Three experiments were performed to assess the interanimal transferability of conditioned taste aversion to 0.1% saccharin. Two experiments used an intracerebrospinal fluid (subdural) route for administering brain extracts and a third used an intraperitoneal (IP) route. As assessed by repeated measurements ANOVA, saccharin consumption was significantly lower during extinction of conditioned aversion for experimental recipients (ER) receiving extracts from aversively conditioned donors, than that of control recipients (CR), receiving extracts from unconditioned donors in one subdural experiment, F(21, 189) = 1.61, p less than 0.05. In the IP experiment the results were in the same direction, though not significant, F(34, 238) = 1.39, p less than 0.1. Results of the other subdural experiment are discussed. It is concluded that these experiments with the conditioned taste aversion paradigm have potential as a model for investigations of behavioral interanimal transfer (BIT) and for neuromolecular research aimed at identification of associated putative neurochemical(s) and the elaboration of their mechanism of action.
To test the hypothesis that a narrow intensity band of geomagnetic activity contributes to Sudden Infant Death, 32 pregnant rats were exposed for two to three days before expected parturition either to a coil that generated 0.5 Hz sine-wave, 5 to 10 nanoTesla magnetic fields, or to a reference coil (<1 nT) in the same room. The field was off for 30 min every 4 h during the exposure. The orientation of the coils was perpendicular in space and activated alternately in four blocks of experiments. The litters born to the exposed mothers contained significantly fewer pups (M = 14.1,SD= 2.1) than those exposed to the control conditions (M = 16.2, SD = 2.7). There were significantly fewer numbers of males and fewer numbers of females in litters exposed to the fields generated in the east-west and north-south directions, respectively. These results support the hypothesis that a specific temporal configuration of brief periods of geomagnetic activity can produce an increased incidence of nonvital fetuses, neonates, or infants.
The behavioral effects of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME), when perinatally (2 d prenatal-14 d postnatal) co-administered with extremely low frequency magnetic fields, were examined in weanling and adult rats. Litters of rat pups and their dams were exposed continuously to biphasic pulsed fields presented once every 2 s. The magnetic fields were amplitude modulated in successively increasing and decreasing steps (each 30 min) between 0 and 1.8 microT or between 0 to 13 nanoT (reference field) during 4-h periods (6 periods per day). These two treatments were subdivided into dams that received tap water and dams that received 1.0 g/L L-NAME in tap water. The behavioral sequelae to these treatments for 242 progeny from 41 litters were followed from weaning (1 wk after termination of treatment) into adulthood. Compared to exposures to water and nanoT magnetic fields, perinatal exposures to the microT magnetic fields or to L-NAME in the maternal water supply were associated with increased activity levels when the rats were tested as weanling, but decreased activity levels when the rats were tested as adults. However, the activity of rats that received the combination of L-NAME and microT magnetic fields did not differ significantly from the activity of the rats that had received water and the nanoT fields. Long-term (adulthood) effects of these perinatal treatments on associative learning, as inferred by learned fear to contextual stimuli, were not evident. These results indicate that L-NAME and this particular pattern of magnetic field antagonized one another when co-administered during the perinatal period.
Pregnant Wistar rats were exposed to either 0.5 Hz Rotating Magnetic Fields (50 microT to 300 microT or 1.5 mT to 3.0 mT) or to sham field or control environments for 3 days before to 3 days after the day of birth. The adult male offspring that had been exposed perinatally to the RMF displayed significantly heavier testicle weights but fewer neurons within the medial preoptic nucleus (MPO) and caudal ventromedial hypothalamus relative to sham field controls (effect size about 30%). There was no statistically significant difference between the two ranges of RMF intensities for these measures. RMF-exposed rats relative to sham-field exposed rats did not differ with respect to spleen weights, body weights, or mounting (reproductive) activity. The heavier testicle weights replicated previous studies and suggest that permanent, selective alterations in neuronal density can also occur subsequent to perinatal exposure to relatively weak, extremely low frequency magnetic fields.
Recent advances in functional magnetic resonance imaging (fMRI) at > or = 1.5 T magnetic field strength and with high speed single-shot echo planar imaging techniques have made it possible to monitor local changes in cerebral blood volume, cerebral blood flow, and blood oxygenation level in response to sensory stimulation, simple motor activity, and possibly also to more complex cognitive processing. However, fMRI has also been accomplished on conventional MR scanners of medium field strength (approximately 1.0 T) using special pulse sequences and appropriate methods for image analysis. We present results from six subjects on photic stimulation using a standard 1.0 T MR scanner together with special software for off-line image analysis. Continuous serial T2-weighted imaging were performed for 6 minutes in the plane of the calcarine fissure. There were 3 repetitions of 1 minute resting state of darkness (OFF) and 1 minute activated state (ON) with 8 Hz flicker stimulation. To directly map these functional images to the underlying anatomy we also acquired a high resolution T1-weighted image from the same axial slice. The results demonstrated that stimulus-related signals can be obtained from primary visual cortex with a conventional 1.0 T MR scanner. Further methodological improvements are discussed and related to present and future possibilities for the use of fMRI within psychophysiology.
The brains of three Alzheimer patients aged 93, 94, and 104 years old were analyzed. Although cell death was apparent in different cortices, the prefrontal cortex and the Broca's appeared to be hit hardest. The different CA areas of the hippocampal formation all displayed equivalent degrees of cell death but the entorhinal areas showed the most severe degree of cell degeneration. Both apoptosis and necrosis were observed in the different cerebral regions of these very old patients, as expected.
Abstract Several studies have been conducted in recent years to evaluate the risk of Parkinson's disease (PD) and polymorphisms of interleukin -10(IL-10). However, the results were conflicting. Therefore, we performed this meta-analysis of published case-control studies to assess this association. Systematic searches of electronic databases PubMed Web of Science, BIOSIS Previews, Science Direct, Chinese Biomedical Database, WANFANG Database,and Chinese National Knowledge Infrastructure with hand searching of the references of identified articles were conducted. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 7 case-control studies involving 1912 PD cases and 1740 controls were included, concerning two polymorphisms (-1082A/G and -592C/A) of IL-10 gene. No significant associations were found in the overall analysis for both -1082A/G and -592C/A polymorphisms with PD risk. Similar lacking associations were observed in subgroup analysis based on ethnicity and age of onset. In conclusion, there is no enough evidence for association between IL-10 polymorphisms (-1082A/G and -592C/A) and risk of PD at present. Well-designed studies with larger sample-size and multiethnicity studies are warranted in the future.
This study assessed the presence of internalizing psychological problems in 9- to 11-year-old males diagnosed with attention deficit hyperactivity disorder (ADHD). The participants' raw scores on the Behavior Assessment System for Children (BASC) Parent Scale, Teacher Rating Scale, and Self-Report of Personality (Reynolds & Kamphaus, 1992) along with the Revised Children's Manifest Anxiety Scale (Reynolds & Richmond, 1985) were compared to the normative sample for each respective measure. The results found that ADHD children presented with significantly (p <.05) higher levels of both anxiety and depression on the BASC and anxiety on the RCMAS when ratings were completed by parents, teachers, and self-report. The results were discussed in terms of the comorbidity of internalizing disorders with ADHD children and need to consider differential behavioral and medical intervention.
We extended the work of Rouleau et al. (I. Rouleau, D. P. Salmon, N. Butters, C. Kennedy, & K. McGuire, Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease. Brain and Cognition, 18, 1992, 70-87) and Ryan et al. (J. J. Ryan, S. J. Lopez, & S. W. Sumerall, Base rate of "10 to 11" clocks among patients referred for neuropsychological evaluation. Perceptual and Motor Skills, 81, 1995, 1138) by providing base rates for "10 to 11" clocks in samples of healthy elderly (n = 168), Alzheimer's disease (AD; n = 81), and Parkinson's disease (PD; n = 105). Groups were comparable in age and education. Stimulus bound clocks occurred in 3.0% of controls, 30.9% of AD, 5.7% of PD, and 10.2% of the combined sample. The 10.2% base rate is consistent with Ryan et al. for a mixed sample and Rouleau et al. for healthy elderly and patients with AD or Huntington's disease.
Cytidine-5'-diphosphocholine (citicoline or CDP-choline) is an essential endogenous intermediate in the biosynthesis of phosphatidylcholine. In the present study, primary dopaminergic cultures from mouse mesencephala were treated with citicoline to investigate its neuroprotective potential on the survival of dopaminergic neurons exposed to MPP(+) and glutamate. Treatment with citicoline alone significantly increased the survival of dopaminergic neurons compared to controls. MPP(+) or glutamate decreased the total number of dopaminergic neurons whereas citicoline afforded significant protection against either toxicity. Moreover, citicoline significantly decreased propidium iodide uptake by cultured cells. The study concludes that citicoline exerts stimulant and neuroprotective actions on cultured dopaminergic neurons.
Functional magnetic resonance imaging (fMRI) has helped to elucidate the neurobiological bases of psychiatric and neurodevelopmental disorders by localizing etiologically-relevant aberrations in brain function. Functional MRI also has shown great promise to help understand potential mechanisms of action of effective treatments for a range of psychiatric and neurodevelopmental disorders, including mood and anxiety disorders, schizophrenia, and autism. However, the use of fMRI to probe intervention effects in psychiatry is associated with unique methodological considerations, including the psychometric properties of repeated fMRI scans, how to assess potential relations between the effects of an intervention on symptoms and on specific brain activation patterns, and how to best make causal inferences about intervention effects on brain function. Additionally, the study of treatment effects in neurodevelopmental disorders presents additional unique challenges related to brain maturation, analysis methods, and the potential for motion artifacts. We review these methodological considerations and provide recommendations for best practices for each of these topics.
The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and (123)I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.
Ketamine is widely used in pediatric anesthesia. Recent studies have demonstrated that excessive application of ketamine leads to cortical neurodegeneration in neonatal brains. The present study aims to characterize the functional role of neuronal microRNA, miR-124, in regulating ketamine-induced neurotoxicity in mouse hippocampus.
Real-time quantitative PCR (RT-PCR) was used to examine the effect of high-dosage ketamine on the expression of miR-124 in murine hippocampus in vitro. Downregulation of hippocampal miR-124 was achieved by lentivirual transfection, and its effects on protecting ketamine-induced hippocampal neurodegeneration were examined both in vitro and in vivo.
Hippocampal miR-124 was upregulated by ketamine treatment. Knocking down miR-124 in vitro reduced ketamine-induced apoptosis in hippocampal CA1 neurons, upregulated AMPA receptors phosphorylation and activated the protein kinase C/extracellular signal-regulated kinases (PKC/ERK) pathway. In the in vivo Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice subjected to hippocampal miR-124 inhibition showed improved memory performance.
Our study demonstrated that miR-124 played an important role in regulating ketamine-induced hippocampal neurodegeneration. Inhibiting miR-124 may provide a molecular target to improve memory performance in both human and animals suffering from overanesthetizing-related neurotoxicity.
Abstract We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the CNS, the patient presented with a left mesiotemporal EEG focus and left hippocampal sclerosis. This is the first case which reports an association between mesial temporal lobe epilepsy and SCA13. This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies.
Thirty-five elderly women in excellent health received a neuropsychological battery and resting electroencephalograms (EEGs) from bilateral parietal scalp electrodes. Spectral density analysis of the EEGs was designed to evaluate two levels each of slow activity (delta, 0.2-3.8 Hz and theta, 4.0-7.8 Hz), alpha activity (slow alpha, 7.0-9.8 Hz and fast alpha, 10.0-12.8 Hz) and fast activity (sigma, 13.2-14.8 Hz and beta, 15.0-20.0 Hz). There was no relationship between alpha slowing and cognitive impairment. However, significant correlations emerged between sigma activity and Wechsler Adult Intelligence Scale Scores. This association was strongest between right parietal sigma activity and WAIS Performance Scale weighted scores.
The hand preference items included into 8.
Chapman L. J., Chapman J. P. The measurement of handedness. Brain and Cognition 1987; 6: 175–183View all references inventory were comparatively assessed concerning the frequencies of the answers given by Bulgarian right, mixed, and left handers, concerning the correlation of each item with the remaining 12, with eyedness and footedness scores. Relationships between writing hand, throwing hand, eyedness, and footedness were studied. Application of a cumulative index of familial sinistrality evidenced the biological significance of the main findings. All the results showed the inferiority of the writing hand as compared to the remaining items and evidenced the full inappropriateness of this item as a single predictor of handedness.
ABSTRACT The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders, among which SCA subtype 13 (SCA13) was found associated with mutations in the KCNC3 gene. Among 522 Chinese Han SCA patients (including familial and sporadic) we have collected since 1995, approximately 40% of them have not yet been assigned genotype. To investigate the mutation frequency of KCNC3 in SCA patients from mainland Chinese Han population, we analyzed the KCNC3 gene in 201 unrelated patients diagnosed with dominantly inherited cerebellar ataxia using the denaturing high-performance liquid chromatography (DHPLC) method. All analyzed samples displayed the normal elution profile, which denoted that no disease-related mutation was identified, suggesting that SCA13 be a rare form of SCA in mainland China.
The differential representation of the toes/feet and fingers/hands along the medial and lateral surfaces of the cerebral cortices, respectively, may have diagnostic utility. Normative data for errors for toe and finger graphaesthesia and gnosis, as well as foot and finger agility, were collected for 86 children (ages 7 to 14). The fingers were more agile than the feet, and the right side of the body was more agile than the left side, regardless of age. A marked improvement in toe gnosis, but not in finger gnosis occurred in children after 11-12 years of age. A statistically significant interaction between laterality and gender was due to the greater numbers of errors for both toe and finger gnosis, displayed by girls for the left sides of their bodies compared to their right sides. This discrepancy was not significant for boys.
The cobalt model of epilepsy, in combination with the C-14 2-deoxyglucose (2-DG) autoradiographic technique, was used to assess the effects of phenytoin (PHT) and ethosuximide (ESM), two antiepileptic drugs, and ketamine (KET), a drug with anticonvulsant properties, on brain activity. Nine days after the unilateral insertion of a cobalt rod into visual cortex, the nondrugged control rats showed the usual hypermetabolic regions of putative epileptogenic tissue both adjacent to the necrotic cortical cobalt rod implant zone and more distally in the connecting thalamus. PHT and ESM, given a single injections immediately before the 2-DG uptake and clearing period, diminished glucose uptake in the cobalt-induced hypermetabolic "patches" as well as in normal tissue. However, both drugs decreased 2-DG uptake more in the thalamic patches, than in the less hypermetabolic cortical patches, where the drug-induced depression in glucose metabolism was the same as for normal tissue. These findings suggest that PHT and ESM, regardless of their actions on cell receptors and membrane conductances, are ultimately of therapeutic value because more active nervous tissue (such as epileptic tissue) is more vulnerable to the depressing effects of these drugs than is less active tissue. KET, in contrast to PHT and ESM, did not depress metabolic activity throughout the brain generally and even clearly increased it in limbic system structures. Also in contrast to PHT and SEM, KET diminished activity in the cobalt-induced patches without reducing it in the normal tissue of the homotopic control regions. The more selective depressing action of KET, an N-methyl-D-aspartate (NMDA) antagonist, may be related to the role NMDA receptors play in supporting strong nervous activity. The discussion emphasizes the usefulness of a combined cobalt/2-DG approach to antiepileptic drug assessment.
14-3-3 proteins and tissue damage association were determined. The localization of 14-3-3 proteins in section of cortex from ischemia produced rats was examined by immunohistochemistry. Ischemia was produced in rats by unilaterally clamping the carotid artery for 6 hrs at the distal side. Following recovery for 6 hrs, the animals were sacrificed. The intensity of neuronal necrosis stained with antibody raised against 14-3-3 protein was markedly more in the cortex than the other parts of the brain, since there was occlusion of the artery which feeds this region. 14-3-3 antibody was confined to neuronal cell body. Since 14-3-3 proteins are central to mitogen-activated protein (MAP) kinase signaling, this pathway is in part responsible for the hyperphosphorylation of neurofilaments or cytoskeletal proteins of neuron, which may possibly lead to neuronal inclusions.
Edaravone, a free radical scavenger, has shown neuroprotection properties in both animals and humans. To evaluate the mechanisms involved, we obtained a culture of almost pure neurons. The neurons, either untreated or prophylactically treated with edaravone, were exposed to 300 μM hydrogen peroxide. We examined alterations in mitochondria, the percent of apoptotic cells and the immunoblots of key regulatory proteins, and the protein-protein interactions and the cellular locations of cytochrome c. The levels of p-JNK (Thr183/Tyr185) and cytochrome c in cytosol and BAX in heavy membrane (HM), respectively, were increased at 0.5 h and reached the peak at 12 h after stimulation with hydrogen peroxide. The levels of p-BAD and BAX in the cytosol and the interaction between BAD and 14-3-3 were decreased in the untreated neurons. However, edaravone could prevent these changes. In addition, mitochondrial morphology was better preserved and the percentage of apoptosis was lower under the treatment with edaravone. In summary, the present study indicates that edaravone could protect neurons by inhibiting: (1) the activity of JNK, (2) the disassociation of BAD from 14-3-3, and (3) the translocation of BAX from cytosol to mitochondria.
The pathology of relapsing-remitting multiple sclerosis (RR-MS) is largely attributed to activated autoreactive effector T lymphocytes. The influence of microRNAs on the immune response has been shown to occur in different pathways of lymphocyte differentiation and function. Here, the expression of the miRNAs miR-15a/16-1 in PBMC, CD4(+), and CD8(+) from RR-MS patients has been investigated. BCL2, a known miR-15a/16-1 target, has also been analyzed. The results have shown that miR-15a/16-1 is downregulated in CD4(+) T cells, whereas BCL2 is highly expressed in RR-MS patients only. Our data suggest that miR-15a/16-1 can also modulate the BCL2 gene expression in CD4(+) T cells from RR-MS patients, thereby affecting apoptosis processes.
To investigate the long-term efficacy and safety of a botulinum toxin type A (BoNT-A) for the treatment of cervical dystonia (CD).
We conducted a retrospective chart review of patients with CD treated with abobotulinumtoxinA (Dysport™ 100-800 units [U] for injection) between 1993 and 2009 at the University Hospital "La Paz" (LPUH). Affected muscles were selected using electromyography (EMG).
Thirty-seven patients were included in the study; most were female (62%) and had idiopathic CD (60%). Almost half (46%) of patients were diagnosed with the condition more than 10 years ago. The most common clinical presentations of CD were rotation (46%) and laterocollis (43%). On average, patients were treated with Dysport for 7 years (range: 1-17 years) and received 487 (range: 320 to 650) U over 15.9 (range: 1 to 40) injection cycles. Most (97%) patients maintained a response from treatment initiation to end of evaluation period. Overall, 70% of patients were taking concomitant oral medication. Dysport was generally well tolerated. Dysphagia was reported by 18.9% of patients, but this did not lead to discontinuation of Dysport treatment.
These data confirm the long-term efficacy and safety of Dysport in CD over a period of up to 17 years.
The aim of this study was to determine the association between alcohol intake and risk of dementia related death, taking into account relevant confounding and mediating factors.
Materials and methods:
Data was obtained from a Norwegian prospective study with a 17-year follow-up. The study population comprised 25,635 participants aged between 60 and 80 years at the time of examination from the Cohort of Norway (CONOR). Cox regression was used to investigate the association between alcohol use and dementia related death.
Nearly half (12,139) of the study population died during follow-up, of which 1,224 had a diagnosis of dementia on their death certificate. The risk of dementia related death was significantly higher among abstainers than among individuals that drank alcohol once per month (HR = 1.33, 95% CI = 1.14-1.56, p < 0.001, in a fully adjusted model). Respondents with missing information regarding alcohol consumption (representing 5% of the study population) had the highest risk of dementia related death (HR = 1.60, 95% CI = 1.28-2.00, p < 0.001) and also significantly higher mortality rates due to alcohol-related causes (HR = 1.41, 95% CI = 1.03-1.93, p = 0.031) and other causes (HR = 1.32, 95% CI = 1.21-1.43, p < 0.001), all compared to those drinking alcohol no more than once per month.
These findings suggest that the risk of dementia related death is significantly higher among elderly abstainers than among those who drink alcohol, after adjusting for relevant confounders. However, care should be taken in interpretation of data due to missing information on drinking frequency, as this missing-group might have a large share of the heavy drinkers in the study cohort.