The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption

A major feature of Alzheimer's disease (AD), a late-onset neurodegenerative disorder, is the ordered aggregation of the β-amyloid peptide (Aβ) into fibrils that comprise extracellular neuritic plaques found in the disease brain. One of many potential pathways for Aβ toxicity may be modulation of lipid membrane function. Here, we show by in situ atomic force microscopy (AFM) that astrocyte secreted lipoprotein particles (ASLPs) containing different isoforms of apolipoprotein E (apoE), of which the apoE4 allele is a major risk factor for the development of AD, can protect total brain lipid extract bilayers from Aβ(1-40) induced disruption. The apoE4 allele was less effective in protecting lipid bilayers from disruption compared with apoE3. Size analysis of apoE-containing ASLPs and mechanical studies of bilayer properties revealed that apoE-containing ASLPs modulate the mechanical properties of bilayers by acquiring some bilayer components (most likely cholesterol and/or oxidatively damaged lipids). Measurement of bilayer mechanical properties was accomplished with scanning probe acceleration microscopy (SPAM). These measurements demonstrated that apoE4 was also less effective in modulating mechanical properties of bilayers in comparison with apoE3. This ability of apoE to alter the mechanical properties of lipid membranes may represent a potential mechanism for the suppression of Aβ(1-40) induced bilayer disruption.     

Meningoencephalitis caused by Lactobacillus plantarum – case report

Specific strains of Lactobacillus spp. are widely used as probiotic agents but it has been repeatedly reported that may have a pathogenic potential. We present the report on a case of meningoencephalitis caused by Lactobacillus plantarum in a 63-year-old man with newly diagnosed metastatic planoepitheliale lung cancer. The patient was hospitalised due to newly diagnosed cancer and during the course of hospitalisation developed symptoms of neuroinfection. On the basis of the symptoms and results of the conducted tests the patient was diagnosed with bacterial meningoencephalitis. In microbiological tests of the blood and cerebrospinal fluid L. plantarum was cultured. During the course of antibiotic therapy the patient’s condition improved. Lactobacilli are now recognised as a causative agent of infection, most notably bacteraemia. To our knowledge, this is the fourth documented case of Lactobacillus-associated neuroinfection, and only the second in an adult. Lactobacilli cause mostly opportunistic infections in immunocompromised individuals.     

Cell degeneration induced by amyloid-β peptides

Extracellular accumulation of amyloid-beta (Abeta) peptide and death of neurons in brain regions involved in learning and memory, particularly the cortex and the hippocampus, are central features of Alzheimer's disease (AD). Neuronal Ca2+ overload and apoptosis are known to occur in AD. Abeta might play a role in disrupting Ca2+ homeostasis, and this AD-associated amyloidogenic peptide has been reported to induce apoptotic death in cultured cells. However, the specific intracellular signaling pathways by which Abeta triggers cell death are not yet well defined. This article provides evidence for the involvement of mitochondrial dysfunction in Abeta-induced toxicity and for the role of mitochondria in apoptosis triggered by Abeta. In addition, the endoplasmic reticulum (ER) seems to play a role in Abeta-induced apoptotic neuronal death, the ER stress being mediated by the perturbation of ER Ca2+ homeostasis. It is likely that a better understanding of how Abeta induces neuronal apoptosis will lead to the identification of potential molecular targets for the development of therapies for AD.     

A few thoughts on “What is a seizure?”

This article is part of a Supplementary Special Issue entitled The Future of Automated Seizure Detection and Prediction.     

“Habit” gambling behaviour caused by ischemic lesions affecting the cognitive territories of the basal ganglia

We report the case of a patient suffering from sudden apathy and pathological gambling-like behaviour after bilateral ischemic lesions involving the dorsal portion of the head of the caudate nuclei and adjacent anterior limb of the internal capsules. This is the first report of the association of an apathy and abnormal gambling behaviour following a stroke affecting sub-cortical structures. Although the location of the lesions, affecting the dorsal striatum, may explain the emergence of an apathetic state, it is, however, at first sight, not easy to explain the gambling behaviour because the patient was normal in tests evaluating sensitivity to reward, and no radiological abnormality was found in the cortical-sub-cortical system of reward. It is proposed that, for this patient, the mechanism of maladaptive gambling behaviour was the development of a routine behaviour related to the patient’s cognitive inertia, a mechanism different from the changes in reward sensitivity observed after damage to the orbital ventral prefrontal–ventral striatum system or in dopamine dysregulation syndrome in Parkinson’s disease.     

Atonic seizures in children with surgically remediable epilepsy: a motor system seizure phenotype?

Aim. Atonic seizures are common in some epileptic syndromes beginning in infancy or early childhood but they are rarely described in epilepsy with focal seizures of structural aetiology. We aimed to characterize the electroclinical features of atonic seizures in surgically remediable paediatric patients and to study the spatiotemporal organization of the underlying epileptogenic networks. Methods. We retrospectively analysed two consecutive, longitudinally evaluated and surgically treated paediatric patients presenting with atonic seizures as a manifestation of pharmacoresistant epilepsy of structural aetiology, evidenced by scalp‐ and stereotactic intracerebral video‐EEG‐recordings. A quantitative analysis of the epileptogenic zone organization was performed using the “epileptogenicity index”. Results. Long‐lasting generalized ictal atonia, occurring in infancy, was a predominant clinical feature in both patients, with some hints of focal origin present in one case. The seizure phenotype evolved at later age into subtle segmental atonia, associated with prominent positive motor signs. The epileptogenic zone was localized within the dorsolateral or mesiolateral premotor region. Its spatial organization was focal, matching the lesional cortex in one and distributed involving several lesional and non‐lesional structures in the other case. The emergence of atonic semiology temporally correlated with involvement of both lateral and mesial premotor, as well as primary motor areas. Conclusion. We hypothesize that atonic seizures may be considered as a motor system seizure phenotype in the setting of structural epilepsy. Complete removal of the epileptogenic area provided excellent seizure control.     

Can autophagy protect against neurodegeneration caused by aggregate-prone proteins?

Protein conformation disorders or proteinopathies are a growing family of human diseases that are characterized by the accumulation of proteins in intracellular aggregates (also known as inclusions) in specific tissues/organs. The role of aggregates in these diseases has been a subject of vigorous debate. However, irrespective of the nature(s) of the toxic species, it is desirable for cells to be able to control the levels of these toxic proteins and restrict their accumulation. Here we discuss how the autophagy-lysosome pathway may regulate protein clearance in some of the protein conformation disorders and why this pathway may represent a possible therapeutic target in such conditions.     

Gelastie seizure 一词中文译名“痴笑发作”的商榷

1957年Daly和Mulden根据希腊文gel(o)s(意为欢乐或笑)创造gelastic epilepsy 一词用于描写以发笑为主要形式的癫痫发作.Gascon和Lombroso(1971年)推荐的定义为:固定型式的病理性发笑,没有外界的诱因.Harry(2008年)指出发笑发作是不适当的、机械的或无高兴感的发作性笑.文献中描写发笑发作的性质有多种,如强烈阵发性发笑、不可控制的笑、愉快的笑、正常的笑、微笑、强迫的笑、傻笑、介于哭笑之间、嘈杂的笑、不恰当的笑、异常的笑、窘迫的笑、生疏的笑、机械的笑、不高兴的笑、抽泣的笑、面部似笑的表情等.