Modulation of oxidative stress and apoptosis by alteration of bioactive lipids in the pancreas, and effect of zinc chelation in a rat model of Alzheimer's disease.

INTRODUCTION: Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer's disease (AD). It is known that peripheral insulin resistance in the early stages of AD precedes and is a precursor to amyloid-ß (Aß) deposition. Although it is known that improving the CNS insulin sensitivity of AD patients is an important therapeutic goal and that the majority of insulin in the brain comes from the periphery, there has been little attention to the changes that occur in the pancreatic tissue of AD patients. Therefore, it is crucial to elucidate the mechanisms affecting insulin resistance in pancreatic tissue in AD. It is known that zinc (Zn2+) chelation is effective in reducing peripheral insulin resistance, cell apoptosis, cell death, and oxidative stress. OBJECTIVE: It was aimed to determine the changes in bioactive lipids, amylin (AIPP), oxidative stress and apoptosis in pancreatic cells in the early stages of Alzheimer's disease. The main aim is to reveal the therapeutic effect of the Cyclo-Z agent on these changes seen in the pancreas due to AD disease. METHODS: AD and ADC rats were intracerebroventricular (i.c.v.) Aß1-42 oligomers. Cyclo-Z gavage was applied to ADC and SHC rats for 21 days. First of all, the effects of AIPP, bioactive ceramides, apoptosis and oxidative stress on the pancreatic tissue of AD group rats were evaluated. Then, the effect of Cyclo-Z treatment on these was examined. ELISA kit was used in biochemical analyses. RESULTS: AIPP and ceramide (CER) levels and CER/ sphingosine-1 phosphate (S1P) ratio were increased in the pancreatic tissue of AD rats. It also increased the level of CER kinase (CERK), which is known to increase the concentration of CER 1-phosphate (C1P), which is known to be toxic to cells in the presence of excessive CER concentration. Due to the increase in CER level, it was observed that apoptosis and oxidative stress increased in the pancreatic cells of AD group rats. CONCLUSION: Cyclo-Z, which has Zn2+ chelating properties, reduced AD model rats' AIPP level and oxidative stress and could prevent pancreatic apoptosis. Similar therapeutic effects were not observed in the pancreatic tissue of Cyclo-Z administered to the SH group. For this reason, it is thought that Cyclo-Z agent may have a therapeutic effect on the peripheral hyperinsulinemia observed in the early stages of AD disease and the resulting low amount of insulin transported to the brain, by protecting pancreatic cells from apoptosis and oxidative stress by regulating their bioactive metabolites.

Does Tactile Stimulation of the Face Affect the Processing of Other Faces? Neural and Behavioural Effects of Facial Touch.

The integration of vision and touch is proposed as a critical factor for processing one's own body and the bodies of others in the brain. We hypothesize that tactile stimulation on an individual's face may change the ability to process the faces of other, but not the processing of other visual images. We aimed to determine if facial touch increased the activity of the mirror system and face recognition memory of the observer. Therefore, mu suppression was measured to compare the effect of facial touch in performing two visual tasks. The participants observed faces and non-face visual images under two sets of conditions. In the first condition, a robotic finger touched the participant's cheek while in the second condition, no touch occurred. Upon each observational task, the participants were given in a recognition test. Behavioral results indicated that facial touch improved recognition performance for faces, but not for non-face visual images. Tactile stimulation increased mu suppression in both occipital and central electrodes during face processing; however, the suppression did not significantly change during non-face visual processing. Our findings support the concept that the brain uses a self-body representation, as a reference to understand the mental states or behaviors of others.

Investigation of Cyclo-Z Therapeutic Effect on Insulin Pathway in Alzheimer's Rat Model: Biochemical and Electrophysiological Parameters.

Cyclo (his-pro-CHP) plus zinc (Zn+2) (Cyclo-Z) is the only known chemical that increases the production of insulin-degrading enzyme (IDE) and decreases the number of inactive insulin fragments in cells. The aim of the present study was to systematically characterize the effects of Cyclo-Z on the insulin pathway, memory functions, and brain oscillations in the Alzheimer's disease (AD) rat model. The rat model of AD was established by bilateral injection of Aß42 oligomer (2,5nmol/10µl) into the lateral ventricles. Cyclo-Z (10mg Zn+2/kg and 0.2mg CHP/kg) gavage treatment started seven days after Aß injection and lasted for 21 days. At the end of the experimental period, memory tests and electrophysiological recordings were performed, which were followed by the biochemical analysis. Aß42 oligomers led to a significant increase in fasting blood glucose, serum insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and phospho-tau-Ser356 levels. Moreover, Aß42 oligomers caused a significant decrement in body weight, hippocampal insulin, brain insulin receptor substrate (IRS-Ser612), and glycogen synthase kinase-3 beta (GSK-3ß) levels. Also, Aß42 oligomers resulted in a significant reduction in memory. The Cyclo-Z treatment prevented the observed alterations in the ADZ group except for phospho-tau levels and attenuated the increased Aß42 oligomer levels in the ADZ group. We also found that the Aß42 oligomer decreased the left temporal spindle and delta power during ketamine anesthesia. Cyclo-Z treatment reversed the Aß42 oligomer-related alterations in the left temporal spindle power. Cyclo-Z prevents Aß oligomer-induced changes in the insulin pathway and amyloid toxicity, and may contribute to the improvement of memory deficits and neural network dynamics in this rat model.

Carnosic Acid Ameliorates Indomethacin-Induced Gastric Ulceration in Rats by Alleviating Oxidative Stress and Inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, and erosions. Carnosic acid (CA) is an important natural antioxidant found in rosemary (Rosmarinus essentials) and exhibits a protective effect by suppressing oxidative stress and inflammation. This study aimed to investigate the impact of CA on IND-induced gastric ulceration. Wistar male rats received CA (100 mg/kg) or esomeprazole (ESP) (20 mg/kg, standard drug) by oral gavage for 14 days, after that gastric ulceration was induced by oral administration of 100 mg/kg IND. CA pretreatment attenuated both gross morphological lesions and histopathological alterations. CA strongly reduced IND-induced oxidative stress, verified by a decrease in MDA (p < 0.001) and TOS levels (p < 0.05). Furthermore, an IND-dependent increase in CAT (p < 0.001) and GPx (p < 0.01) activities, as well as a reduction in GSH levels (p < 0.01), were ameliorated by CA pretreatment. CA also attenuated inflammatory damage by suppressing IL-1ß (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) production and increasing Nrf2/HO-1 (p < 0.05) expressions. In conclusion, CA shows a gastroprotective effect by reducing oxidative stress and attenuating inflammation.

Anxiolytic-like effects of extremely low frequency electric field in stressed rats: involvement of 5-HT2C receptors.

BACKGROUND: Possible modulatory effects of noninvasive brain stimulation have gained interest recently. In our study, the effect of low frequency electric fields (LF-EF) on stress-induced electrophysiological, behavioral changes and the possible involvement of serotonergic 5-HT2C receptors were investigated. MATERIALS AND METHODS: A total of eight groups including the control groups were formed by applying LF-EF with or without a 5-HT2C receptor agonist to naïve or acute stress exposed rats to demonstrate the effects of LF-EF. LF-EF administration at 10 kV/m was started 30 min before acute stress application and lasted for 1 h in total. Anxiety levels and social interaction were evaluated using the elevated plus maze test and social interaction test, respectively. Auditory evoked potentials (AEP) were recorded by using ascending loudness paradigms. Loudness dependence AEP (LDAEP) was calculated by using amplitude values to analyze serotonergic transmission. Serotonin and glucocorticoid levels were measured in the frontal cortex and hippocampus. RESULTS: It was observed that the applied LF-EF reduced the anxiety behavior, and attenuated the LDAEP responses in stress and/or 5-HT2C receptor agonist applied groups. In parallel, an increase in serotonin levels and a decrease in glucocorticoid levels were observed. However, LF-EF exposure was ineffective in impaired social interaction. CONCLUSIONS: Our findings show that 10 kV/m LF-EF administration may modulate the neural network and physiological responses associated with mild acute stress. 5-HT2C receptor dependent functions are thought to play a role in the anxiolytic effect of LF-EF.

Cognitive dysfunctions and spontaneous EEG alterations induced by hippocampal amyloid pathology in rats.

PURPOSE: We aimed to determine the effects of different doses of amyloid-beta (Aß) peptide on learning and memory, and whether the changes in brain oscillations induced by dose-dependent accumulation of Aß could be used as biomarkers to detect early stages of Alzheimer's disease (AD). MATERIAL AND METHODS: Male albino Wistar rats aged 3 months were randomly divided into four groups (n â€‹= â€‹12/group) obtained by i. h. Injection (to the dorsal hippocampus) of saline or different doses of 0.01 â€‹µg/µl, 0.1 â€‹µg/µl, and 1 â€‹µg/µl of Aß. After two weeks of recovery period, open field and novel object recognition tests were performed and spontaneous EEG recordings were obtained. Later, hippocampus tissues were collected for Western blot and ELISA analysis. RESULTS: A significant decrement in recognition memory was observed in 0.1 â€‹µg/µl, and 1 â€‹µg/µl injected groups. In addition, Aß accumulation induced significant decrement of the expression of NeuN, SNAP-25, SYP, and PSD-95 proteins, and led to the increment of GFAP expression in hippocampus. Moreover, we detected remarkable alterations in spontaneous brain activity. The hippocampal Aß levels were negatively correlated with hippocampal gamma power and positively correlated with hippocampal theta power. Also, we observed significant changes in coherence values, indicating the functional connectivity between different brain regions, after the accumulation of Aß. Especially, there was a significant correlation between changes in frontohippocampal theta coherence and in frontotemporal theta coherence. CONCLUSIONS: Our findings indicate that Aß peptide induces AD-like molecular changes at certain doses, and these changes could be detected by evaluating brain oscillations.

The Role of Acetylcholine on the Effects of Different Doses of Sulfite in Learning and Memory.

In this study, the effects of different doses of sulfite on learning, memory, and long term potentiation as well as the relationship of these effects with acetylcholine pathways, Arc and synapsin 1 levels were investigated. Sixty male Wistar albino rats were randomly divided into three groups as control, S100, and S260. Sodiummetabisulfite (S100;100 mg/kg/day, S260;260 mg/kg/day) was given by oral administration. Behavioral changes were evaluated. After long term potentiation recordings from the perforant pathway-dentate gyrus synapses, animals were sacrificed. Acetylcholinesterase activity, choline acetyltransferase activity, acetylcholine level as well as Arc and Synapsin 1 expressions were analyzed on the hippocampi. The total distance and average velocity values in the open field and Morris water maze tests increased in the sulfite groups, while the discrimination index in the novel object recognition test decreased compared to controls. Acetylcholine levels and choline acetyltransferase activity were also increased in the sulfite groups, while acetylcholinesterase activity was decreased compared to controls. Sulfite intake attenuated long term potentiation in the hippocampus. It has been observed that the excitatory postsynaptic potential slope and population spike amplitude of the field potentials obtained in sulfite groups decreased. This impairment was accompanied by a decrease in Arc and synapsin 1 expressions. In conclusion, it has been shown that sulfite intake in adults impairs learning and memory, possibly mediated by the cholinergic pathway. It is considered that the decrement in Arc and synapsin expressions may play a role in the mechanism underlying the impairment in long term potentiation caused by toxicity.

Effects of thymoquinone on scopolamine-induced spatial and echoic memory changes through regulation of lipid peroxidation and cholinergic impairment.

Thymoquinone (TMQ), one of the main components active of Nigella sativa, shows very useful biomedical properties. Evidence suggests that cholinergic dysfunction and oxidative stress play role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In the present study, we investigated the anti-amnestic effect of TMQ in scopolamine-induced animal model of AD. Wistar rats were randomly divided into four groups; Sham(SH), TMQ-treated(TMQ), scopolamine-treated(SCO) and scopolamine+TMQ-treated(SCO_TMQ) groups. TMQ (20 mg/kg) prepared in corn oil was administered intraperitoneally (i.p.) 1-h before experiments. Scopolamine (1 mg/kg) dissolved in 0.9% physiological saline was administered intraperitoneally (i.p.). We recorded mismatch negativity (MMN) response as an electrophysiological correlate of echoic memory. Object location memory (OLM) and Y-maze alternation tests were carried out to assess spatial memory. Then, the brain homogenates content of thiobarbituric-acid-reactive-substances (TBARS), 4-Hydroxy-2-nonenal (4-HNE) and acetylcholine (ACh)/acetylcholine (AChE) activity were biochemically determined. In the scopolamine-treated rats, TMQ was found to significantly improve the discrimination and spontaneous alteration levels in the OLM and Y-maze tests, respectively. Furthermore, TMQ significantly mitigated the scopolamine-induced attenuation of MMN and related theta responses. Moreover, scopolamine treatment increased TBARS/4-HNE level and decreased ACh level in the brain, and TMQ was able to significantly prevent these effects. AChE activity was increased in the SCO group; this effect was significantly attenuated by TMQ. TMQ diminished the lipid peroxidation and cholinergic dysfunction in the scopolamine-induced AD rat model which all reflected in improving the MMN/theta response and spatial memory. This may implement TMQ as an adjuvant therapeutic strategy in ameliorating AD.

The effects of acute and chronic exposure to 900 MHz radiofrequency radiation on auditory brainstem response in adult rats.

The aim of this study was to determine the effects of short and long-term RFR exposure on ABR by evaluating lipid peroxidation and antioxidant status in adult rats. Sixty male albino Wistar rats were randomly divided into four groups. S1:1 week sham, S10:10 weeks sham, E1:1 week RFR, E10:10 weeks RFR. Experimental group rats were exposed to RFR 2 h/day, 5 days/week during the test period. Sham rats were kept in the same conditions without RFR. After the experiment, ABRs were recorded from the mastoids of rats using tone burst acoustic stimuli. Biochemical investigations in rat brain and ultrastructural analysis in temporal cortex were performed. ABR wave I latency prolonged in E1-group and shortened in E10-group compared to their shams. TBARS level increased in E1-group, decreased in E10-group, on the contrary, SOD and CAT activities and GSH level decreased in E1-group, increased in E10-group compared to their sham groups. Edema was present in the neuron and astrocyte cytoplasms and astrocyte end-feet in both E1 and E10 groups. Our results suggest that 900 MHz RFR may have negative effects on the auditory system in acute exposure and no adverse effects in chronic exposure without weekends.