Intraperitoneal Administration of Low Dose Aluminium in The Rat: How Good is It to Produce a Model for Alzheimer Disease.

Since neurotoxicity of aluminium (Al) resembles the progressive neurodegeneration observed in Alzheimer Disease (AD), Al administration in several ways has been used to produce AD model. Intraperitoneal (ip) low dose (4.2 mg/ kg) Al injection in rats for long periods is the preferred method by some researchers. In this paper, the efficiency of this method for producing an AD model was evaluated. In this study, we looked at the neuropathology of Al and the characteristic lesions of AD by histological and immunohistochemical techniques and determined oxidative stress markers in the brains of Al-treated and control rats. We also made electrophysiological recordings at the hippocampus and evaluated possible behavioural changes by Morris water maze test. However, no pathologic changes occurred in the animals except for an impairment in long-term potentiation (LTP) in the hippocampus (e.g. the LTPs of population spike (PS) amplitude at 15 min post-tetanus were measured as 217±27% in Al-treated rats and as 240±42% in sham-treated rats, of baseline PS amplitude). According to the findings of the present study, low dose of ip Al in rats is not sufficient to produce a good AD model. Higher doses (≥10 mg/kg) should be used.

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.

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.

Utility of P300 auditory event related potential latency in detecting cognitive dysfunction in growth hormone (GH) deficient patients with Sheehan's syndrome and effects of GH replacement therapy.

OBJECTIVE: Impaired cognitive function has been demonstrated in adults with growth hormone (GH) deficiency (GHD) by using different neuropsychological tests. Despite several studies, present knowledge about the impact of GHD and GH replacement therapy (GHRT) on cognitive function is limited. P300 event-related potential (ERP) application is a well-established neurophysiological approach in the assessment of cognitive functions including the updating of working memory content and the speed of stimulus evaluation. GHD is a well-known feature of Sheehan's syndrome and cognitive changes due to GHD and the effects of GHRT remain to be clarified. The present study was designed to investigate the effects of GHD and 6 months of GHRT on cognitive function in patients with Sheehan's syndrome by using P300 latency. DESIGN AND METHODS: The study comprised 14 patients with Sheehan's syndrome (mean age, 49.5+/-7.8 years) and 10 age-, education- and sex-matched healthy controls. With hormone replacement therapy, basal hormone levels other than GH were stable before enrollment and throughout the GHRT. The diagnosis of GH deficiency was established by insulin-tolerance test (ITT), and mean peak level of GH in response to insulin hypoglycemia was 0.77+/-0.35 mIU/l. Treatment with GH was started at a dose of 0.45 IU (0.15 mg)/day in month 1, was increased to 0.9 IU (0.30 mg)/day in month 2 and was maintained at 2 IU (0.66 mg)/day. Initially baseline auditory ERPs in patients and controls were recorded at frontal (Fz), central (Cz), and parietal (P3 and P4) electrode sites. In the patient group, ERPs were re-evaluated after 6 months of GH replacement therapy. During each session P300 amplitude and latency were measured. RESULTS: Mean serum insulin-like growth factor-I (IGF-I) concentration in the patient group before GHRT was 23+/-13 ng/ml. After 6 months of GH therapy mean IGF-I significantly increased to an acceptable level, 234+/-71 ng/ml (P<0.05). The mean latencies (at all electrode sites) of the patients before GHRT were found to be significantly prolonged when compared with those of normal controls (P<0.05). After 6 months of GHRT mean P300 latencies (at all electrode sites) were decreased significantly when compared with latencies before treatment (P<0.05). CONCLUSIONS: The present study, using P300 ERP latencies, therefore suggests an impairment of cognitive abilities due to severe GHD in patients with Sheehan's syndrome and an improvement of cognitive function after 6 months of physiological GHRT. Moreover, this was a novel application of P300 ERP latencies in cognitive function detection in patients with GHD. Further studies with different patient groups need to be done to assess the clinical use of this electrophysiological method in the diagnosis of cognitive dysfunction due to GHD.

The impact of acute dynamic exercise on intraocular pressure: role of the beta 2-adrenergic receptor polymorphism.

Effects of mutations in the beta 2-adrenergic receptor (beta 2AR) gene on intraocular pressure (IOP), in response to acute dynamic exercise, were investigated in 19 healthy males (age 22.6 +/- 2.8 years). Intraocular pressures were measured pre- and post-exercise. Weight, height, body mass index, and maximal oxygen (VO2max) uptake were recorded and subjects were genotyped for Arg16Gly, Gln27Glu and Thr164Ile mutations of the beta 2AR gene. Post-exercise, reductions in mean IOP values were found in 16 subjects with the Gly16Gly and Arg16Gly genotypes, but these values remained low in the eight patients with the Gly16Gly genotype 3 h post-exercise, whereas they returned to baseline within 1 h in the eight subjects with the Arg16Gly genotype. beta 2AR stimulation during exercise could be an important regulator of IOP response and determining beta 2AR polymorphisms may improve understanding of pathogenesis and treatment selection in ophthalmic diseases, e.g. glaucoma.

A comparison of the different interpair intervals in the conditioning-testing P50 paradigms.

The conditioning-testing P50 paradigm is used to demonstrate sensory gating of responsiveness to auditory stimuli. Sensory gating is measured in terms of a suppression of the second (test) P50 component in that paradigm. The time course of sensory gating can be determined by examining subjects' gating of responsiveness to stimuli repeated at various interpair intervals. In the present study auditory evoked potentials were recorded using a paired click, conditioning-testing P50 paradigm in 11 normal subjects with no family history of any psychotic disorder. Recordings were made at conditioning-testing intervals of 250 ms, 500 ms, 750 ms and 1000 ms. Whereas the grand averages of the P50 conditioning-testing response for the 250- and 500-ms intervals were 3.07% and 37.2%, respectively, indicating almost complete suppression, the grand averages of the ratios for the 750- and 1000-ms intervals were 114.35% and 92.92%, respectively, indicating little or no suppression. There was significant correlation in the C-T ratios with the increasing intervals. Our results suggest that the mechanism(s) responsible for sensory gating is activated mostly during the 500 ms after stimulus presentation. Other gating mechanism(s) functioning at longer intervals appear to be uncertain.

The relation between event related potential and working memory in healthy subjects.

In numerous investigations the P300-component of the event related potential has proved a valid indicator of memory activities. The present study explores the amplitude and latency of the components of event-related potential regarding short-term memory task. Event related potentials, elicited by auditory stimuli, were recorded in 40 healthy subjects. For evaluating short term memory capacity of a subject, software in Delphi for Windows language was written. Algorithm of the software was the presentation of randomly selected four different digits for 4 seconds, removing it and waiting for subject's response, adding one digit, if response was true, otherwise decreased by one. After 20 trials, mean of recall time for true answers was computed. The subjects with high recall time showed prolonged latency of P300. A positive correlation was found between P300 latency and recall time. No correlation was found between N1, P2 and N2 latency or amplitude and recall time. These results suggest that memory problems are well correlated with the abnormalities of P300.

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 1500 ms. 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 1000 ms, each with a constant ISI of 1500 ms. No task relevance was given to the stimuli. Wave-forms were collected using a Pentium 100 computer. All analyses were carried out over the 30 trials. In each single trial event related potentials, latencies and amplitudes of N1-P2 components were analyzed separately for four frequency bands (0.3-70, 0.3-4, 4-7, 7-13 Hz). Trend effects were tested with linear-regression analyses (N1-P2 amplitude x stimuli number). We found that the amplitude from the first stimulus decreased reliably across trial blocks of the N1-P2 components and that it was directly affected by ISI. The relevance of these results for the habituation is discussed.

Electrodermal activity in hypothyroid patients and healthy subjects.

The involvement of the central nervous system either in hypothyroidism or in hyperthyroidim has previously been shown on the basis of visual, auditory, somatosensory, and central motor evoked potential studies by some investigators. In to our previous study, we found that abnormal electrodermal activity in nonmedicated hyperthyroid patients was not associated with psychiatric symptoms. In this study, our purpose was to investigate whether hypothyroidism results in electrodermal abnormalities in the absence of measurable psychiatric symptoms. Electrodermal activity was recorded with a skin conductance unit connected to a personal computer. Basal levels of electrodermal activity and responsiveness to repeated acoustic stimulation were studied in 14 nonmedicated hypothyroid patients and 14 healthy controls. Psychiatric rating scores indicated that patients and healthy controls had normal levels of anxiety and depression. Hypothyroid patients had lower skin conductance levels, lower fluctation rates and prolonged onset latencies compared with controls. None of the hypothyroid patients had amplitude changes. In conclusion, hypothyroid patients may have abnormal electrodermal activity that is related to the change of hypothalamic-pituitary-thyroid axis function, without associated psychiatric symptoms.

The effect of sex differences on event-related potentials in young adults.

Female/male cognitive differences have been studied for some time; however, such differences in Turkish population is unknown. Evoked potentials (EPs) of the brain have been applied as an index of information processing in a wide variety of normal and cognitive impaired subjects. Scalp event-related potentials (ERP) evoked by auditory stimuli were recorded in 20 male and 18 female neurologically and audiologically normal young Turkish subjects of 18-25 years (Av. 20.6) of age. Standard auditory "Oddball" paradigm involving simple discrimination task of concentrating on infrequent (target) stimulus and ignoring frequent (non-target) stimulus was employed. EEG activity was recorded at the Fz, Cz, Pz and Oz electrode sites of the 10-20 system using Ag/AgCl electrodes. Wave forms were collected and averaged off-line by a Pentium 100 computer, which also controlled the stimulus presentation. In general, significant main effects of gender and electrode site on evoked potential components were found. The interpeak amplitudes N1-P2 and N2-P3 were higher in the male subjects than in the female subjects at Cz. N2-P3 were higher in the male subjects than in the female subjects at Oz. The latencies of N1, P2, N2, P3 components were not different between both sex. For both sexes we found that N1-P2 amplitude was higher at Fz and Cz than Pz and Oz. N2-P3 amplitude was higher at Fz than Oz for only female subject. In male subjects, latency of N2 was longer at Fz than Oz. There were no significant differences in the latencies of N1, P2, and P3 components between electrode sites in both sexes. We suggest that ERP components could be affected by sex, electrode site, and cognitive performance.

The effect of direction on saccadic eye movement parameters.

The present study obtained saccadic eye movements from 25 right-handed normal subjects (aged 18-35 yr, mean 22.4 yr) to examine the effects of saccade direction on saccadic parameters (latency, duration and average velocity). Binocular saccadic eye movements were recorded with a direct-current electrooculographic system, and analysis was performed on a laboratory digital computer. The LED target positions were randomly selected 10, 15, 20, 25 and 30 degrees to the left or right of the fixation points. In general, the mean values of the saccadic parameters over large saccade angles were in agreement with those previously reported. There were no significant differences between saccades directed to the right and to the left.

ELECTRODERMAL RESPONDING IN HYPERTHYROID PATIENTS.

The effects of hyperthyroidism on electrodermal habituation and responsiveness were examined in 43 hyperthyroid patients who were divided in two groups (medicated and unmedicated). In a comparison of 43 hyperthyroid and 43 normal controls; among patients with hyperthyroidism a great number of nonresponders were found. The distributions of SCR in habituation series in both group were almost the same but hyperthyroid patients were in slower habituation status than controls. These findings suggest that electrodermal nonresponsiveness or slow habituation in hyperthyroid patients might be considered as a function due to changes in the metabolism of biogenic mines in the central nervous system.

The relation between skin conductance level and plus-maze behavior in male mice.

The present study examined the correlation between anxiety scores and skin conductance level in 29 male Swiss Albino mice. Skin conductance (SC) was recorded with the SC unit and IBM-AT computer. Anxiety scores of mice were obtained from the elevated plus-maze test. The main result of the present study indicates that SC levels (SCLs) are negatively correlated with plus-maze behavior scores (both entries and time spent on the open arms). Our results are consistent with the findings which suggests that the higher the anxiety level the higher the SCL. This study further demonstrates the utility of SCL as a measurement for identifying anxiety in mouse. The interrelation between SCLs and plus-maze scores and possible explanations of the results are discussed.

Effect of reversed light-dark cycle on skin conductance in male rats.

Reversal of light-dark cycle was used to investigate the effect of the circadian changes on skin conductance, a tonic electrodermal activity parameter, in rats. Rats were adapted for 3 wk. to one of two lighting programs. The animals on the normal cycle were illuminated from 08.00-20.00; on the reverse cycle, from 20.00-08.00. Although during Week 1 to Week 3, skin conductance increased gradually in both groups, this increase was more dramatic in rats adapted to light from 20.00 to 08.00 than in the other group. When the animals on the reverse cycle were readjusted to a normal circadian cycle for 3 weeks, skin conductance decreased gradually to initial values. At Weeks 1, 2, 3, and 6, skin conductance was significantly higher in rats on the reverse light-dark cycle than in those on the normal cycle. The present data suggest that changes in normal light-dark conditions affect skin conductance in rats.

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.

Zinc-induced alterations in contractile properties of rat diaphragm muscle in vitro.

The effect of zinc ions on the isometric contraction of rat diaphragm muscles in the presence and in the absence of external calcium was studied. Using a transducer, the isometric force was measured as a function of supramaximal electrical stimulation, either directly or indirectly applied to the muscle. The following parameters were measured: peak twitch tension, PT, twitch contraction time, CT, relaxation half-time, RT-1/2, and peak rates of tension increase and decrease, +dP/dt and -dP/dt. The following zinc-induced alterations were observed: an increase of the PT; a decrease of the RT-1/2; an increase in the +dP/dt and -dP/dt. The CT was not changed significantly. Our results suggest that zinc ions have a positive inotropic effect on isolated diaphragm muscle. The increase in PT may be explained by a zinc-activated Ca2+ uptake by sarcoplasmic reticulum. This was followed by an increase in the rate of rise of tension development, which was secondary to increased -dP/dt. The mechanism(s) by which extracellular Ca2+ contributes to this action of zinc is not known.

Effect of zinc deficiency on chromosomal abnormalities in mice.

In the present study we investigated the effect of zinc-deficiency on chromosomal abnormalities and mitotic index, and the interaction of zinc-deficiency and methotrexate. Therefore, two zinc-deficient and two zinc-adequate diet received mouse groups were constituted. Methotrexate was injected to one of zinc-deficient and one of zinc-adequate diet groups. There were no structural and numerical abnormalities in all groups. However, mitotic index was significantly lower than other groups in zinc-deficient and methotrexate administered mice.

Has nicotine a local anaesthetic action?

In this study, we investigated whether nicotine may have a local anaesthetic action in mice, using the tail press and tail immersion tests. Nicotine increased the latent time of biting the clip in the tail press test (p < 0.001) and retarded tail withdrawal latency in the tail immersion test (p < 0.01), compared to controls. These results suggest that nicotine may possess a local anaesthetic action.

Effect of acute starvation on rat diaphragm function.

The effects of 130 h of acute starvation on diaphragm contractility fatigue were studied in isolated rat diaphragm strip preparations with phrenic nerve stimulation. Compared with controls, starvation produced a reduction in body and diaphragm weights. Twitch and tetanic tensions were reduced by starvation; however, when the force was calculated as the strength (normalized for the weight or muscle cross-section area of the diaphragm), no difference was observed between the control and experimental groups. Starvation induced a significant downward shift in the force-frequency relationship, and also increased diaphragm fatigability, but it had no effect on twitch contraction and relaxation time. We conclude that 130 h of acute starvation decreases diaphragmatic force and endurance, but the strength does not change, because of the reducing diaphragmatic mass.

Effect of nicotine on swimming exercise in rats.

In this study, endurance time in swimming exercise was evaluated in rats. Subcutaneous (S.C.) injection of nicotine decreased the endurance time in swimming exercise significantly, in a dose-dependent manner compared to the control group. At the dose of 0.125 mg/kg nicotine, the endurance time in swimming exercise remained unchanged, while at the doses of 0.25 and 0.375 mg/kg, it decreased significantly (p < 0.05 and p < 0.01, respectively). This effect of nicotine was antagonized by pretreatment with hexamethonium 5 mg/kg S.C. These results suggest that nicotine may limit the physical performance.