The amazing brain

It is in the human nature to be curious about how we feel pain, see the world, hear bird`s songs, remember, forget, reason. We want to understand the nature of love, anger, satisfaction, desire and madness. This is a short story about the evolution of the science on the human brain and about major brain discoveries. It gives a concise historic perspective of the understanding of the nervous system - from ancient Egypt to the birth of Renaissance, with the works of Vesalius and his esteemed contemporaries. The contributions of 17th century neuroanatomists such as Tomas Willis followed by the pre-modern neuroscience researchers Camillo Golgi and especially Santiago Ramon y Cajal are highlighted. The contribution of transgenic mouse models and the application of modern noninvasive imaging methods such as positron emission tomography (PET) and magnetic resonance imaging (MRI) for ground braking functional studies on the human brain are briefly reviewed. Important 21st century projects such as the Human and Mouse Connectome projects and the White House Brain Initiative are also presented. Biomed Rev 2015; 26: 1-12.Key words: psychikon pneuma, census communis, NGF, PET, fMRI, connectom

Electron microscopist's view of the Alzheimer's plaque

Alzheimer's disease (AD) is characterized by extracellular aggregation and deposition of Amyloid-beta peptide in the form of diffuse and fibrillar plaques. More than 50 years ago electron microscopic studies in humans have characterized the structure of the amyloid plaque and neurofibrillary tangles. More recently animal models of AD-type amyloidosis have provided excellent opportunities to study plaque structure during the development and expression of AD-type pathology. Ultrastructural data from a variety of transgenic mice overexpressing mutant amyloid precursor proteins, mutant presenilins, with or without human ApoE knock-in isoforms, are highly comparable to classical electron microscopic findings in AD. This review is an attempt to evaluate, from an electron microscopist`s point of view, the structural identity of AD type pathology, and the mature amyloid plaque in particular.Biomedical Reviews 2012; 23: 9-17

Modeling traumatic brain injury: mechanisms of early neuronal and axon degeneration in the infant rodent brain

Traumatic brain injury (TBI) remains a major health challenge and affects the young disproportionately. Accidental and non-accidental TBI in children is a major contributor to morbidity, disability, and death. TBI in this critical period leads to profound neuronal and axonal degeneration followed by cognitive, psychological and memory impairment, altered processing speed, impaired executive functions, emotional liability as well as word finding difficulties. Cognitive and behavioral changes may remain unrecognized for periods even after sustaining mild injury. Although accidental and non-accidental inflicted injury (blunt force or violent shaking-inflicting brain injury or “Shaken baby” syndrome) posits a major clinical and sociological problem, mechanisms of tissue degeneration might be largely similar. The scope of this review will be the experimental research related to modeling blunt (concussive) head trauma specifically to the infant rodent brain resulting in acute (early) and protracted (late) degenerative changes such as axonal degeneration and apoptotic neuronal cell death. Similarly, discussion will be limited to therapeutic windows and potentials for ameliorating the development of early brain injury

Apoptosis in the mammalian nervous system: developmental and clinical implications

Among the many regulatory steps in brain development is the process of elimination of differentiating neurons at certain stages of maturation through an intrinsic suicide program now widely known as apoptosis. Apoptosis may thus describe a cell death pathway utilized by many developing cells in the nervous system, but may also be activated as a consequence of acute or chronic pathological impulses. Such pathological impulses may include brain injury, cerebral hypoxia-ischemia and the potentials of selected drugs such as N-methyl D-aspartate (NMDA) receptor antagonists, GABA mimetics and ethanol. In recent years, there has been a great interest in mechanisms of cell death in the nervous system and apoptotic cell death has been implicated in many neuro degenerative diseases such as Alzheimer's disease, amiotrophic lateral sclerosis, Parkinson's disease and other central and peripheral nervous system disorders. Recent findings have evaluated the contribution of programmed cell death and specific gene products involved in each of these cases. A deeper understanding of these processes may lead to the discovery of strategies for slowing, reducing or arresting neuronal and glial cell death induced by injury, aging or disease.Biomedical Reviews 2002; 13: 49-61

ULTRASTRUCTURE OF THE WALL OF THE TERMINAL VESSELS OF THE STOMACH MUCOSA

The infrastructure of the wall of the terminal gastric mucosa vessels (of Corpus and pars pylorica) of 15 adult rats was investigated. It was established that the number of fenestrated vessels as well as the degree of fenestration in direction to the glandular cells enhanced along with vascidar caliber increasing. While the thickness of the endothelial cells and the amount of their organelles reduced there was an elevation of the count and length of luminal evaginations. The basal membrane became thinner and the pericytes reduced in number. These alterations could be better established in the subepithelial vessels (mainly in the venous capillaries and postcapillary venules) which was more outlined in the pyloric region. The gastric mucosal veins were presented by venules without myocytes but with pericytes. Some arteries could be observed in the submucosa only. The fenestration was interpreted in the sense of possible participation in the ionic transport

NGF-PC-AD connection

In an elegant manner Viviana Triaca presented in this volume of Adipobiology her Homage to Rita Levi-Montalcini highlighting the significance of nerve growth factor (NGF) in the molecular mechanisms of Alzheimer's disease (AD). This remarkable review generates a completely new direction in understanding some of the new and specific aspect of AD pathology, focusing on the NGF modulation of amyloid precursor protein (APP) processing and metabolism. Dr Triaca provides a paradigm shift from "classical" cholinergic to NGF-centered approach showing that the dysregulation of NGF-TrkA (receptor tyrosine kinase A) and proNGF-p75NTR signaling systems is a good candidate for being primus movens in the pathogenesis of AD.Adipobiology 2013; 5: 19-22

Immunomorphological characteristics of pleomorphic adenoma of salivary glands

The immunohistochemical profile of 23 pleomorphic adenomas and 7 normal salivary glands was studied. We used antisera to vimentin (V), desmin (D), epithelial membrane antigen (EMA), prostate specific antigen (PSA), pancytokeratin, carcinoembryonic antigen (CEA), glial fibrillary acidic protein (GFAP) and S-100 protein. In the ducts and myoepithelial cells of normal salivary glands immunopositivity to most of the cytoskeletal proteins, EMA and CEA was observed. GFAP was localized only in cells of striated ducts. Major differences in the expression of various antigens among tubular structures, solid sheets, the myxoid and chondroid in the pleomorphic adenoma were encountered. Appearance of GFAP as a sign of stromal transformation into myxoid and chondroid was detected.Judging from these comparative immunohistochemical characteristics between normal salivary glands and pleomorphic adenomas, we assume that tumour cells originate from the reserve cells of intercalated and striated ducts.Nous avons étudié les caractéristiques immunohistochimiques de 23 adénomes pléomorphes et de 7 glandes salivaires non tumorales. Nous avons utilisé des anticorps pour la vimentine (V), la desmine (D), l’antigène de membrane épithéliale (EMA), antigène prostatique spécifique (PSA), la pancytokératine, l’antigène carcinoembryonnaire (CEA), la protéine gliale fibrillaire acide (GFAP) et la protéine S-100. Dans les canaux et dans les cellules myoépithéliales des glandes salivaires normales c’est l’immunopositivité pour la plupart des protéines du cytosquelette, EMA et CEA qui est observée. GFAP est localisée uniquement dans les cellules des canaux striés. Des différences majeures dans l’expression des divers antigènes ont été rencontrées dans les structures tubulaires, dans les nappes cellulaires et dans les portions myxoïdes et chondroïdes des adénomes pleomorphes. L’apparition de GFAP a été observée comme signe de transformation myxoïde ou chondroïde du stroma.En nous basant sur la comparaison des caractéristiques immunohistochimiques entre les glandes salivaires normales et les adénomes pléomorphes, nous supposons que les cellules tumorales trouvent leur origine dans les cellules de réserve des canaux intercalaires et des canaux striés.

SOS for SOC: the renaissance of a seemingly ubiquitous organelle

In this volume of Biomedical Reviews Denys Wheatley presents a short review "Rediscovery" of a forgotten organelle, the primary cilium: the root cause of a plethora of disorders. Dr Wheatley has extensively published cilium-related research papers, reviews and book chapters. Quite naturally has been an advocate for attracting scientific interest to this beautiful biological structure for decades. Therefore he is well suited to provide a world-class view on this scientific problem. He does that in an elegant manner in his review, and states the future direction of research into the ubiquitous nature and involvement of this organelle in health and disease.Biomedical Reviews 2013; 24: 9-10

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain

BACKGROUND: In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. RESULTS: Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm(3)) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. CONCLUSIONS: In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes