Exercise training and high-fat diet elicit endocannabinoid system modifications in the rat hypothalamus and hippocampus

The purpose of the present study was to examine the effect of chronic exercise on the hypothalamus and hippocampus levels of the endocannabinoids (eCBs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and of two AEA congeners and on the expression of genes coding for CB1, CB2 receptors (Cnr1 and Cnr2, respectively), and the enzymes responsible for eCB biosynthesis and degradation, in rats fed with a standard or high-fat diet. Male Wistar rats (n = 28) were placed on a 12-week high-fat (HFD) or standard diet period, followed by 12 weeks of exercise training for half of each group. Tissue levels of eCBs and related lipids were measured by liquid chromatography mass spectrometry, and expression of genes coding for CB1 and CB2 receptors and eCB metabolic enzymes was measured by quantitative real-time polymerase chain reaction (qPCR). HFD induced a significant increase in 2-AG (p < 0.01) in hypothalamus. High-fat diet paired with exercise training had no effect on AEA, 2-AG, and AEA congener levels in the hypothalamus and hippocampus. Cnr1 expression levels were significantly increased in the hippocampus in response to HFD, exercise, and the combination of both (p < 0.05). Our results indicate that eCB signaling in the CNS is sensitive to diet and/or exercise.     

Beneficial effects of hydro-alcoholic extract of Caralluma fimbriata against high-fat diet-induced insulin resistance and oxidative stress in Wistar male rats

The main aim of this study was to investigate the beneficial effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) on the effects of high-fat diet feeding on insulin resistance and oxidative stress in Wistar rats. High-fat diet (60 % of fat) and CFE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 90 days. Feeding with high-fat diet resulted in the development of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia and impaired insulin sensitivity (P?<?0.05). Administration of CFE to high-fat diet-fed rats for 90 days resulted in a significant improvement in plasma glucose, insulin, leptin, and triglycerides. Regarding liver antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation and lower GSH levels and lower activities of enzymatic antioxidants, while CFE treatment prevented all these observed abnormalities. In conclusion, intake of CFE may be beneficial for the suppression of high-fat diet-induced insulin resistance and oxidative stress.     

Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis

Diet-associated insulin resistance (IR) is intimately correlated with the progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has been applied to enhance insulin sensitivity. With limited permeability to blood-brain-barrier, it is unclear that whether oral PIO available to cure both the peripheral IR and the impairment in the hippocampus. We evaluated the levels of peripheral and hippocampal IR via the homeostatic model assessment of insulin resistance and hippocampal IRS-1/Akt phosphorylation, respectively, of Wistar Kyoto rats fed with a regular chew or high fructose diet (HFD) for 12 weeks. Gavage with PIO (30 mg/kg/day, 2 weeks) significantly reduced the peripheral IR and reversed the level of hippocampal PPARγ. Moreover, HFD-activated microglia and astrocyte were effectively relieved by PIO. The suppressed brain-derived neurotrophic factor, CaMKIIα, and postsynaptic density protein 95 in the hippocampus were effectively reversed by PIO. However, the hippocampal IR and inhibition of adult neurogenesis in dentate gyrus were not restored by PIO. Together, PIO oral application may reverse the HFD-induced peripheral IR and maintain the existed neuronal circuit by ameliorating glial activation and enhancing synaptic density through BDNF but failed to restore adult neurogenesis in the hippocampus.     

Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone

AimChronic consumption of a high-fat (HF) diet contributes to peripheral insulin resistance and elevated plasma corticosterone. However, the effect of HF consumption on the neurofunctional insulin receptors and neuronal corticosterone level is unclear. We tested the hypothesis that HF consumption can lead to peripheral insulin resistance, elevated neuronal corticosterone, and impaired neuronal responses to insulin.Main methodsMale Wistar rats were fed with normal diet or HF diet for 4, 8 or 12 weeks. At the end of each dietary period, plasma was collected for investigating peripheral insulin resistance parameters and corticosterone. Brains were then rapidly removed for studying the function of neuronal insulin receptors (IRs) by extracellular recording in CA1 hippocampus, neuronal IR signaling by immunoblot technique and neuronal corticosterone.Key findingsElevated plasma corticosterone level was initially seen in 4-week HF-fed rats. Peripheral insulin resistance developed at 8-week HF-fed rats. However, the elevated neuronal corticosterone level was found at 12-week HF consumption. The neuronal IR response demonstrated by insulin-mediated long-term depression in CA1 hippocampus was diminished in 12-week HF-fed rats. The phosphorylation levels of neuronal IR, IR substrate 1 and Akt/PKB were decreased in 12-week HF-fed rats with no change in these proteins. There was a correlation among peripheral insulin resistance, neuronal stress (elevated neuronal corticosterone), and neuronal insulin resistance in HF group.SignificanceOur findings suggest that HF consumption can lead to the elevation of corticosterone and peripheral insulin resistance, which could contribute to neuronal insulin resistance and neuronal stress.     

High intake of chicken and pork proteins aggravates high-fat-diet-induced inflammation and disorder of hippocampal glutamatergic system

High-fat diets have been associated with neurodegenerative diseases, which are also largely related to the type and amount of dietary proteins. However, to our knowledge, it is little known how dietary proteins affect neurodegenerative changes. In this study, we investigated the effects of dietary proteins in a high-fat diet on hippocampus functions related to enteric glial cells (EGCs) in Wistar rats that were fed either 40% or 20% (calorie) casein, chicken protein or pork protein for 12 weeks (n=10 each group). Inflammatory factors, glutamatergic system, EGCs, astrocytes and nutrient transporters were measured. A high-chicken-protein diet significantly increased the levels of systemic inflammatory factors, Tau protein and amyloid precursor protein mRNA level in the rat hippocampus. The type and level of dietary proteins in high-fat diets did not affect the gene expression of glial fibrillary acidic protein and α-synuclein (P>.05), indicating a negligible effect on astrocyte activity. However, the high-protein diets up-regulated glutamate transporters compared with the low-protein diets (P<.05), while they reduced the γ-aminobutyric acid content in high-chicken and -pork-protein diets (P<.05). Thus, compared with a low-protein diet (20%), a high-chicken or -pork-protein diet (40%) under a high-fat background could alter the balance between glutamatergic system and neurotransmitter and have a stronger effect on the interactions between hippocampal glutamatergic system and EGCs.     

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 (27 months old) were fed daily with standard chow supplemented with 1 ppm of diphenyl diselenide and subjected to swimming training with a workload (1% of body weight, 20 min/day) for 4 weeks. 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.     

The Effect of Short-Term Feeding of a High-Coconut Oil or High-Fat Diet on Neuroinflammation and the Performance of an Object–Place Task in Rats

The consumption of high-fat and high-sugar diets, in the form of junk food, and binge eating are now common. Increasing evidence suggests that a high-fat diet (HFD) can induce neuroinflammation and alter behavior. I aimed to study the effects of diets of differing fat content on neuroinflammation and spatial memory using an object–place (OP) task. Thirty-two adult male rats were allocated to four groups and fed a regular diet (Regular diet), a control diet (Control diet), an HFD (60% of calories from lard), or a high-coconut oil diet (HCOD; 60% of calories from coconut oil) for 3 days. Their water intake, food consumption, body mass, and metabolic variables were measured. HFD-fed rats showed significantly poorer performance on the OP task, as assessed using the discrimination index (??0.208?±?0.094), than the Regular (0.462?±?0.078; P?<?0.0001) and Control (0.379?±?0.081; P?=?0.0003) groups. However, no significant difference was observed in spatial memory between the HCOD and Regular groups. The concentrations of neuroinflammatory markers (interleukin [IL]-1β, IL-6, tumor necrosis factor α, and nuclear factor κB) were also measured in the hippocampus and prefrontal cortex. HFD-fed rats showed significantly higher levels of neuroinflammatory markers than the Regular and Control diet-fed groups. HCOD feeding did not induce neuroinflammation in the hippocampus and prefrontal cortex compared with the Regular and Control groups.

     

High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes

Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in developed and developing nations and over 50 % of patients with prolonged stages of disease experience forms of autonomic neuropathy. These patients have symptoms indicating disrupted enteric nervous system function including gastric discomfort, gastroparesis and intestinal dysmotility. Previous assessments have examined enteric neuronal injury within either type 1 diabetic or transgenic type 2 diabetic context. This study aims to assess damage to myenteric neurons within the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2 diabetes, as this disease context is most parallel to the human condition and disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After 8 weeks, the total number of duodenal myenteric neurons and the synaptophysin density index were reduced and transmission electron microscopy showed axonal swelling and loss of neurofilaments and microtubules, suggesting compromised neuronal health. High-fat diet ingestion correlated with a loss of neurons expressing VIP and nNOS but did not affect the expression of ChAT, substance P, calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those with inhibitory nature. This pathology may underlie dysmotility and other negative GI symptoms experienced by human type 2 diabetic and obese patients.     

Supplementary Chromium(III) Propionate Complex Does Not Protect Against Insulin Resistance in High-Fat-Fed Rats

Improper eating habits such as high-fat or high-carbohydrate diets are responsible for metabolic changes resulting in impaired glucose tolerance, hyperinsulinemia, insulin resistance, and ultimately diabetes. Although the essentiality of trivalent chromium for humans has been recently questioned by researchers, pharmacological dosages of this element can improve insulin sensitivity in experimental animals and diabetic subjects. The aim of the study was to assess the preventive potential of the supplementary chromium(III) propionate complex (CrProp) in rats fed a high-fat diet. The experiment was conducted on 32 male Wistar rats divided into four groups and fed the following diets: the control (C, AIN-93G), high-fat diets (HF, 40 % energy from fat), and a high-fat diet supplemented with CrProp at dosages of 10 and 50 mg Cr/kg diet (HF?+?Cr10 and HF?+?Cr50, respectively). After 8 weeks, high-fat feeding led to an increased body mass, hyperinsulinemia, insulin resistance, a decreased serum urea concentration, accumulation of lipid droplets in hepatocytes, and increased renal Fe and splenic Cu contents. Supplementary CrProp in both dosages did not alleviate these changes but increased renal Cr content and normalized splenic Cu content in high-fat-fed rats. Supplementary CrProp does not prevent the development of insulin resistance in rats fed a high-fat diet.     

Damage to Neurons and Oligodendrocytes in the Hippocampal CA1 Sector after Transient Focal Ischemia in Rats

Focal brain lesions such as transient focal cerebral ischemia can lead to neuronal damage in remote areas, including the ipsilateral substantia nigra and hippocampus, as well as in the ischemic core. In this study, we investigated acute changes in the ipsilateral hippocampus from 1 up to 7 days after 90 min of transient focal cerebral ischemia in rats, using anti-NeuN (neuronal nuclei), anti-Cu/Zn-superoxide dismutase (Cu/Zn-SOD), anti-Mn-SOD, anti-neuronal nitric oxide synthase (nNOS), anti-inducible NOS (iNOS), anti-glial fibrillary acidic protein (GFAP), anti-ionized calcium-binding adaptor molecule 1(Iba 1) and anti-2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) antibodies. In our western blot and histochemical analyses, present results show that transient focal cerebral ischemia in rats can cause a severe and acute damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector. The present findings also demonstrate that the expression of iNOS produced by Iba 1-immunopositive microglia precedes the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia. In contrast, our results suggest that increased reactive oxygen species (ROS) production during reperfusion cannot lead to damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Our double-labeled immunohistochemical study demonstrates that the overexpression of iNOS produced by Iba 1-immunopositive microglia may play a pivotal role in the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector at an acute stage after transient focal cerebral ischemia.     

Changes in cardiac Na<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase expression and activity in female rats fed a high-fat diet

The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na⁺/K⁺-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150–200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the α₁ subunit of Na⁺/K⁺-ATPase by 30% (p < 0.05), expression of total α₁ subunit of Na⁺/K⁺-ATPase by 31% (p < 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p < 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p < 0.01) and 62% (p < 0.05), respectively. Our results suggest that a HF diet alters cardiac Na⁺/K⁺-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats.     

Biochemical, Histological, and Memory Impairment Effects of Chronic Copper Toxicity: A Model for Non-Wilsonian Brain Copper Toxicosis in Wistar Rat

Animal models of copper toxicosis rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper and zinc levels in the liver and hippocampus, on biochemical parameters, and on neurobehavioral functions (by Morris water maze) of male Wistar rats. Copper-administered animals exhibited significantly decreased serum acetylcholinesterase (AChE) activity and impaired neuromuscular coordination and spatial memory compared to control rats. Copper-intoxicated rats showed significant increase in liver and hippocampus copper content (99.1 and 73 % increase, respectively), 40.7 % reduction in hepatic zinc content, and interestingly, 77.1 % increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive grade 4 copper depositions and grade 1 copper-associated protein in hepatocytes of copper-intoxicated rats were substantiated by rhodanine and orcein stains, respectively. Copper-intoxicated rats demonstrated swelling and increase in the number of astrocytes and copper deposition in the choroid plexus, with degenerated neurons showing pyknotic nuclei and dense eosinophilic cytoplasm. In conclusion, the present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory and neuromuscular coordination, swelling of astrocytes, decreased serum AChE activity, copper deposition in the choroid plexus, neuronal degeneration, and augmented levels of copper and zinc in the hippocampus of male Wistar rats.     

Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy

Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT₁ receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT₁ receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT₁ receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT₁ receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT₁ receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy.     

Calpain I Activity and Its Relationship with Hippocampal Neuronal Death in Pilocarpine-Induced Status Epilepticus Rat Model

This study aims to establish pilocarpine-induced rat model of status epilepticus (SE), observe the activity of calpain I in the rat hippocampus and the subsequent neuronal death, and explore the relationship between calpain I activity and neuronal death in the hippocampus. Fifty-eight adult male Wistar rats were assigned randomly into either control group (n = 8) or epilepsy group (n = 50). SE was induced in the epilepsy group using pilocarpine. Before the injection, the rats were given atropine sulfate to reduce the side effect of pilocarpine. All rats in the seizure group were grouped into either SE or non-SE, depending on whether they developed convulsive seizures. The rats in SE group were treated with chloral hydrate to stop seizures after 60 min. Control animals were treated with the same dose of 0.9 % saline. All rats were monitored for seizures. At 24 h after SE, the rats’ left brain tissues were stained by HE and TUNEL. Neuronal necrosis and apoptosis in the hippocampal CA3 area were observed. Calpain I activity in the right hippocampus was also observed using western blotting. Eighty percent of the rats in the seizure group developed SE, of which 35 % died. No rat died in both the control and non-SE groups. At 24 h after SE, the number of HE-stained neurons decreased (SE group: 55.19 ± 8.23; control group: 102.13 ± 3.73; non-SE group: 101.2 ± 2.86) and the number of TUNEL-positive neurons increased (SE group: 4.91 ± 1.35; non-SE and control group: 0). No obvious changes were observed in the neurons of the control and non-SE group animals. The 76 kDa cleavage of calpain I (the average optical density ratio is 0.096 ± 0.015) emerged in the SE group. Neuronal death has a direct relationship with calpain I activity. There is high success rate and lower death rate for pilocarpine to induce SE. At 24 h after SE, activity of calpain I, neuronal necrosis and apoptosis increased in the hippocampus. Neuronal death has a direct relationship with calpain I activity, which suggests that calpain I plays an important role in neuronal damage during SE.     

Increased expression of HIF-1alpha, nNOS, and VEGF in the cerebral cortex of anemic rats

This study tested the hypothesis that specific hypoxic molecules, including hypoxia-inducible factor-1alpha (HIF-1alpha), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF), are upregulated within the cerebral cortex of acutely anemic rats. Isoflurane-anesthetized rats underwent acute hemodilution by exchanging 50% of their blood volume with pentastarch. Following hemodilution, mean arterial pressure and arterial Pa(O(2)) values did not differ between control and anemic rats while the hemoglobin concentration decreased to 57 +/- 2 g/l. In anemic rats, cerebral cortical HIF-1alpha protein levels were increased, relative to controls (1.7 +/- 0.5-fold, P < 0.05). This increase was associated with an increase in mRNA levels for VEGF, erythropoietin, CXCR4, iNOS, and nNOS (P < 0.05 for all), but not endothelial NOS. Cerebral cortical nNOS and VEGF protein levels were increased in anemic rats, relative to controls (2.0 +/- 0.2- and 1.5 +/- 0.4-fold, respectively, P < 0.05 for both). Immunohistochemistry demonstrated increased HIF-1alpha and VEGF staining in perivascular regions of the anemic cerebral cortex and an increase in the number of nNOS-positive cerebral cortical cells (3.2 +/- 1.0-fold, P < 0.001). The nNOS-positive cells costained with the neuronal marker, Neu-N, but not with the astrocytic marker glial fibrillary acidic protein (GFAP). These nNOS-positive neurons frequently sent axonal projections toward cerebral blood vessels. Conversely, VEGF immunostaining colocalized with both neuronal (NeuN) and astrocytic markers (GFAP). In conclusion, acute normotensive, normoxemic hemodilution increased the levels of HIF-1alpha protein and mRNA for HIF-1-responsive molecules. nNOS and VEGF protein levels were also increased within the cerebral cortex of anemic rats at clinically relevant hemoglobin concentrations.     

Differential Effects of Low- and High-dose Zinc Supplementation on Synaptic Plasticity and Neurogenesis in the Hippocampus of Control and High-fat Diet-fed Mice

In the present study, we investigated the concentration-dependent effect of zinc (Zn) supplementation on the adult hippocampus in a high-fat diet (HFD)-fed obese mouse model. Four-weeks after HFD- and control diet (CD)-feeding, mice were provided with low (15 ppm) or high (60 ppm) doses of Zn in their drinking water for additional 4 more weeks along with their respective diets. Compared to the CD-fed mice, HFD-feeding elicited the reduction of neurogenic markers such as nestin, Ki67, doublecortin (DCX), and 5-bromo-2′-deoxyuridine (BrdU) in the dentate gyrus. Additionally, HFD-feeding reduced the levels of synaptic markers (synaptophysin and N-methyl-d-aspartate receptor) and brain-derived neurotrophic factor (BDNF), while lipid peroxidation was significantly increased in the hippocampus of HFD-fed mice. Against detrimental effects of high-dose Zn, low-dose Zn supplementation in CD-fed mice did not yield any remarkable changes in these parameters. Interestingly, administration of low doses of Zn to HFD-induced obese mice prominently ameliorated HFD-induced changes in neurogenic, synaptic plasticity markers and BDNF levels as well as lipid peroxidation in the hippocampus. In contrast, high-dose Zn supplementation in HFD-fed mice exacerbated the reduction of markers for neurogenesis and synaptic plasticity as well as BDNF levels, but not 4-HNE levels, in the hippocampus. These results suggest that low-dose Zn supplementation in obese mice could reverse the HFD-induced reduction in neurogenic and synaptic marker proteins in the hippocampus by reducing lipid peroxidation and improving BDNF expression, while high-dose Zn supplementation exacerbates the reduction of neurogenesis by affecting synaptic markers and BDNF levels in the hippocampus.     

The effects of oral taurine administration on behavior and hippocampal signal transduction in rats

Taurine, 2-aminoethylsulfonic acid, is one of the most abundant amino acids in the brain. It has various important physiological functions as a neuromodulator and antioxidant. Taurine is expected to be involved in depression; however, knowledge regarding its function in relation to depression is limited. In this study, we attempted to elucidate the effects of oral taurine administration on antidepressant-like behaviors in rats and depression-related signal transduction in the hippocampus. In behavioral tests, rats fed a high taurine (HT: 45.0 mmol/kg taurine) diet for 4 weeks (HT4w) showed decreased immobility in the forced swim test (FS) compared to controls. However, rats fed a low taurine (LT: 22.5 mmol/kg taurine) diet for 4 weeks or an HT diet for 2 weeks (HT2w) did not show a significant difference in FS compared to controls. In biochemical analyses, the expression of glutamic acid decarboxylase (GAD) 65 and GAD67 in the hippocampus was not affected by taurine administration. However, the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2), protein kinase B (Akt), glycogen synthase kinase3 beta (GSK3β) and cAMP response element-binding protein (CREB) were increased in the hippocampus of HT4w and HT2w rats. Phospho-calcium/calmodulin-dependent protein kinase II (CaMKII) was increased in the hippocampus of HT4w rats only. Moreover, no significant changes in these molecules were observed in the hippocampus of rats fed an HT diet for 1 day. In conclusion, our findings suggest that taurine has an antidepressant-like effect and an ability to change depression-related signaling cascades in the hippocampus.     

Hypercaloric diet and chronic stress desynchronizes the temporal pattern of rats’ insulin release

This study evaluated the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of biochemical and hormonal markers. Obesity model was achieved by hypercaloric diet exposure. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress + standard chow (S), and stress + hypercaloric diet (SHD) and analysed at three time points: ZT0, ZT12 and ZT18. Chronic stress was performed 1 h/per day, 5 days/per week, during 80 days. The presence of temporal pattern in naïve animals’ insulin release was accomplished. Hypercaloric diet induced obesity, increasing rats’ insulin and glucose levels; while chronic stress reduced insulin levels. There were interactions between chronic stress and obesity in serum insulin and glucose levels; and between time points and obesity in insulin levels. In conclusion, long exposure to hypercaloric diet and chronic stress were able to desynchronize temporal pattern of insulin release, contributing to the pathophysiology of obesity and its complications.     

Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats

The drastic increase in the consumption of fructose encouraged the research to focus on its effects on brain physio-pathology. Although young and adults differ largely by their metabolic and physiological profiles, most of the previous studies investigated brain disturbances induced by long-term fructose feeding in adults. Therefore, we investigated whether a short-term consumption of fructose (2 weeks) produces early increase in specific markers of inflammation and oxidative stress in the hippocampus of young and adult rats. After the high-fructose diet, plasma lipopolysaccharide and tumour necrosis factor (TNF)-alpha were found significantly increased in parallel with hippocampus inflammation, evidenced by a significant rise in TNF-alpha and glial fibrillar acidic protein concentrations in both the young and adult groups. The fructose-induced inflammatory condition was associated with brain oxidative stress, as increased levels of lipid peroxidation and nitro-tyrosine were detected in the hippocampus. The degree of activation of the protein kinase B, extracellular signal-regulated kinase 1/2, and insulin receptor substrate 1 pathways found in the hippocampus after fructose feeding indicates that the detrimental effects of the fructose-rich diet might largely depend on age. Mitochondrial function in the hippocampus, together with peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, was found significantly decreased in fructose-treated adult rats. In vitro studies with BV-2 microglial cells confirmed that fructose treatment induces TNF-alpha production as well as oxidative stress. In conclusion, these results suggest that unbalanced diet, rich in fructose, may be highly deleterious in young people as in adults and must be strongly discouraged for the prevention of diet-associated neuroinflammation and neurological diseases.     

Bradykinin Postconditioning Protects Pyramidal CA1 Neurons Against Delayed Neuronal Death in Rat Hippocampus

Aims The present study was undertaken to evaluate possible neuroprotective effect of bradykinin against delayed neuronal death in hippocampal CA1 neurons if applied two days after transient forebrain ischemia in the rat. Methods Transient forebrain ischemia was induced in male Wistar rats by four-vessel occlusion for 8 min. To assess efficacy of bradykinin as a new stressor for delayed postconditioning we used two experimental groups of animals: ischemia 8 min and 3 days of survival, and ischemia 8 min and 3 days of survival with i.p. injection of bradykinin (150 μg/kg) applied 48 h after ischemia. Results We found extensive neuronal degeneration in the CA1 region at day 3 after ischemia/reperfusion. The postischemic neurodegeneration was preceded by increased activity of mitochondrial enzyme MnSOD in cytoplasm, indicating release of MnSOD from mitochondria in the process of delayed neuronal death. Increased cytosolic cytochrome c and subsequently caspase-3 activation are additional signs of neuronal death via the mitochondrial pathway. Bradykinin administration significantly attenuated ischemia-induced neuronal death, and also suppressed the release of MnSOD, and cytochrome c, and prevented caspase-3 activation. Conclusions Bradykinin can be used as an effective stressor able to prevent mitochondrial failure leading to apoptosis-like delayed neuronal death in postischemic rat hippocampus.