Cem Süer

Blood pressure relationship to nitric oxide, lipid peroxidation, renal function, and renal blood flow in rats exposed to low lead levels.

The results of experiments designed to show that inhibition of nitric oxide production in rats exposed to low lead levels increases vascular resistance, decreases renal blood flow and glomerular function, and enhances oxidative stress. Forty-five adult male Sprague-Dawley rats were divided into four groups. Group A was used as controls and consisted of rats that received no treatment; group B acted as NO-inhibited controls by receiving l-NAME (NG-nitro-l-arginine methyl ester) as the NO inhibitor; group C was injected intraperitoneally with 8 mg/kg lead acetate for 2 wk; and group D receiving lead acetate plus l-NAME.Compared to healthy controls, significant elevation of the mean (p<0.01), systolic (p<0.04), and diastolic (p<0.01) blood pressures was found in the lead-treated rats. The renal blood flow was 1550±468 blood per unit (bpu) in the controls, 488±220 bpu in the l-NAME controls, 1050±458 bpu in the lead-treated group, and 878±487 bpu in the Pb plus l-NAME group.Low-level lead exposure did not change the urinary flow rate, creatinine clearance, and the creatinine, potassium, phosphorus, glucose, and protein excretion in 24-h urine. In the lead plus NO-inhibited rats, a significant decrease in sodium ion excretion was observed (p<0.01). The NO levels of the lead exposed, l-NAME-treated controls, and l-NAME plus lead-exposed groups are significantly lower compared to untreated control:: p<0.002, p<0.001, and p<0.01, respectively. When compared to untreated controls, the plasma malondialdehyde levels were not significantly different in the lead exposed, lead plus l-NAME, and l-NAME control groups.These results suggest that lead-induced hypertension might be related to a decrease of NO and consequent vasoconstriction, rather than to a decrease of renal blood flow or to decreases in renal sodium.

The effects of long-term sleep deprivation on the long-term potentiation in the dentate gyrus and brain oxidation status in rats

Some evidence suggests that sleep deprivation might impair synaptic plasticity and produce oxidative stress in the hippocampus. However it is not clear whether impairment of long-term potentiation depends on the oxidative stress evoked by sleep deprivation protocol. In this study we aimed to investigate the effects of a 21-day sleep deprivation period on long-term plasticity taking into account the stressful effect of sleep deprivation. Sleep deprivation was carried out using the multiple platforms method on adult male Wistar rats. Long-term potentiation was studied in the medial perforant pathway-dentate gyrus synapses. Elevated T test was applied, and blood corticosterone levels were measured. Lipid peroxidation products in whole brain and hippocampus were determined. No significant difference was found between the sleep deprived, pedestal and cage control groups at the end of the 21-day period when corticosterone levels were compared. The results of the elevated T test indicated that sleep deprivation did not change the anxiety-like behavior of the animals. When compared with cage or pedestal control groups, sleep deprived rats displayed elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities together with impaired long-term potentiation maintenance. It can be argued that 21-day SD may impair the maintenance of long-term potentiation evoked in the dentate gyrus, and the balance between oxidant and antioxidant defenses of the hippocampus.

Effects of cigarette smoking on cognitive processing

Several previous studies have reported that cigarette smoking enhances performance of cognitive processing. These enhancements are generally attributed to the pharmacological effects of nicotine, while there is some debate whether the effects of smoking/nicotine are a result of recovery from abstinence. Evoked potentials (EPs) and event related potentials (ERPs) of the brain have been applied as an index of information processing in a wide variety of normal and cognitive impaired subjects. This study was carried out on 20 healthy students (23 ± 2.3 years old) from the medical faculty of City University. Study population comprised ten chronic cigarette smokers consuming an average of 14 ± 4.2 cigarettes per day, with a history of smoking for more than one year. Ten non--smokers served as control. Standard oddball paradigm was presented, and EEG activity was recorded at the Fz, Cz, Pz electrode sites. Twenty responses to target stimuli were averaged at each location. N1, P2, N2, and P300 components were evaluated in these recordings. Amplitudes were measured relative to prestimulus baseline, and peak latencies were defined as the time point of maximum amplitude. It was found that there were no significant differences between either N1, P2, N2, P300 amplitudes or peak latency values of cigarette smokers and non smokers. As a result, chronic cigarette smoking generally does not improve cognitive processing

Evaluation of cognitive performance by using P300 auditory event related potentials (ERPs) in patients with growth hormone (GH) deficiency and acromegaly

CONTEXT Impaired cognitive performance has been demonstrated in adults with GH deficiency and acromegaly by using different neuropsychological tests. P300 event related potential (ERP) application is a well established neurophysiological approach in the assessment of cognitive performance. OBJECTIVES Evaluation of cognitive performance by using P300 ERPs has not been reported in acromegaly, and the comparisons of the P300 ERPs between the patients with GH deficiency and GH excess have not been done yet. Therefore present study was designed to investigate the effects of GH deficiency and GH excess on cognitive performance by using P300 ERPs. DESIGN AND METHODS The study comprised 19 patients with severe GH deficiency, 18 acromegalic patients and 16 age, education and sex matched healthy controls. Baseline auditory ERPs were obtained at Fz (frontal), Cz (central), Pz (parietal) and Oz (occipital) electrode sites in GH deficient group, GH excess group and control group. RESULTS There was a significant difference between mean serum IGF-I levels in the GH deficient and acromegalic patients (48+/-38 ng/ml and 742+/-272 ng/ml, respectively) (P=0.01). The mean P300 latency of the patients with GH deficiency was significantly (P=0.0001) prolonged when compared with that of normal controls and acromegalic patients at all electrode sites. The mean P300 amplitude of the patients with acromegaly was significantly (P=0.005) lower when compared with that of normal controls and GH deficient patients at all electrode sites. CONCLUSIONS Using ERPs recordings, the present study indicates the prolongation of P300 latencies in patients with severe GH deficiency and reduction of P300 amplitudes in patients with acromegaly. This study provides the electrophysiological evidence for the presence of cognitive dysfunction in both GH deficiency and GH excess, and different components of the cognitive performance are impaired in these conditions.

Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

Background: Manipulating thyroid hormones has been shown to influence learning and memory. Although a large body of literature is available on the effects of thyroid hormone deficiency on learning and memory functions during developmental or adult-onset hypothyroidism, electrophysiological findings are limited. This limitation is especially notable with respect to thyroxine administration in adult, normothyroid animals. Methods: Experiments were carried out on 12 adult male Wistar rats, each 9–10 months of age. Rats were randomly divided into hyperthyroid (0.2 mg/kg/day intraperitoneal thyroxine injection, for 21 days) and control groups (n = 6 animals in each group). Following spatial learning performance tests on hyperthyroid and control groups, rats were anesthetized with urethane and placed in a stereotaxic frame. A bipolar, tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted within the granule cell layer of the ipsilateral dentate gyrus to record field excitatory postsynaptic potentials (fEPSP). Following a 15-min baseline recording of fEPSPs, long-term potentiation (LTP) was induced by four sets of tetanic pulse trains. Results: Thyroxine-treated rats showed significantly worse performance in the spatial memory task and attenuated input-output relationships in the electrophysiological analyses. Treated rats also showed a lower efficacy of LTP induction when compared with controls. Conclusion: The present study provides clear in vivo evidence for the action of L-thyroxine in the impairment of synaptic plasticity and in inducing spatial memory task deficits in adult rats. These findings may explain the complaints of cognitive function reductions in hyperthyroid patients.

Experimental Hypothyroidism Delays Field Excitatory Post‐Synaptic Potentials and Disrupts Hippocampal Long‐term Potentiation in the Dentate Gyrus of Hippocampal Formation and Y‐Maze Performance in Adult Rats

Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6–7 months. Hypothyroidism was induced by administering 6‐n‐propyl‐2‐thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y‐maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post‐synaptic potentials. After a 15‐min baseline recording of field potentials, long‐term potentiation was induced by four sets of tetanic trains. The propylthiouracil‐treated rats showed a significantly attenuated input–output (I/O) relationship when population spike (PS) amplitudes and field excitatory post‐synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post‐tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats.

Maternal intake of Omega-3 essential fatty acids improves long term potentiation in the dentate gyrus and Morris water maze performance in rats.

Omega-3 fatty acid deprivation during development reduces performance in learning tasks, and dietary DHA supplementation improves learning ability and enhances long term memory in both young and old animals. However, little attention has been paid to the effect of maternal intake of Omega-3 fatty acids on hippocampal function in their pups. Randomly some of the pregnant dams were supplemented with Omega-3 essential fatty acid, others with tap-water, during pregnancy and breast-feeding by gavage daily. Spatial learning and memory was tested in Morris water maze. Field potentials from the dentate gyrus were recorded in response to medial perforant pathway in urethane-anesthetized pups. Omega-3-treated rats found the platform less traveled and closer to platform than control animals. However the pups from both groups show the same performance in retrieval task. No differences were found between corresponding animal groups in the input-output curves of the field potential slopes, suggesting no effect of Omega-3 supplementation on basal synaptic efficacy. Potentiation of population spike amplitude was much higher in pups of Omega-3 treated dams than control. Up to now Omega 3 fatty acid has been shown to be beneficial on the synaptic plasticity only under some pathological conditions. For the first time, we showed improved dentate gyrus-LTP and enhanced Morris water maze performance in healthy pups from healthy dams treated with Omega-3 fatty acids during pregnancy and breast-feeding period. Molecular studies are needed to explain Omega-3 effect on hippocampal synaptic plasticity.

Habituation of the Auditory Evoked Potential in a Short Interstimulus Interval Paradigm

The present experiment was carried out to investigate elicitation and habituation of the auditory event related potentials with stimulus trains utilizing a short interstimulus intervals (ISI) of 1500ms. Scalp event related potentials elicited by auditory stimuli were recorded in 10 male subjects. Thirty auditory stimuli were presented binaurally over headphones to every subject with a duration of 1000ms, each with a constant ISI of 1500ms. No task relevance was given to the stimuli. Wave-forms were collected using a Pentium 100 computer.

Electrodermal Activity in Nonmedicated Hyperthyroid Patients Having No Depressive Symptoms

The aim of the present study was to investigate whether the alteration in hypothalamic-pituitary-thyroid axis function results in electrodermal abnormality without causing marked psychiatric manifestations or not. Electrodermal activity was recorded with the skin conductance unit and IBM-AT computer. Basal levels of electrodermal activity (EDA), as well as responsivity to repeated insignificant acoustic stimulation were studied in 24 nonmedicated hyperthyroid patients and 35 healthy controls. The outcome of psychiatric rating scores indicated that patients had low anxiety scores and normal depression scores. The basal levels of thyroid hormones were higher in patients, when compared with the control group. On the analysis of EDA, we found lower onset latency and duration of the skin conductance response and higher skin conductance level in nonmedicated patients than healthy controls. The results above provide supporting evidence that the change of hypothalamic-pituitary-thyroid axis function results in abnormal EDA, without causing marked psychiatric manifestations.

The effect of immobilization stress on sensory gating in mice

Central sensory filtering processes can be demonstrated using a paired stimulus paradigm. Normal humans show a diminished, vertex-recorded midlatency (50 ms) of auditory evoked potential to the second of paired clicks (0.5 s apart), a phenomenon termed as auditory gating. A loss of 50 ms in auditory gating is strongly related to psychosis. The N40 auditory evoked potential (EP) in rats has been used to develop an animal model for the study of sensory gating mechanisms. Previous animal studies of auditory gating have used psychotomimetic drug administration to induce sensory gating. However, a nonpharmacologic model of deficient gating would be advantageous.In the present study we investigated the effect of immobilization stress on sensory gating in twelve adult male mice. Evoked responses to the paired auditory click stimuli from vertex location of scalp were recorded using a silver needle electrode, a bioelectric amplifier, and an analog-digital converter. The mice were exposed to immobilization stress (IS) for 3 h. Data showed that the N40 potential was depressed in response to the second of the paired stimuli before application immobilization stress. At the end of the 3-h immobilization, the depression of the second N40 response was not observed. It was concluded that sensory gating is present in the mice and acutely disrupted by stressful stimuli, as shown in human subjects and rats