Modulatory Role of Glutathione Monoester in Augmenting Age-Associated Neuronal Antioxidant System

An ever-increasing number of reports show the involvement of free radicals in the functional and structural changes occurring in the brain as a part of the normal aging process. This study aimed to assess the potential efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on memory and the antioxidant defense system and lipid peroxidation in discrete brain regions such as cortex, striatum, and hippocampus of young and aged rats. Age-associated decline in memory and activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione, vitamin E, and vitamin C, and elevated levels of lipid peroxidation and oxidized glutathione, were observed in all the brain regions studied (p < .001). GME administration was effective in restoring the antioxidant status and in decreasing lipid peroxidation level in aged rat brain regions.     

Oral supplementation of Lanthanum Zirconate nanoparticles moderately affected behavior but drastically disturbed leukocyte count,serum cholesterol levels and antioxidant parameters from vital organs of albino mice in a gender specific manner

Lanthanum Zirconate nanoparticles (NPs) are used in blades of gas turbine engines to thermally insulate them and to protect them against hot and corrosive gas streams. However, the information regarding their biocompatibility is limited. The present study was aimed to report the effect of Lanthanum Zirconate NPs on selected aspects of behavior, serum biochemistry, complete blood count and antioxidant parameters from vital organs of albino mice in a gender specific manner. Albino mice, seven weeks old, were orally treated with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles for consecutive 22 days. Saline treated control groups were maintained in parallel. It was observed that rearing frequency was significantly decreased (P =?0.01) in NPs treated male mice. Complete blood count analysis indicated that NPs treated female mice had significantly reduced white blood cells (P =?0.05) and lymphocytes count (P =?0.03). NPs treated male had significantly reduced serum cholesterol levels (P =?0.05) than control group. It was observed that Superoxide dismutase concentrations in liver (P?=?0.025) and kidney (P?=?0.008), Malondialdehyde concentrations in liver (P =?0.044) of female and Malondialdehyde concentrations in kidney (P <?0.001) and brain (P <?0.001) and catalase concentrations in liver (P =?0.05) of NPs treated male mice were significantly higher than their respective control groups.. In conclusion, we are reporting that oral supplementation with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles can affect the behavior, leukocyte count, serum cholesterol and antioxidant metabolites from vital organs of albino mice in a gender specific manner.     

Protective effects of N-acetylcysteine on 3, 4-methylenedioxymethamphetamine-induced neurotoxicity in male Sprague–Dawley rats

Exposure to 3, 4-methylenedioxymethamphetamine (MDMA) leads to spatial memory impairment and hippocampal cell death. In the present study we have examined the protective effects of N-acetyl-L-cysteine (NAC) on MDMA-induced neurotoxicity. A total of 56 male Sprague Dawley rats (200–250 g) received twice daily intraperitoneal (IP) injections of 5, 10 or 20 mg/kg MDMA plus NAC (100 mg/kg). Rectal temperatures were recorded before and after daily treatment. We used a Morris water maze (MWM) to assess spatial learning and memory. At the end of the study rats’ brains were removed, cells were counted and the level of Bcl-2, Bax and caspase-3 expression in the hippocampi were measured. NAC pretreatment significantly reduced MDMA-induced hyperthermia. In the MWM, NAC significantly attenuated the MDMA-induced increase in distance traveled; however the observed increase in escape latency was not significant. The decrease in time spent in the target quadrant in MDMA animals was significantly attenuated (p?<?0.001, all groups). NAC protected against MDMA-induced cell death and the up -regulation of Bax and Caspase-3, in addition to the down-regulation of Bcl-2. This data suggested a possible benefit of NAC in the treatment of neurotoxicity among those who use MDMA.     

Effects of adenosine A2a receptor agonist and antagonist on hippocampal nuclear factor-kB expression preceded by MDMA toxicity

There is an abundance of evidence showing that repeated use of 3,4-methlylenedioxymethamphetamine (MDMA; ecstasy) is associated with brain dysfunction, memory disturbance, locomotor hyperactivity, and hyperthermia. MDMA is toxic to both the serotonergic neurons and dopaminergic system. Adenosine is an endogenous purine nucleoside with a neuromodulatory function in the central nervous system. Nuclear factor kappa-B (NF-kB) plays a pivotal role in the initiation and perpetuation of an immune response by triggering the expression of major inflammatory mediators such as cytokines, chemokines, and adhesion molecules. Here, we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Male Sprague–Dawley rats were injected to MDMA (10 mg/kg) followed by intraperitoneal injection of either CGS or SCH (0.03 mg/kg each) to animals. The hippocampi were then removed for western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results show that administration of CGS following MDMA significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Taken together, these results indicate that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.     

Improving effects of long-term growth hormone treatment on monoaminergic neurotransmission and related behavioral tests in aged rats

An age-related decline in cognitive functions and physical performance has been associated with reductions in growth hormone (GH) secretion and brain neurotransmitter function. In vivo experiments were performed to study the long-term effects of exogenously administered GH on the central monoaminergic neurotransmitters serotonin, dopamine, and noradrenaline and behavioral tests in old Wistar rats. The accumulation of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in vivo. Also, the content of the neurotransmitters serotonin, dopamine, and noradrenaline and some metabolites was measured by high-pressure liquid chromatography (HPLC) in the hippocampus and striatum, brain regions involved in adult memory processing and motor coordination. The age-related decline observed in all the neurochemical parameters in control rats was significantly reversed after repeated subcutaneous administration of GH (2 mg/kg per day, 4 weeks). Thus, GH treatment exerted a long-term effect on serotonin, dopamine, and noradrenaline neurotransmission by enhancing neurotransmitter synthesis and metabolism in aged rats. The results obtained after examining working memory tasks in the eight-radial maze and motor ability in the Rotarod treadmill in aged rats were consistent with these neurochemical data; both tests were significantly improved after chronic GH treatment. Overall, these in vivo findings suggest that the positive effects induced by GH on serotonin, dopamine, and noradrenaline neurotransmitters might explain, at least in part, the effects of chronic GH treatment in improving cognitive and motor ability in aged rats, and could aid in preventing or delaying deficits in monoamines associated with learning or motor disabilities.     

<Emphasis Type="Italic">Kolaviron</Emphasis> was protective against sodium azide (NaN<Subscript>3</Subscript>) induced oxidative stress in the prefrontal cortex

Kolaviron is a phytochemical isolated from Garcina kola (G. kola); a common oral masticatory agent in Nigeria (West Africa). It is a bioflavonoid used - as an antiviral, anti-inflammatory and antioxidant - in relieving the symptoms of several diseases and infections. In this study we have evaluated the neuroprotective and regenerative effect of kolaviron in neurons of the prefrontal cortex (Pfc) before or after exposure to sodium azide (NaN₃) induced oxidative stress. Separate groups of animals were treated as follows; kolaviron (200 mg/Kg) for 21 days; kolaviron (200 mg/Kg for 21 days) followed by NaN₃ treatment (20 mg/Kg for 5 days); NaN₃ treatment (20 mg/Kg for 5 days) followed by kolaviron (200 mg/Kg for 21 days); 1 ml of corn-oil (21 days-vehicle); NaN₃ treatment (20 mg/Kg for 5 days). Exploratory activity associated with Pfc function was assessed in the open field test (OFT) following which the microscopic anatomy of the prefrontal cortex was examined in histology (Haematoxylin and Eosin) and antigen retrieval Immunohistochemistry to show astroglia activation (GFAP), neuronal metabolism (NSE), cytoskeleton (NF) and cell cycle dysregulation (p53). Subsequently, we quantified the level of Glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) in the brain tissue homogenate as a measure of stress-related glucose metabolism. Kolaviron (Kv) and Kolaviron/NaN₃ treatment caused no prominent change in astroglia density and size while NaN₃ and NaN₃/Kv induced astroglia activation and scar formation (astrogliosis) in the Pfc when compared with the control. Similarly, Kolaviron and Kv/NaN₃ did not alter NSE expression (glucose metabolism) while NaN₃ and NaN₃/Kv treatment increased cortical NSE expression; thus indicating stress related metabolism. Further studies on enzymes of glucose metabolism (G6PDH and LDH) showed that NaN₃ increased LDH while kolaviron reduced LDH in the brain tissue homogenate (P?<?0.001). In addition kolaviron treatment before (P?<?0.001) or after (P?<?0.05) NaN₃ treatment also reduced LDH expression; thus supporting its role in suppression of oxidative stress. Interestingly, NF deposition increased in the Pfc after kolaviron treatment while Kv/NaN₃ showed no significant change in NF when compared with the control. In furtherance, NaN₃ and NaN₃/Kv caused a decrease in NF deposition (degeneration). Ultimately, the protective effect of KV administered prior to NaN₃ treatment was confirmed through p53 expression; which was similar to the control. However, NaN₃ and NaN₃/Kv caused an increase in p53 expression in the Pfc neurons (cell cycle dysregulation). We conclude that kolaviron is not neurotoxic when used at 200 mg/Kg BW. Furthermore, 200 mg/Kg of kolaviron administered prior to NaN₃ treatment (Kv/NaN₃) was neuroprotective when compared with Kolaviron administered after NaN₃ treatment (NaN₃/Kv). Some of the observed effects of kolaviron administered before NaN₃ treatment includes reduction of astroglia activation, absence of astroglia scars, antioxidation (reduced NSE and LDH), prevention of neurofilament loss and cell cycle regulation.     

Chemically induced acute model of sarcosinemia in wistar rats

In the present study, we developed an acute chemically induced model of sarcosinemia in Wistar rats. Wistar rats of 7, 14 and 21 postpartum days received sarcosine intraperitoneally in doses of 0.5 mmol/Kg of body weight three time a day at intervals of 3 h. Control animals received saline solution (NaCl 0.85 g%) in the same volume (10 mL/Kg of body weight). The animals were killed after 30 min, 1, 2, 3 or 6 h after the last injection and the brain and the blood were collected for sarcosine measurement. The results showed that plasma and brain sarcosine concentrations achieved levels three to four times higher than the normal levels and decreased in a time-dependent way, achieving normal levels after 6 hours. Considering that experimental animal models are useful to investigate the pathophysiology of human disorders, our model of sarcosinemia may be useful for the research of the mechanisms of neurological dysfunction caused by high tissue sarcosine levels.     

<Emphasis Type="Italic">Satureja bachtiarica</Emphasis> ameliorate beta-amyloid induced memory impairment,oxidative stress and cholinergic deficit in animal model of Alzheimer’s disease

Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer’s disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.     

Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine

Nifedipine, a calcium channel blocker, has been reported to exert pleiotropic effects on atherosclerosis, mainly through its antioxidative properties. However, the effect of the calcium channel blocker on cognitive impairment associated with type 2 diabetes mellitus is not well known. Here, we examined the possibility that a calcium channel blocker could improve cognitive function in a type 2 diabetic mouse model, KK-A(y). KK-A(y) mice subjected to 20 trials of a passive avoidance task every week from 7 weeks of age exhibited impairment of the increase in avoidance rate and, moreover, exaggeration of its age-dependent decline, especially after 12 weeks of age. Oral administration of nifedipine at a nonhypotensive dose (0.001% in laboratory chow) to KK-A(y) mice from 10 weeks of age improved cognitive function. Nifedipine treatment decreased serum insulin level to one fifth of that in KK-A(y) mice without nifedipine. Moreover, nifedipine treatment significantly reduced superoxide anion production in the brain. Furthermore, treatment with nifedipine markedly reduced the mRNA level of Id-1, inhibitor of neural differentiation, in the brain hippocampus. We also observed the increase in blood flow in the brain in KK-A(y) mice with nifedipine treatment compared with nontreated mice. Taken together, our findings suggest that nifedipine ameliorates impaired cognitive function in type 2 diabetic mice, at least because of attenuation of hyperinsulinemia and superoxide production in the brain and possible upregulation of the neural differentiation-controlling gene, Id-1.     

The aging brain: is function dependent on growth hormone/insulin-like growth factor-1 signaling?

The role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in normal brain function is not well understood. Studies looking at cognition in humans with GH deficiency have produced controversial results. Experiments in which GH is administered to rodents have shown an apparent improvement in learning and memory. However, studies in which GH deficient or resistant mice were tested in learning and memory tasks reveal that these animals have normal cognitive performance and that their neural function does not deteriorate with age at the same rate as their normal siblings. Further research into this phenomenon revealed that these animals have elevated GH and IGF-1 expression in the hippocampus compared to normal animals. Additional studies with GH deficient and resistant mice suggested that these mutants experience a delay in age-related decline in locomotor activity and exploratory behavior. Data indicate that GH/IGF-1 deficiency and resistance do not impair neural function and instead may offer some degree of protection that results in delayed cognitive and motor aging.     

EGb761 improves the cognitive function of elderly db/db<Superscript>−/−</Superscript> diabetic mice by regulating the beclin-1 and NF-κB signaling pathways

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db^?/? mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db^?/? control, db/db^?/? 50 mg, db/db^?/? 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db^?/? mice decreased (P?<?0.05), and EGb761 could significantly improve the learning and memory function of db/db^?/? mice (P?<?0.05). EGb761 significantly improved systolic blood pressure in db/db^?/? mice (P?<?0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db^?/? group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db^?/? mice (P?<?0.05). NF-κB levels were obviously higher in the db/db^?/? group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db^?/? mice (P?<?0.05). There was a trend of increased autophagosomes in db/db^?/? mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db^?/? mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db^?/? mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.     

A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice

We developed a complex dietary supplement designed to offset five key mechanisms of aging and tested its effectiveness in ameliorating age-related cognitive decline using a visually cued Morris water maze test. All younger mice (<1 year old) learned the task well. However, older untreated mice (>1 year) were unable to learn the maze even after 5 days, indicative of strong cognitive decline at older ages. In contrast, no cognitive decline was evident in older supplemented mice, even when ～2 years old. Supplemented older mice were nearly 50% better at locating the platform than age-matched controls. Brain weights of supplemented mice were significantly greater than controls, even at younger ages. Reversal of cognitive decline in activity of complexes III and IV by supplementation was significantly associated with cognitive improvement, implicating energy supply as one possible mechanism. These results represent proof of principle that complex dietary supplements can provide powerful benefits for cognitive function and brain aging.     

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.     

Tacrine(10)-hupyridone,a dual-binding acetylcholinesterase inhibitor,potently attenuates scopolamine-induced impairments of cognition in mice

Tacrine(10)-hupyridone (A10E) was designed as a dual-binding acetylcholinesterase (AChE) inhibitor from the modification of tacrine and a fragment of huperzine A. We have found that A10E effectively inhibited AChE in a mixed competitive manner, with an IC₅₀ of 26.4 nM, which is more potent than those of tacrine and huperzine A. Most importantly, we have shown, for the first time that A10E attenuated scopolamine-induced cognitive impairments without affecting motor function in mice. A10E effectively attenuated impairments of learning and memory to a similar extent as donepezil, an inhibitor of AChE used for treating Alzheimer’s disease (AD). In addition, A10E significantly decreased AChE activity in the brain of mice, suggesting that A10E might cross the brain blood-barrier. Taken together, our results demonstrated that A10E, a designed dual-binding AChE inhibitor, could effectively reverse cognitive impairments, indicating that A10E might provide therapeutic efficacy for AD treatment.     

Age-Related Differences in Motor Imagery: Working Memory as a Mediator

Background/Study Context: Although motor imagery is a well-established phenomenon in healthy younger adults, it seems necessary to determine if older adults are still able to accurately perform imagery tasks before investigating the application of motor imagery in rehabilitation. Therefore, the purpose of this study was to determine if there is a progressive decline in motor imagery performance with age. Furthermore, we wanted to verify whether the effects of age on motor imagery were due to (or mediated by) deficits of working memory.

Methods: This study examined the key characteristics of the motor imagery ability in three groups of healthy older men and women (60–69, 70–79, and ≥80 years; mean age M = 73.8, SD = 8.3) and 40 younger subjects aged 20 to 30 years (M = 28.87, SD = 2.5). Imagery ability was measured using the Movement Imagery Questionnaire (MIQ), the Controllability of Motor Imagery (CMI) test, and two different chronometry tests. To estimate the mediational effect of working memory on age differences in the imagery measures, we employed latent variable structural equation modeling (SEM).

Results: The main findings indicated that motor imagery ability (generation, visual and kinesthetic imagery ability, controllability, and temporal organization) were better in young adults compared with older adults 70 years and older, but not in older adults 60 to 69 years of age. The analysis of the mediational effect of working memory on age differences in the motor imagery measures showed that the inclusion of working memory increased the amount of explained variance in the MIQ (ΔR ² = .03), in the CMI test (ΔR ² = .15), as well as in the mental chronometry tests (ΔR ² = .16)

Conclusion: Our findings suggest that there is potential for motor imagery to be compromised in the older age ranges, which may limit motor imagery as a rehabilitative strategy in older and in cognitively impaired individuals.     

Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer��s disease model

In light of the rising prevalence of Alzheimer’s disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might contribute to AD-related cognitive decline. Human amyloid precursor protein (hAPP) transgenic mice simulate key aspects of AD, including pathologically elevated levels of amyloid-β peptides in brain, aberrant neural network activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral abnormalities. Whether these alterations are linked in a causal chain remains unknown. To explore whether hAPP/amyloid-β–induced aberrant network activity contributes to synaptic and cognitive deficits, we treated hAPP mice with different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV) effectively reduced abnormal spike activity detected by electroencephalography. Chronic treatment with LEV also reversed hippocampal remodeling, behavioral abnormalities, synaptic dysfunction, and deficits in learning and memory in hAPP mice. Our findings support the hypothesis that aberrant network activity contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might also help ameliorate related abnormalities in people who have or are at risk for AD.     

Insulintherapie bei Kindern und Jugendlichen

Insulin therapy is the cornerstone of diabetes treatment in children and adolescents with type 1 diabetes. In most countries, insulin therapy starts in the hospital with the clinical onset of diabetes. In cases of severe dehydration and/or diabetic ketoacidosis (DKA), treatment comprises fluid and insulin replacement intravenously over a period of 12–24 h. In cases of mild dehydration, insulin treatment can be started by means of subcutaneous injections. Nowadays, intensified insulin treatment with multiple daily injections or a subcutaneous insulin infusion pump based on the basal–bolus principle represents the common therapeutic approach for children in all age groups. At the onset of the disease, daily insulin requirements are quite high, ranging between 1.5 U and 2.5 U per kilogram of body weight in patients with severe dehydration and/or DKA and 0.5–1.0 U/kg/body weight in patients with mild dehydration. In most patients, insulin needs decline some days after the start of therapy. About two-thirds of patients experience a remission phase, which is defined as a period with daily insulin requirements below 0.5 U/kg/body weight. After the end of the remission phase, insulin needs depend on the patient’s age and pubertal stage. Successful insulin treatment in childhood and adolescence requires high expertise from the patient, his or her family, and the diabetes team.     

Age-dependent effects of high fat-diet on murine left ventricles: role of palmitate

Obesity-associated heart disease results in myocardial lipid accumulation leading to lipotoxicity. However, recent studies are suggestive of protective effects of high-fat diets (HFD). To determine whether age results in differential changes in diet-induced obesity, we fed young and old (3 and 18 months) male C57Bl/6 mice control diet, low-fat diet (both 10 kcal% fat) or HFD (45 kcal% fat) for 16 weeks, after which we analyzed LV function, mitochondrial changes, and potential modifiers of myocardial structure. HFD or age did not change LV systolic function, although a mildly increased BNP was observed in all old mice. This was associated with increased myocardial collagen, triglyceride, diacylglycerol, and ceramide content as well as higher caspase 3 activation in old mice with highest levels in old HFD mice. Pyruvate-dependent respiration and mitochondrial biogenesis were reduced in all old mice and in young HFD mice. Activation of AMPK, a strong inducer of mitochondrial biogenesis, was reduced in both HFD groups and in old control or LFD mice. Cardiomyocytes from old rats demonstrated significantly reduced AMPK activation, impaired mitochondrial biogenesis, higher ceramide content, and reduced viability after palmitate (C16:0) in vitro, while no major deleterious effects were observed in young cardiomyocytes. Aged but not young cardiomyocytes were unable to respond to higher palmitate with increased fatty acid oxidation. Thus, HFD results in cardiac structural alterations and accumulation of lipid intermediates predominantly in old mice, possibly due to the inability of old cardiomyocytes to adapt to high-fatty acid load.     

Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory

The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.     

<Emphasis Type="Italic">Urtica dioica</Emphasis> modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice

Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.