Brain asymmetries related to language with emphasis on entorhinal cortex and basal forebrain

Anatomical asymmetries of the human brain are important in at least four respects: 1) they can serve as potential indicators of the evolutionary foundations of language, 2) they can be used for comparative analysis of neural specializations for communication in primates, 3) they may provide underlying structural correlates for functional imaging (fMRI, PET) and genetic studies, and finally 4) they can be used for studying disorders which are suspected to result from either disturbed development of cerebral asymmetry or asymmetric damage to the brain. In the first part of this review, we give a general framework of this field through the brief descriptions of the milestone discoveries and major conceptual advances as they emerged throughout the last 150 years. In the second part, we provide a more detailed view on the functional relevance that asymmetries of the entorhinal cortex and basal forebrain may have on the language

A Comparative Perspective on Minicolumns and Inhibitory GABAergic Interneurons in the Neocortex

Neocortical columns are functional and morphological units whose architecture may have been under selective evolutionary pressure in different mammalian lineages in response to encephalization and specializations of cognitive abilities. Inhibitory interneurons make a substantial contribution to the morphology and distribution of minicolumns within the cortex. In this context, we review differences in minicolumns and GABAergic interneurons among species and discuss possible implications for signaling among and within minicolumns. Furthermore, we discuss how abnormalities of both minicolumn disposition and inhibitory interneurons might be associated with neuropathological processes, such as Alzheimer's disease, autism, and schizophrenia. Specifically, we explore the possibility that phylogenetic variability in calcium-binding protein-expressing interneuron subtypes is directly related to differences in minicolumn morphology among species and might contribute to neuropathological susceptibility in humans

Cortical Complexity in Cetacean Brains

Cetaceans (dolphins, whales, and porpoises) have a long, dramatically divergent evolutionary history compared with terrestrial mammals. Throughout their 55–60 million years of evolution, cetaceans acquired a compelling set of characteristics that include echolocation ability (in odontocetes), complex auditory and communicative capacities, and complex social organization. Moreover, although cetaceans have not shared a common ancestor with primates for over 90 million years, they possess a set of cognitive attributes that are strikingly convergent with those of many primates, including great apes and humans. In contrast, cetaceans have evolved a highly unusual combination of neurobiological features different from that of primates. As such, cetacean brains offer a critical opportunity to address questions about how complex behavior can be based on very different neuroanatomical and neurobiological evolutionary products. Cetacean brains and primate brains are arguably most meaningfully conceived as alternative evolutionary routes to neurobiological and cognitive complexity. In this article, we summarize data on brain size and hemisphere surface configuration in several cetacean species and present an overview of the cytoarchitectural complexity of the cerebral cortex of the bottlenose dolphin

Cerebrospinal fluid phosphorylated tau proteins as predictors of Alzheimer’s disease in subjects with mild cognitive impairment

Major efforts are under way to define reliable biomarkers of Alzheimer’s disease. Highly significant increases of hyperphosphorylated tau proteins in cerebrospinal fluid have been recently reported in Alzheimer’s disease patients compared to controls by several independent groups, including ours. These findings support the notion that cerebrospinal fluid phosphorylated tau proteins may be very useful biomarkers in the early identification of Alzheimer’s disease in patients with mild cognitive impairment

Comparative organization of the claustrum: what does structure tell us about function?

The claustrum is a subcortical nucleus present in all placental mammals. Many anatomical studies have shown that its inputs are predominantly from the cerebral cortex and its outputs are back to the cortex. This connectivity thus suggests that the claustrum serves to amplify or facilitate information processing in the cerebral cortex. The size and the complexity of the cerebral cortex change dramatically over evolution. Rodents are lissencephalic, with few cortical areas, while many primates have a greatly expanded cortex and many cortical areas. This evolutionary diversity in the cerebral cortex raises several questions about the claustrum. Does its volume expand in coordination with the expansion of cortex and does it acquire new functions related to the new cortical functions? We have examined the organization of the claustrum in animals with large brains, including great apes and cetaceans. Our data suggest that the claustrum is not always a continuous structure. In monkeys and gorillas there are a few isolated islands of cells near the main body of the nucleus. In cetaceans, however, there are many isolated cell islands. These data suggest constraints on the possible function of the claustrum. Some authors propose that the claustrum has a more global role in perception or consciousness that requires intraclaustral integration of information. These theories postulate mechanisms like gap junctions between claustral cells or a syncytium to mediate intraclaustral processing. The presence of discontinuities in the structure of the claustrum, present but minimal in primates, but dramatically clear in cetaceans, argues against the proposed mechanisms of intraclaustral processing of information. The best interpretation of function, then, is that each functional subdivision of the claustrum simply contributes to the function of its cortical partner

Predictive value of cerebrospinal fluid visinin-like protein-1 levels for Alzheimer's disease early detection and differential diagnosis in patients with mild cognitive impairment

Visinin-like protein 1 (VILIP-1) recently emerged as a potential biomarker of Alzheimer's disease (AD). This neuronal calcium sensor protein previously used as a marker of acute ischemic stroke is elevated in the cerebrospinal fluid (CSF) of AD patients. The goal of this study was to assess CSF VILIP-1 potential in early AD diagnosis and in differentiating mild cognitive impairment (MCI) patients with and without risk of AD. Additionally, we tested VILIP-1 ability to differentiate AD from other primary causes of dementia, and predict the progression of AD-related cognitive decline. VILIP-1 levels were compared with five CSF AD biomarkers (t-tau, Aβ1-42, p-tau181, p-tau199, and p-tau231). VILIP-1 successfully differentiated two MCI patient groups characterized by absence or presence of pathological levels of these CSF biomarkers, except for t-tau. VILIP-1/Aβ(1-42) and VILIP-1/p-tau181 ratios also differentiated MCI patients with pathological CSF biomarker levels. However, there was no difference in VILIP-1 levels between AD and MCI patients. VILIP-1/Aβ(1-42) and VILIP-1/p-tau231 ratios reached high sensitivities (above 70%) and very high specificities (above 85%) in differentiating AD patients from HC. Additionally, VILIP-1 differentiated AD from patients with Lewy body disease with 77.1% sensitivity and 100% specificity. VILIP-1 potential as a prognostic biomarker of cognitive decline in AD was also proved since VILIP-1/t-tau, VILIP-1/p-tau181, and VILIP-1/p-tau231 ratios correlated with MMSE scores. These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD

Human neuroblastoma SH-SY5Y cells treated with okadaic acid express phosphorylated high molecular weight tau-immunoreactive protein species

Background: Early stages of Alzheimer's disease (AD) are characterized by high phosphorylation of microtubule-associated protein tau, which may result from the downregulation of protein phosphatases. ----- New method: In order to model phosphatase downregulation and analyze its effect on tau aggregation in vitro, we treated neuroblastoma SH-SY5Y cells with okadaic acid (OA), a protein phosphatase inhibitor, and examined high molecular weight phospho-tau species. ----- Results and comparison with existing methods: OA treatment led to the appearance of heat-stable protein species with apparent molecular weight around 100 kDa, which were immunoreactive to anti-tau antibodies against phosphorylated Ser202 and Ser396. As these high molecular weight tau-immunoreactive proteins (HMW-TIPs) corresponded to the predicted size of two tau monomers, we considered the possibility that they represent phosphorylation-induced tau oligomers. We attempted to dissociate HMW-TIPs by urea and guanidine, as well as by alkaline phosphatase treatment, but HMW-TIPs were stable under all conditions tested. These characteristics resemble properties of certain sodium dodecyl sulfate (SDS)-resistant tau oligomers from AD brains. The absence of HMW-TIPs detection by anti-total tau antibodies Tau46, CP27 and Tau13 may be a consequence of epitope masking and protein truncation. Alternatively, HMW-TIPs may represent previously unreported phosphoproteins cross-reacting with tau. ----- Conclusions: Taken together, our data provide a novel characterization of an OA-based cell culture model in which OA induces the appearance of HMW-TIPs. These findings have implications for further studies of tau under the conditions of protein phosphatase downregulation, aiming to explain mechanisms involved in early events leading to AD

Анализ возможности использования борсодержащих материалов в транспортных упаковках с РАО

Выпускная квалификационная работа включает в себя: 126 страниц, 43 рисунка, 24 таблицы, 5 приложений.Объектом исследования является тетраборид вольфрама. Цель работы – проведение многоступенчатого анализа возможности применения тетраборида вольфрама в качестве материала для усиления радиационной защиты контейнеров для транспортировки и хранения РАО. В процессе исследования были изучены инженерные и программные методы расчёта ослабления потоков радиационных частиц, проанализированы различные защитные материалы с точки зрения ослабления проходящего через них ионизирующего излучения. В результате исследования получены подробные данные о радиационно-защитных характеристиках тетраборида вольфрама. Степень внедрения: высокая. Область применения: ядерная промышленность.Final qualifying work includes: 126 pages, 43 drawings, 24 tables, 5 prilozheniy.Obektom study is tetraborid tungsten. Purpose - to conduct analysis of the possibility of using multi-tetraborida tungsten as a material for strengthening radiation protection container for transportation and storage of radioactive waste. During the research were studied engineering and software methods for calculating the attenuation of radiation particles flows analyzed various protective materials from the standpoint of weakening passing through them to ionizing radiation. The study detailed data on radiation protection characteristics of tungsten tetraborida. Degree of implementation: high. Scope: the nuclear industry

A novel approach to non-biased systematic random sampling : a stereologic estimate of Purkinje cells in the human cerebellum

Non-biased systematic sampling using the principles of stereology provides accurate quantitative estimates of objects within neuroanatomic structures. However, the basic principles of stereology are not optimally suited for counting objects that selectively exist within a limited but complex and convoluted portion of the sample, such as occurs when counting cerebellar Purkinje cells. In an effort to quantify Purkinje cells in association with certain neurodegenerative disorders, we developed a new method for stereologic sampling of the cerebellar cortex, involving calculating the volume of the cerebellar tissues, identifying and isolating the Purkinje cell layer and using this information to extrapolate non-biased systematic sampling data to estimate the total number of Purkinje cells in the tissues. Using this approach, we counted Purkinje cells in the right cerebella of four human male control specimens, aged 41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells, respectively. The precision of the method is seen when comparing the density of the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3, respectively. Prior literature documents Purkinje cell counts ranging from 14.8 to 30.5 million cells. These data demonstrate the accuracy of our approach. Our novel approach, which offers an improvement over previous methodologies, is of value for quantitative work of this nature. This approach could be applied to morphometric studies of other similarly complex tissues as well