The Structures of the E22Δ Mutant-Type Amyloid-β Alloforms and the Impact of E22Δ Mutation on the Structures of the Wild-Type Amyloid-β Alloforms

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Structures of the E46K Mutant-Type α-Synuclein Protein and Impact of E46K Mutation on the Structures of the Wild-Type α-Synuclein Protein

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Targeting Selective Activation of M1 for the Treatment of Alzheimer’s Disease: Further Chemical Optimization and Pharmacological Characterization of the M1 Positive Allosteric Modulator ML169

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Does the presentation of Creutzfeldt-Jakob disease vary by age or presumed etiology? A meta-analysis of the past 10 years

It is not clear whether differences in symptom presentation vary by age or etiological subtype in Creutzfeldt-Jakob disease. A PubMed search was conducted using the keyword "Creutzfeldt-Jakob" and results within the last 10 years were sorted by the English language. We found that certain characteristics, such as affective illness (28.8%), present more commonly in younger patients irrespective of disease type. Young age of onset predicts presenting symptoms of affective illness, sleep disturbance, and poor concentration, as well as certain neurological symptoms, including cerebellar/gait disturbance, visual/oculomotor disturbance, sensory disorder, vertigo/dizziness, and headache.     

Influence of the Physiochemical Properties of Superparamagnetic Iron Oxide Nanoparticles on Amyloid β Protein Fibrillation in Solution

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Imaging of Superoxide Generation in the Dopaminergic Area of the Brain in Parkinson’s Disease,Using Mito-TEMPO

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Filling the evidence gap: how can we improve the outcome of neonatal encephalopathy in the next 10 years?

Neonatal encephalopathy associated with perinatal hypoxia-ischaemia is one of the most common causes of death and permanent disability worldwide. However, of a wide range of “experimentally neuroprotective treatments” invented so far, only therapeutic hypothermia has been promoted into a standard clinical practice. Such a wide gap in the efficacy of neuroprotective treatments between the experimental setting and clinical practice may be attributed to the strategic flaw in translating basic knowledge into clinical care. When previous clinical studies are carefully reviewed, one may notice that few therapeutic options were chosen based on their track records in experimental studies; protective effects of some drugs had been assumed only based on their pharmacokinetics in adult species; several therapies were chosen merely because clinicians were familiar to these treatments for other purpose; some other therapies were imported too preliminarily from laboratory to clinical practice, potentially ignoring the difference in physiological and pathological backgrounds between rodent models and human patients. When further clinical trials are planned, it is important to ask whether (i) the treatment is supported by pharmacokinetics specific to immature brain, and (ii) the neuroprotective effect of the treatment has consistently been demonstrated using clinically relevant models and study designs. The use of translational large animal models allows the practical simulation and fine-tuning of clinical protocols, which may further assist successful translation of basic knowledge. In addition to the effort to develop alternative therapeutic options, it is important to maximise the effect of the current only neuroprotective option, or therapeutic hypothermia. Independent variables which influence the efficacy of hypothermia have to be elucidated to improve its therapeutic protocol, and to increase the number of patients who will benefit from this treatment.     

Neuroprotective Effects of Lithium: Implications for the Treatment of Alzheimer’s Disease and Related Neurodegenerative Disorders

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Have the Cross-Informant Syndromes of the CBCL any practical value in identifying grouped ICD10 diagnoses?

 120 children referred to a child and adolescent psychiatric service in a university clinic were studied with the aim of deriving predictors for grouped ICD10 diagnoses using the CBCL Cross-Informant-Syndromes (CISs). CIS7 (Delinquent Behaviour) and CIS8 (Aggressive Behaviour) were shown to significantly separate Disruptive Behaviour Disorders from all other disorders. As cross-validation, a separate clinical sample of 118 children from a similar service in another part of the country was used to see to what extent the CIS predictors from the first sample held up in the second sample. Positive and Negative Predictive Powers, all corrected for chance, confirmed that the Disruptive Behaviour Disorder group could be usefully separated from all other disorders using the Delinquent Behaviour and the Aggressive Behaviour Cross-Informant Syndrome scores. There was no good evidence that Emotional (Anxiety-Mood) Disturbance could be usefully separated in the same way using the Anxious-Depressed Syndrome (CIS3) or any other syndrome. Discriminant Function Analysis showed that there was no significant improvement in prediction when more elaborate linear combinations of the syndromes were used. Accepted: 17 April 2000     

ICD-10 classification in Danish child and adolescent psychiatry--have diagnoses changed after the introduction of ICD-10?

The aim was to test this in a nationwide register study of diagnoses used in child and adolescents psychiatry in Denmark. A larger number of different diagnoses were expected to be applied after the introduction of the 10th version of the International Classification of Diseases (ICD-10). Reflecting the time trend, we particularly expected an increase in the number of neuropsychiatric diagnoses. From the Danish Psychiatric Central Register data were drawn on clinical discharge diagnoses. All patients aged 0-15 years examined at psychiatric hospitals from 1995-2002 were included; 22,469 children and adolescents with a first contact were registered. The most frequent discharge diagnoses were pervasive development disorders (PDD; 11.9%), adjustment disorders (10.6%), conduct disorder (9.5%), emotional and anxiety disorders (7.6%), hyperkinetic disorders (7.3%), and specific developmental disorders (7.3%). We found a significant increase in the number of neuropsychiatric and affective diagnoses and a significant decrease in the number of adjustment, conduct and anxiety diagnoses during the study period. Of the 22,469 diagnoses, 45% were only partly specified according to ICD-10. Thirty-four per cent had diagnoses unspecified on the four-character level (Fxx.9) and 11% had Z-diagnoses. A larger number of different diagnoses and an increase in the use of neuropsychiatric diagnoses were seen after the introduction of ICD-10. Many diagnoses were only partly specified; consequently, a more detailed specification of the ICD-10 is still required.     

What is the role of the cerebellum in the pathophysiology of dystonia?

Journal of Neurology -     

Does the place of treatment influence the quality of life of schizophrenics?

OBJECTIVE: Chronically mentally ill patients in community mental health care report a better quality of life (QOL) than those in long-term hospital care, which suggests that the treatment setting per se influences their QOL. METHOD: In a region where both treatment settings are of a comparable high standard, we assessed the QOL of 96 schizophrenic patients from these two treatment settings, and the factors which most influenced their QOL. RESULTS: Community-care patients reported a better QOL than long-term hospital-care patients. However, when other factors influencing QOL were included in a regression analysis, the place of treatment was no longer significant, but rather the social support, the severity of the illness, educational level and certain illness concepts. CONCLUSION: It is probably not the place per se which influences the QOL, but apart from personal, sociodemographic and illness-related factors, the amount of social support that is provided in different settings.     

Coenzyme Q10 Influences on the Levels of TNF-α and IL-10 and the Ratio of Bax/Bcl2 in a Menopausal Rat Model Following Lumbar Spinal Cord Injury

The roles of the immune response and apoptosis as potential mediators of secondary damage in spinal cord injury (SCI) are being investigated. Research is also being done to determine the effects of female gonadal steroids, which decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI. We hypothesized that in the absence of female gonadal steroids, which provide protection following an SCI, CoQ10 could modulate the expression of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-10, besides aquaporin-4 (AQP4) water channels in the CNS, which participate in neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in apoptosis at the site of injury. The spinal cord was compressed at the level of the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after surgery. The TNF-α and IL-10 expressions were studied using an ELISA. Western blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-α significantly decreased following the administration of CoQ10 compared with the level of IL-10. When the treatment group was compared with the OVX-SCI group, the ratio of Bax/Bcl2 significantly decreased in the groups (P?<?0.01). Based on our findings, CoQ10 could be used to compensate for the absence of the neuroprotection effects provided by female gonadal steroids via reducing the inappropriate effects of the two main pathways of secondary damage in SCI apoptosis.     

After-effects of 10 Hz tACS over the prefrontal cortex on phonological word decisions

IntroductionPrevious work in the language domain has shown that 10 Hz rTMS of the left or right posterior inferior frontal gyrus (pIFG) in the prefrontal cortex impaired phonological decision-making, arguing for a causal contribution of the bilateral pIFG to phonological processing. However, the neurophysiological correlates of these effects are unclear. The present study addressed the question whether neural activity in the prefrontal cortex could be modulated by 10 Hz tACS and how this would affect phonological decisions.MethodsIn three sessions, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the bilateral prefrontal cortex before task processing. Resting state EEG was recorded before and after tACS. We also recorded EEG during task processing.ResultsRelative to sham stimulation, 10 Hz tACS significantly facilitated phonological response speed. This effect was task-specific as tACS did not affect a simple control task. Moreover, 10 Hz tACS significantly increased theta power during phonological decisions. The individual increase in theta power was positively correlated with the behavioral facilitation after 10 Hz tACS.ConclusionOur results show a facilitation of phonological decisions after 10 Hz tACS over the bilateral prefrontal cortex. This might indicate that 10 Hz tACS increased task-related activity in the stimulated area to a level that was optimal for phonological performance. The significant correlation with the individual increase in theta power suggests that the behavioral facilitation might be related to increased theta power during language processing.     

Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-l-tryptophan Inhibitor on Alzheimer’s Aβ1–42 Dimer in Terms of Aggregation and Toxicity

l-tryptophan (NQTrp) molecule was reported to alter Aβ self-assembly and reduce toxicity. Though nuclear magnetic resonance experiments and various simulations provided atomic information about the interaction of NQTrp with Aβ peptides spanning the regions of residues 12–28 and 17–42, none of these studies were conducted on the full-length Aβ1–42 peptide. To this end, we performed extensive atomistic replica exchange molecular dynamics simulations of Aβ1–42 dimer with two NQTrp molecules in explicit solvent, by using a force field known to fold diverse proteins correctly. The interactions between NQTrp and Aβ1–42, which change the Aβ interface by reducing most of the intermolecular contacts, are found to be very dynamic and multiple, leading to many transient binding sites. The most favorable binding residues are Arg5, Asp7, Tyr10, His13, Lys16, Lys18, Phe19/Phe20, and Leu34/Met35, providing therefore a completely different picture from in vitro and in silico experiments with NQTrp with shorter Aβ fragments. Importantly, the 10 hot residues that we identified explain the beneficial effect of NQTrp in reducing both the level of Aβ1–42 aggregation and toxicity. Our results also indicate that there is room to design more efficient drugs targeting Aβ1–42 dimer against AD.     

Physiopathology of bipolar disorders: what have changed in the last 10 years?

Despite recent efforts to understand the neurobiology of Bipolar Disorder (BD), the exact pathophysiology remains undetermined. Due to the effects of various psychopharmacological agents, initial research focused on the study of biogenic amines. Recent evidence has shown that dysfunction in intracellular signaling systems and gene expression may be associated with BD. These alterations may cause interruptions in mood regulating circuits such as the limbic system, striatum and prefrontal cortex, and the neuroprotective effects of mood stabilizers may reverse this pathological process. This study aims to update the recent findings relative to the neurochemistry of BD.