Seizure frequency and bioelectric brain activity in epileptic patients in stable and unstable atmospheric pressure and temperature in different seasons of the year--a preliminary report

Background and purposeAn epileptic seizure is a sum of exogenous and endogenous factors affecting an epileptic focus. The aim of the study was to examine the influence of changes in atmospheric pressure and temperature on the increase in the frequency of seizures and changes in EEG in epileptic patients.Material and methodsThe study included 30 epileptic patients (aged 19–54) reporting the influence of changes in weather conditions on the increase in the frequency of seizures for at least 2 years. EEG was performed twice each season at the time of stable and unstable weather conditions.ResultsIn stable and unstable weather conditions, epileptic changes in EEG were most often found in winter (in 43.3% and 63.3% of patients, respectively). Unstable weather conditions increased the proportion of patients with epileptic changes in EEG also in the other seasons. Unstable weather conditions caused an increase in the frequency of seizures in 40% of patients in spring, 43.3% in autumn, 40% in winter and in approximately 7% in summer.ConclusionsIn spring, autumn and winter, unstable weather conditions cause an increase in the frequency of seizures in almost half of the epileptic patients but only in 7% in summer. The increase in frequency of seizures in unstable weather conditions did not correspond in all patients with increase of changes in EEG. The higher proportion of epileptic patients with changes in EEG in unstable weather conditions in all seasons suggests an impact of these conditions on subclinical seizure discharges in this period.     

Localization and pharmacological modulation of GABA-B receptors in the globus pallidus of parkinsonian monkeys

Changes in GABAergic transmission in the external and internal segments of the globus pallidus (GPe and GPi) contribute to the pathophysiology of the basal ganglia network in Parkinson's disease. Because GABA-B receptors are involved in the modulation of GABAergic transmission in GPe and GPi, it is possible that changes in the functions or localization of these receptors contribute to the changes in GABAergic transmission. To further examine this question, we investigated the anatomical localization of GABA-B receptors and the electrophysiologic effects of microinjections of GABA-B receptor ligands in GPe and GPi of MPTP-treated (parkinsonian) monkeys. We found that the pattern of cellular and ultrastructural localization of the GABA-BR1 subunit of the GABA-B receptor in GPe and GPi was not significantly altered in parkinsonian monkeys. However, the magnitude of reduction in firing rate of GPe and GPi neurons produced by microinjections of the GABA-B receptor agonist baclofen was larger in MPTP-treated animals than in normal monkeys. Injections of the GABA-B receptor antagonist CGP55845A were more effective in reducing the firing rate of GPi neurons in parkinsonian monkeys than in normal animals. In addition, the injections of baclofen in GPe and GPi, or of CGP55845A in GPi lead to a significant increase in the proportion of spikes in rebound bursts in parkinsonian animals, but not in normal monkeys. Thus, despite the lack of changes in the localization of GABA-BR1 subunits in the pallidum, GABA-B receptor-mediated effects are altered in the GPe and GPi of parkinsonian monkeys. These changes in GABA-B receptor function may contribute to bursting activities in the parkinsonian state.     

The spontaneous firing pattern of forebrain neurons. I. The effects of dopamine and non-dopamine depleting lesions on caudate unit firing patterns

Unilateral lesions in and around the course of the nigrostriatal pathway (in the substantia nigra, in the supranigral region and more rostrally in the area of the medial forebrain bundle) in cats produced a marked slowing of single unit firing in the caudate nucleus contralateral to the lesion. In addition, the medial forebrain bundle lesion produced a tendency for an increase in unit firing rates in the caudate nucleus ipsilateral to the lesion. Lesions in the supranigral region in monkeys produced indications of a slowing in the firing rate of single units in the contralateral caudate and an increase in the firing rate of units in the caudate ipsilateral to the lesion. These alterations in spontaneous unit firing were independent of lesion-induced changes in concentrations of striatal dopamine or the activities of tyrosine hydroxylase and DOPA decarboxylase.     

Tissue levels of leu-enkephalin in rats with adjuvant arthritis

To study the level of leu-enkephalin in bone and joint tissues and in the spinal cord of rats with adjuvant arthritis, arthritis was induced in Lewis rats by the injection of Mycobacterium butyricum in Freund's incomplete adjuvant (FIA). Immunoelectron microscopy (IEM) was used to monitor the cellular distribution of leu-enkephalin in control and arthritis groups, and radioimmunoassay (RIA) was used to measure the concentration in the tissues. The results of IEM showed increased levels of leu-enkephalin in the matrix of the sciatic nerve, in nerve fibres in the synovial membrane and periosteum, as well as in fibroblasts and endothelial cells of the periosteum in arthritic groups. In macrophage-like cells of the synovial membrane as well as monocyte and polymorphonuclear lineage cells in the bone marrow, the level of leu-enkephalin was decreased in the arthritic group. The results of RIA showed that the concentration of leu-enkephalin was lower in the ankle and increased in the spinal cord of arthritic animals compared with controls. In conclusion, leu-enkephalin levels were decreased in joints and in bone marrow, but increased in nerve tissues in the group with arthritis. Further studies are needed to show whether leu-enkephalin is involved in a process that serves to limit the effect of immunisation.     

Neuronal hemoglobin is reduced in Alzheimer's disease, argyrophilic grain disease, Parkinson's disease, and dementia with Lewy bodies

Previous studies have demonstrated the presence of hemoglobin α-chain and β-chain in neurons of the rodent and human brain thus indicating that hemoglobin is a normal component of nerve cells and that hemoglobin may play a role in intraneuronal oxygen homeostasis. Progressing with these studies, hemoglobin expression has been examined in selected cell population in the brains of Alzheimer's disease (AD), argyrophilic grain disease (AGD), Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). Double labeling immunofluorescence and confocal microscopy revealed reduced hemoglobin α-chain and β-chain in practically all neurons with small amounts of granular or punctuate hyperphosphorylated tau deposits and in neurons with tangles in the hippocampus and frontal cortex in AD and in the hippocampus in AGD; in ballooned neurons containing αB-crystallin in the amygdala in AD and AGD; and in about 80% of neurons with punctuate α-synuclein deposits and in neurons with Lewy bodies in the substantia nigra pars compacta and in vulnerable neurons of the medulla oblongata in PD and DLB; and in neurons with Lewy bodies in the frontal cortex in DLB. Hemoglobin immunoreactivity was also observed in the core of neuritic plaques and in diffuse plaques, but not in dystrophic neurites. Loss of hemoglobin was specific as neuroglobin was present equally in neurons with and without abnormal protein inclusions, and erythropoietin receptor was expressed equally in neurons without and in neurons with abnormal protein aggregates in AD, AGD, PD, and DLB.     

Bilirubin encephalopathy: a study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases

Bilirubin encephalopathy (BE), which includes acute (kernicterus) and chronic (postkernicteric) forms, results from severe neonatal jaundice. In order to investigate neurodegenerative mechanisms in autopsy cases of BE, we immunohistochemically examined expressions of neurotransmitters, neuropeptides, and calcium-binding proteins in the basal ganglia; and deposition of oxidative products. Expression of tyrosine hydroxylase was reduced in the putamen in cases of acute BE, and in the globus pallidus in cases of acute and chronic postkernicteric BE. Methionine-enkephalin expression was reduced in the external segment of the globus pallidus in cases of acute and chronic postkernicteric BE, and immunoreactivity for substance P was severely altered in both internal and external segments in cases of chronic postkernicteric BE. A decrease in the number of parvalbumin-immunoreactive interneurons in the external segment of the globus pallidus was observed predominantly in cases of acute BE, whereas the number of interneurons immunoreactive for calbindin-D28K was reduced in the putamen in cases of chronic postkernicteric BE. Nuclear immunoreactivity for 8-hydroxy-2'-deoxyguanosine was seen in the putamen in half of the BE cases. These findings indicated that the putamen was impaired in BE and the pallidal external segment was also damaged in the acute form of BE, suggesting that oxidative damage to DNA is implicated in lesions of the basal ganglia.     

Classification of neurons in the ectosylvian auditory cortex of the dog

The rapid Golgi method was used to classify the neurons in the MES and PES auditory areas of the dog. Small pyramids were found in layer II with percentages of 12% in the MES area and 8.1% in the PES area. Medium sized pyramids possessed a bimodal distribution, the first in layer IV and the second in V, with 58% in MES and 62% in PES. Large pyramids were found in layer V with a proportion of 12.5% in MES and 17% in PES. The star neurons were found in layer III with proportions of 5.9% in MES and 4.0% in PES. The double bouquet neurons in layer III had a proportion of 1.5% in MES and 1.7% in PES. Fusiform neurons in layers V and VI were in proportions of 2.2% in MES and 6.4% in PES. The principal finding was a special auditory cell occurring in layers V and VI of the MES area with a proportion of 8% and from 14.8 to 34.8% in the strata between 1 and 2 mm. Less than 1% of neurons in the PES area were identified as special cells. Its appearance was an inverted pyramidal cell with a large dendrite extending toward the white matter from which the axon arose.     

Altered Cholinergic Mechanisms and Blood Pressure Regulation in the Rostral Ventrolateral Medulla of DOCA-Salt Hypertensive Rats

We examined whether cholinergic transmission in the rostral ventrolateral medulla (RVLM) of deoxycorticosterone acetate-salt hypertensive rats (DHR) is enhanced and the enhancement is involved in the maintenance of hypertension in DHR, and whether cholineacetyltransferase (ChAT) activities and ChAT mRNA expression are enhanced in neurons intrinsic to the RVLM of DHR. Rats were anesthetized, paralyzed, and artificially ventilated. Unilateral microinjection of cholinergic agents into the RVLM produced a pressor response. The pressor response to physostigmine was greater in DHR than in control rats, whereas the response to carbachol was the same in both sets of rats. Bilateral microinjection of scopolamine into the RVLM produced a decrease in blood pressure. The depressor response was greater in DHR than in control rats. The number of ChAT-activity-detected neurons in the RVLM was greater in DHR than in control rats. The number of ChAT mRNA-expressing neurons in the RVLM was also clearly greater in DHR than in control rats. These results demonstrate that cholinergic transmission in the RVLM is enhanced in DHR, and this enhancement may play a role in the maintenance of hypertension in DHR. It is probable that enhanced activity of cholinergic neurons intrinsic to the RVLM is at least in part, responsible for the enhanced cholinergic transmission in the RVLM of DHR.     

Age-related alterations in immunoreactivity of the midsized neurofilament subunit in the brainstem reticular formation of the cat

In the present study, we compared the immunoreactivity of the midsized subunit of neurofilaments (NF-M) in the brainstem reticular formation of adult and old cats. There was a dramatic decrease in immunoreactivity in most reticular nuclei in the old cats. The most obvious reduction in these regions occurred in dendritic arborizations. In contrast, a small number of nuclei showed a slight increase in immunoreactivity in the aged animals. The age-related changes in immunoreactivity indicate that there is an alteration of NF-M content in reticular neurons and their processes in old age. Such changes in NF-M content may be the basis for the alterations in the morphology of reticular neurons in aged animals.     

Posterior hypothalamus cholinergic stimulation-induced activation of anterior hypothalamic area neurons is enhanced in spontaneously hypertensive rats

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA neurons are enhanced in spontaneously hypertensive rats (SHR). In addition, we have demonstrated that cholinergic mechanisms in the posterior hypothalamic nucleus (PHN) are involved in the activation of AHA angiotensin-II-sensitive neurons. It has been suggested that cholinergic function in the posterior hypothalamus is enhanced in SHR and that this hyperactivity plays a role in hypertension in SHR. In the present study, we examined whether the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is altered in SHR. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY) were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of the cholinoceptor agonist carbachol, the cholinesterase inhibitor physostigmine and the excitatory amino acid glutamate into the PHN caused increases in firing rate of AHA angiotensin-II-sensitive neurons in anesthetized WKY and SHR. The increase in firing rate of AHA neurons induced by these drugs was enhanced in SHR as compared to WKY. The enhancement of the physostigmine-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. The enhancement of the glutamate-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. Microinjection of scopolamine, a cholinoceptor antagonist, into the PHN caused a small but significant decrease of firing rate of AHA angiotensin-II-sensitive neurons in SHR but not in WKY. These findings indicate that the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is enhanced in SHR and that PHN cholinergic mechanisms are involved in tonic activation of angiotensin-II-sensitive neurons in the AHA of SHR. It appears that the enhancement of the PHN cholinergic stimulation-induced activation of AHA neurons in SHR results mainly from the enhanced neural reactivity to angiotensins in AHA neurons of SHR.     

A Comparison of β-Amyloid Deposition in the Medial Temporal Lobe in Sporadic Alzheimer's Disease,Down's Syndrome and Normal Elderly Brains

The density of β-amyloid (Aβ) deposits was studied in the medial temporal lobe in non-demented individuals and in sporadic Alzheimer's disease (SAD) and Down's syndrome (DS). No Aβdeposits were recorded in six of the non-demented cases, while in a further eight cases, these were confined to either the lateral occipitotemporal or parahippocampal gyrus. The mean density of Aβ deposits in the cortex was greater in SAD and DS than in non-demented cases but with overlap between patient groups. The mean density of Aβ deposits was greater in DS than SAD consistent with a gene dosage effect. The ratio of primitive to diffuse Aβ deposits was greater in DS and in non-demented cases than in SAD and the ratio of classic to diffuse deposits was lowest in DS. In all groups, Aβ deposits occurred in clusters which were often regularly distributed. In the cortex, the dimension of the Aβ clusters was greater in SAD than in the non-demented cases and DS. The data suggest that the development of Aβ pathology in the hippocampus could be a factor in the development of DS and SAD. Furthermore, the high density of Aβ deposits, and in particular the high proportion of primitive type deposits, may be important in DS while the development of large clusters of Aβ deposits may be a factor in SAD.     

Prevalence of mental disorders in a 70-year-old urban population

The prevalence of mental diseases and abnormalities in a representative, systematic sample of 70-year-olds in Gothenburg, Sweden, is presented. Out of 460 selected subjects, 392 (85.2 %) took part and the responders and non-responders were similar in several respects. A case was defined by cut-off points on symptom and/or sign rating scales and diagnoses were defined operationally but as closely as possible to the ICD-classification. The total psychiatric morbidity, excluding personality deviations, was 16.9% in men and 26.1% in women, and excluding also mild neuroses 12.7% in men and 15.5% in women. The prevalence of psychoses was 3.0% in men and 3.5% in women, of neuroses of moderate-severe degree 6.6% in men and 11.5% in women, of neuroses of mild degree 4.2% in men and 10.6% in women, of alcoholism 3.0% in men and 0.0% in women and of oligophrenia 0.0% in men and 0.4% in women. The prevalence of demential syndromes of a psychotic degree was 2.4% in men and 1.3% in women, of a neurotic degree 4.2% in men and 1.8% in women and the total prevalence of demential syndromes was thus 6.6% in men and 3.1% in women. Indications of previous alcohol problems and no or a low current consumption of alcohol were noted among 18.1% of the men.     

水通道蛋白-4在颞叶癫痫儿童致痫灶组织中表达的初步研究

目的探讨水通道蛋白-4(AQP-4)在颞叶癫痫儿童致痫灶组织中的表达及其在癫痫发作中的意义。方法 2010年1月至2011年6月手术治疗颞叶癫痫儿童患者13例和同期脑深部肿瘤儿童患者7例,分别取切除的致痫灶脑组织和正常脑皮层组织行AQP-4表达的免疫组化染色检测,比较它们AQP-4表达水平的差异。结果正常组脑组织中灰质、白质均有AQP-4表达,主要表达在血管周围星形细胞足突膜上,表达分布存在一定规律性,即集中在细胞与血管接触面;6例表达强度为(++),1例表达强度为(+++)。致癫痫脑组织中AQP-4主要在发育不良神经元周围的胶质细胞中表达,分布无明显规律性;3例AQP-4表达强度为(++),10例表达强度为(+++)。两组AQP-4表达强度有明显差异(P<0.05)。结论 AQP-4在颞叶癫痫儿童致痫灶脑组织中表达强度明显高于正常大脑皮层。AQP-4可能介导了儿童颞叶癫痫的发生。     

Roles of neurotransmitter amino acids in seizure severity and experience in the genetically epilepsy-prone rat

This investigation was designed to compare seizure-naive and seizure-experienced genetically epilepsy-prone rats (GEPRs) in order to distinguish transmitter amino acid changes related to seizure severity from those associated with seizure experience. Moderate (GEPR-3) and severe (GEPR-9) seizure male GEPRs were divided into seizure-naive and seizure-experienced groups based on whether seizure-inducing acoustical stimuli had been presented between 45 and 60 days of age, and then were sacrificed at76 ± 3 days. γ-Aminobutyric acid (GABA) concentrations were lower in both GEPR-3s and GEPR-9s compared to non-epileptic controls in each brain region examined. Aspartate content was elevated in 5 of 6 brain areas in GEPR-9s compared to non-epileptic controls, and in 3 regions was higher in GEPR-9s than in GEPR-3s. In contrast, taurine concentrations were higher in GEPR-3s than in non-epileptic controls in each region, and in 4 areas were higher in GEPR-3s than in GEPR-9s. Changes resulting from seizure experience consisted of increases in aspartate, glutamate and glycine in seizure-experienced compared to seizure-naive groups in inferior colliculus and in motor-sensory and frontal cortices. These findings suggest that the high levels of taurine in GEPR-3s and the elevated content of aspartate in GEPR-9s have roles as determinants of seizure severity. The low concentrations of GABA in both types of GEPRs are consistent with a role for this amino acid in determination of seizure susceptibility. Furthermore, the seizure-induced changes in aspartate and glutamate in both types of GEPRs support the concept that these excitatory amino acids mediate changes in seizure predisposition. The current results are in agreement with previous studies indicating that imbalances in neurotransmitter amino acids are important factors in determinig seizure behavior in the GEPR.     

Asymmetric molecular forms of acetylcholinesterase in mammalian skeletal muscles

Velocity sedimentation analysis of acetylcholinesterase (AChE) molecular forms was performed separately in endplate-rich and endplate-free regions of the diaphargm muscle of the rat, guinea pig, rabbit, dog, and pig, and in mm. erectores trunci and m. vastus lateralis in man. Several high-ionic-strength media were first tested to achieve better solubilization of AChE from rat muscles than by the usual 1 M NaCl- Triton X-100 medium. Ninety-five percent of the rat diaphragm was solubilized in a single extraction step by medium containing 1 M lithium chloride instead of NaCl. Homologous molecular forms of AChE were found in all species. The asymmetric forms were invariably present in the endplate regions of muscles but their activity in endplate-free regions was much lower than in endplate regions in all investigated mammals except in man. Essentially the same pattern of AChE molecular forms was present in both regions in human muscles. High extrajunctional activity of the asymmetric forms makes human muscles similar to immature rodent muscles in vivo and in culture. The pattern of AChE molecular forms in the endplate region of the diaphragm in senile 24-month-old rats was not significantly different from that in 3-month-old animals. The persistence of the asymmetric AChE forms in the diaphragm of senile rats suggests that neuromuscular interactions do not become deficient with age in this muscle.     

Sexually dimorphic distribution of neurotensin/neuromedin N mRNA in the rat preoptic area

Neurotensin release from estrogen-responsive neurons in the rostral preoptic area of the female rat may play an important role in triggering preovulatory secretion of gonadotropin-releasing hormone on proestrus. We investigated the possibility of sexually differentiated biosynthesis of neurotensin in the rostral preoptic area, using in situ hybridization histochemistry to detect neurotensin/neuromedin N (NT/N) mRNA in adult male rats and adult female rats at proestrus and the first day of diestrus. In sections through the anteroventral periventricular nucleus (AVPv), the number of labeled cells in proestrous females was four times that in males. Diestrus females exhibited half the number of labeled cells present at proestrus, and there was evidence for a significant correlation between circulating estradiol level and number of labeled cells in the AVPv. In the rostral portion of the medial preoptic nucleus (MPN), two contiguous groups of labeled cells were especially prominent. One group, in the medial half of the MPN, was located closer to the midline in females than in males and displayed greater labeling in males than in females. Furthermore, labeling in the rostral MPN was greater at proestrus than at diestrus. These results indicate that biosynthesis of neurotensin and neuromedin N in the rostral preoptic area may be sexually differentiated and, in the female, may vary across the estrous cycle in parallel with circulating estradiol levels, consistent with the view that neurotensin neurons in this area are involved in the regulation of preovulatory secretion of gonadotropin-releasing hormone. The sex- and region-specific expression of NT/N mRNA in the rostral preoptic area suggests functional heterogeneity of neurotensin neuronal populations in this area and implies complex regulation of NT/N gene expression in the rat brain.     

Involvement of Cholecystokinin in Food Intake: II. Lactational Hyperphagia in the Rat

The role of Cholecystokinin in the hyperphagia of lactation was studied by measuring the concentration of this hormone in plasma and cerebrospinal fluid in relation to food intake in lactating rats. Cholecystokinin was measured by high-performance liquid chromatography and radioimmunoassay in plasma and by radioimmunoassay in cerebrospinal fluid. Plasma concentrations of Cholecystokinin were increased in freely-fed lactating rats compared with non-lactating, regularly cycling rats. However, after 24 h of food deprivation the concentration of plasma Cholecystokinin was markedly decreased in the lactating rats to levels which were lower than those of non-lactating animals. Furthermore, plasma levels of Cholecystokinin did not increase in response to 1 h of feeding in lactating rats, whereas in non-lactating rats they did. In contrast, the concentration of cholecystokinin-like immunoreactivity in the cerebrospinal fluid was the same in freely-fed lactating and non-lactating rats. As in plasma, food deprivation markedly decreased the levels of cholecystokinin-like immunoreactivity in the cerebrospinal fluid of lactating rats but unlike in plasma, the levels were restored by feeding. The levels of cholecystokinin-like immunoreactivity were not changed under these conditions in the non-lactating rats. These results show that there is no correlation between the concentration of Cholecystokinin in plasma and cerebrospinal fluid, which supports the suggestion that the cholecystokinin-like immunoreactivity in the cerebrospinal fluid is derived from the brain. Removal of the litter from lactating rats deprived of food for 24 h reduced food intake and increased the concentration of cholecystokinin-like immunoreactivity in the cerebrospinal fluid, but not in plasma. The inhibition of food intake caused by an intraperitoneal injection of Cholecystokinin octapeptide increased after litter removal. It is suggested that hunger in the lactating rat is reflected by a decrease in the levels of cholecystokinin-like immunoreactivity in the cerebrospinal fluid and satiety by the restoration of these levels.     

Changes in nerve cell bodies during the myelination of their axons

Changes in nerve cell perikarya were studied at twelve phases of the myelination period of rat sciatic nerve; data are given on nuclear and nucleolar diameters, the area of cytoplasm, neuronal packing density, length of the nerve, limb and femur, and on the distribution of chromophil substance in the cytoplasm. The study was coordinated with and supplements a previous quantitative electron microscopic study of myelination in rat sciatic nerve. The amounts of cytoplasm in anterior horn motor cells and in large cells of the spinal ganglia increased during myelination, and growth curves for these two cell populations were nearly identical. The increase in cytoplasm was compared with the increase in axoplasm, calculated from the increase in caliber and in fiber length. The volumes of axoplasm and of cytoplasm in the perikarya increased in strict proportion, indicating a coordinated growth of axons and perikarya during the myelination period. Axon growth in turn, occurs in strict coordination with myelin deposition. The growth curve for the small cells in spinal ganglia differed entirely and is consistent with the assumption that nonmyelinated or very thinly myelinated fibers arise from these cells. Changes in the volume of cytoplasm in nerve cells were associated with changes in the nucleo-cytoplasmic relation, a decrease in neuronal packing density, and a redistribution of RNA in the cells.     

Age-dependent loss of PTP and LTP in the hippocampus of PrP-null mice

We have investigated synaptic function in the hippocampus in mice of different ages carrying a null mutation in the PrP gene. Experiments carried out in vivo and in vitro in two laboratories revealed no differences in the ability of juvenile and young adult control and PrP-null mice to express long-term potentiation, paired-pulse facilitation, or posttetanic potentiation in either the dentate gyrus or in the CA1 region. However, we found a significant reduction in the level of posttetanic potentiation and long-term potentiation in the CA1 region of aged PrP-null mice. These results are discussed in relationship to reported increased levels of oxidative stress in older PrP-null mice.