nicotine exposure in the cortex and hippocampus of old rats

Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24–26 months old (620–700 g) were exposed i.p. to two doses (0.3 and 1 mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory ( p < 0.05), whereas NIC 1 improved both short and long-term memories ( p < 0.05). DNA damage was observed only in hippocampus ( p < 0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus ( p < 0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1 mg/kg) in both tissues ( p > 0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus ( p < 0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered.

Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: Studies on superoxide dismutase isoenzymes and protein oxidation status

This study was aimed at determining the effect of exercise and vitamin E on age-associated changes in the superoxide dismutase (SOD), lipid (LPO) and protein oxidations (PO) in the cerebral cortex (CC), cerebellum (CB) and hippocampus (HC) of rat brain. For this, male Wistar albino rats of 4- (adult), 12- (middle-age) and 18-month (old) of age were orally supplemented with vitamin E and swim trained at 3% intensity for 30 min/day, 5 days/week, and for a period of 30 days. Reduced total SOD was evident with age in the CC while it was highest in the HC of old rats. Vitamin E elevated SOD in the old trainees. Mn-SOD increased in the middle-age and old trainees and Cu Zn-SOD increased in the supplemented and trained adults. Age-related and region-specific increase in protein carbonyl (PrC) content with decreased sulphydryl (P-SH) was seen. Vitamin E reduced PrC and advanced oxidation of protein products (AOPP) in all ages, and appreciably in the HC and CB. Our study emphasizes a correlation between mitochondrial H 2O 2 generation, Mn-SOD activity and MDA level, and reveals in part an age-related increase in lipid peroxidation and protein oxidation, and that may occur under conditions such as vitamin E deficiency.