Microglia and macrophages in human glioblastomas: A morphological and immunohistochemical study.

Glioblastomas (GBMs), a type of highly malignant brain tumour, contain various macrophages/microglia that are known as tumour-associated macrophages (TAMs). These TAMs have various roles in tumour biology. Histopathological aspects of TAMs and associations with tumour growth assessed by magnetic resonance imaging (MRI) are poorly described.

GABA Receptor Subunit α3 in Network Dynamics in the Medial Entorhinal Cortex.

Layer II of the medial entorhinal cortex (MEC LII) contains the largest number of spatially modulated grid cells and is one of the first regions in the brain to express Alzheimer's disease (AD)-related pathology. The most common principal cell type in MEC LII, reelin-expressing stellate cells, are grid cell candidates. Recently we found evidence that γ-aminobutyric acid (GABA) receptor subunits show a specific distribution in MEC LII, in which GABA α3 is selectively associated with reelin-positive neurons, with limited association with the other principal cell type, calbindin (CB)-positive pyramidal neurons.

Development of Parvalbumin-Expressing Basket Terminals in Layer II of the Rat Medial Entorhinal Cortex.

Grid cells in layer II of the medial entorhinal cortex (MEC LII) generate multiple regular firing fields in response to the position and speed of an individual within the environment. They exhibit a protracted postnatal development and, in the adult, show activity differences along the dorsoventral axis (DVA). Evidence suggests parvalbumin-positive (PV) interneurons, most of which are perisomatic-targeting cells, play a crucial role in generation of the hexagonal grid cell activity pattern.

Spatiotemporal Distribution of GABA Receptor Subunits Within Layer II of Mouse Medial Entorhinal Cortex: Implications for Grid Cell Excitability.

GABAergic parvalbumin-expressing (PV+) interneurons provide powerful inhibitory modulation of grid cells in layer II of the medial entorhinal cortex (MEC LII). However, the molecular machinery through which PV+ cells regulate grid cell activity is poorly defined. PV+ interneurons impart inhibitory modulation primarily via GABA-A receptors (GABARs).

Synaptic input as a directional cue for migrating interneuron precursors.

During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron/projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue.

Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes.

Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional.

Multipotent stem cell factor UGS148 is a marker for tanycytes in the adult hypothalamus.

The present study describes for the first time the neural expression and distribution of UGS148, a protein encoded by the RIKEN cDNA63330403K07 gene that has been shown to be prominently and characteristically expressed in neural stem cells (NSCs). Based on its molecular structure, UGS148 is an intracellular protein expected to be involved in intracellular sorting, trafficking, exocytosis and membrane insertion of proteins. We demonstrate that UGS148 is highly expressed in embryonic NSCs as well as, albeit at low level, in the adult neurogenic niches, the subventricular zone and the hippocampal dentate gyrus.

Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival.

To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (<3%) based on ultrastructural characteristics and immunogold labeling for activated caspase-3.

Localization of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress.

The locus coeruleus (LC) nucleus modulates adaptive behavioral responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell.

A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat.

Several findings have indicated an involvement of dopamine in panic and defensive behaviors. The dorsolateral column of the periaqueductal gray (dlPAG) is crucially involved in the expression of panic attacks in humans and defensive behaviors, also referred to as panic-like behaviors, in animals. Although the dlPAG is known to receive a specific innervation of dopaminergic fibers and abundantly expresses dopamine receptors, the origin of this dopaminergic input is largely unknown.

Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells.

Background: Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.

Methods: We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.

Spumiform capillary basement membrane swelling: a new type of microvascular degeneration in senescent hamster.

Brain microvasculature plays a critical role in the regulation of homeostasis of neural tissues. The present study focuses on characteristic microvascular basement membrane (bm) aberrations in the midbrain periaqueductal gray matter (PAG) and their relation to aging. The PAG can be considered a caudal extension of the limbic system and is a key structure in the regulation of a myriad of autonomic and motor control functions.

Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma.

Objective: Indoleamine-2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a large cohort of endometrial carcinoma (EC) patients.

Reduced aging defects in estrogen receptive brainstem nuclei in the female hamster.

Unlabelled: The nucleus pararetroambiguus (NPRA) and the commissural nucleus of the solitary tract (NTScom) show estrogen nuclear receptor-α immunoreactivity (nuclear ER-α-IR). Both cell groups are involved in estrous cycle related adaptations. We examined in normally cycling aged hamsters the occurrence/amount/frequency of age-related degenerative changes in NPRA and NTScom during estrus and diestrus.

Effects of different small HSPB members on contractile dysfunction and structural changes in a Drosophila melanogaster model for Atrial Fibrillation.

The most common clinical tachycardia, Atrial Fibrillation (AF), is a progressive disease, caused by cardiomyocyte remodeling, which finally results in contractile dysfunction and AF persistence. Recently, we identified a protective role of heat shock proteins (HSPs), especially the small HSPB1 member, against tachycardia remodeling in experimental AF models. Our understanding of tachycardia remodeling and anti-remodeling drugs is currently hampered by the lack of suitable (genetic) manipulatable in vivo models for rapid screening of key targets in remodeling.

Regional differences in age-related lipofuscin accumulation in the female hamster brainstem.

Lipofuscin accumulation is a characteristic feature of senescent postmitotic neuronal cells but estrogen may have protecting effects by inhibiting its formation. In the present ultrastructural study, lipofuscin accumulation was studied in 2 estrogen-α-receptive brainstem areas: nucleus pararetroambiguus (NPRA) and the commissural part of the solitary tract nucleus/A2 catecholaminergic group (NTScom/A2) and compared with the estrogen-insensitive medial tegmental field (mtf), in young (23 weeks) and aged (95 weeks) female hamsters. In the aged animals, extensive intracytoplasmic lipofuscin accumulation was observed.

Microvascular changes in estrogen-α sensitive brainstem structures of aging female hamsters.

Structural neuronal plasticity is present in the nucleus para-retroambiguus (NPRA) and the commissural nucleus of the solitary tract/A2 group (NTScom/A2) in female hamsters. Both brainstem nuclei play a role in estrous cycle related autonomic adaptations. We investigated how aging affects the capillary condition in these adaptive brainstem regions.

Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease.

Enhanced myogenic constriction of mesenteric artery in heart failure relates to decreased smooth muscle cell caveolae numbers and altered AT1- and epidermal growth factor-receptor function.

Aims: We previously showed that enhanced myogenic constriction (MC) of peripheral resistance arteries involves active AT(1) receptors in chronic heart failure (CHF). Recent data suggest both transactivation of EGF receptors and caveolae-like microdomains to be implicated in the activity of AT(1) receptors. Thus, we assessed their roles in increased MC in mesenteric arteries of CHF rats.

Formation and maturation of parallel fiber-Purkinje cell synapses in the Staggerer cerebellum ex vivo.

In vivo, homozygous staggerer (Rora(sg/sg)) Purkinje cells (PCs) remain in an early stage of development with rudimentary spineless dendrites, associated with a lack of parallel fiber (PF) input and the persistence of multiple climbing fibers (CFs). In this immunocytochemical study we used cerebellar organotypic cultures to monitor the development of Rora(sg/sg) PF-PC synapses in the absence of CF innervation. Ex vivo the vesicular glutamate transporters VGluT1 and VGluT2 reactivity was preferentially localized around the Rora(sg/sg) PC soma and proximal dendrites, which are typically CF domains.

Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern.

Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum.

The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRFR2alpha is present. In the cerebellum, CRF-R2alpha has two different isoforms: a full-length form (fl) and truncated (tr).

Cerebellar heterokaryon formation increases with age and after irradiation.

Hematopoietic cells have been demonstrated to survive in many nonhematopoietic tissues after transplantation. Apparent "bone marrow-derived" cerebellar Purkinje cells in fact result from fusion events and it has been suggested that fusion may be a natural physiological phenomenon to rescue dysfunctioning cells. Here, we show that fusion of transplanted bone marrow cells with resident Purkinje cells is age-dependent and is strongly enhanced when Purkinje cells are damaged by high-dose irradiation.

The glutamate receptor delta 2 in relation to cerebellar development and plasticity.

Understanding what are the mechanisms that strengthen, stabilize and restrict synaptic innervation is a relevant topic in glutamate receptor delta 2 (GluRdelta2)-related research. It also involves targeting and selection of afferent input during formation of the neuronal circuitry in the cerebellar cortex and its functioning. This review will focus on the role of GluRdelta2, one of the main players in this field.