P2Y1 receptor switches to neurons from glia in juvenile versus neonatal rat cerebellar cortex

<p>Abstract</p> <p>Background</p> <p>In the CNS, several P2 receptors for extracellular nucleotides are identified on neurons and glial cells to participate to neuron-neuron, glia-glia and glia-neuron communication.</p> <p>Results</p> <p>In this work, we describe the cellular and subcellular presence of metabotropic P2Y₁receptor in rat cerebellum at two distinct developmental ages, by means of immunofluorescence-confocal and electron microscopy as well as western blotting and direct membrane separation techniques. At postnatal day 21, we find that P2Y₁receptor in addition to Purkinje neurons, is abundant on neuronal specializations identified as noradrenergic by anatomical, morphological and biochemical features. P2Y₁receptor immunoreactivity colocalizes with dopamine β-hydroxylase, tyrosine hydroxylase, neurofilament light chain, synaptophysin and flotillin, but not with glial fibrillary acidic protein for astrocytes. P2Y₁receptor is found enriched in membrane microdomains such as lipid rafts, in cerebellar synaptic vesicles, and is moreover visualized on synaptic varicosities by electron microscopy analysis. When examined at postnatal day 7, P2Y₁receptor immunoreactivity is instead predominantly expressed only on Bergmann and astroglial cells, as shown by colocalization with glial fibrillary acidic protein rather then neuronal markers. At this age, we moreover identify that P2Y₁receptor-positive Bergmann fibers wrap up doublecortin-positive granule cells stretching along them, while migrating through the cerebellar layers.</p> <p>Conclusion</p> <p>Membrane components including purinergic receptors are already known to mediate cellular contact and aggregation in platelets. Our results suggesting a potential role for P2Y₁protein in cell junction/communication and development, are totally innovative for the CNS.</p

Synaptic P2X7 and oxygen/glucose deprivation in organotypic hippocampal cultures.

The P2X7 receptor for extracellular ATP is the main candidate, among P2 receptors, inducing cell death in the immune system. Here, we demonstrate the direct participation of this receptor to cell damage induced by oxygen/glucose deprivation, in the ex vivo model of organotypic hippocampal cultures. By pharmacological and immunological approaches, we show that P2X7 is rapidly and transiently up regulated in hippocampal areas eliciting metabolism impairment. Moreover, the P2 antagonists 2′,3′,-dialdehyde ATP and reactive blue 2 prevent both up regulation of this receptor and hypoxic/hypoglycemic damage. By confocal laser microscopy, we show that P2X7 is present at the synaptic level of fibers extending from the CA1–2 pyramidal cell layer throughout the strata oriens and radiatum, but absent on oligodendrocytes, astrocytes or neuronal cell bodies. Colocalization of P2X7 is obtained with neurofilament-L protein and with synaptophysin, not with myelin basic protein, glial fibrillary acidic protein or a marker for neuronal nuclei. P2X7 up regulation and diffuse cellular damage are also induced by 3′-O-(4-benzoyl) benzoyl-ATP, an agonist selective but not exclusive for P2X7. In summary, our study demonstrates that P2X7 not only directly participates to the hypoxic/hypoglycemic process, but also owns specific phenotypic localization. We do not exclude that it might serve as a sensor of dysregulated neuronal activity and ATP release, both occurring during oxygen/glucose deprivation

Comparison between early-onset and late-onset alzheimer's disease patients with amnestic presentation: CSF and 18F-FDG PET study

BACKGROUND/AIMS To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). METHODS Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of AΒ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. RESULTS As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. CONCLUSIONS The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe

Development and significance of the frailty concept in the elderly: a possible modern view

Frailty is an evolving concept that is generally defined in biomedical or psychosocial terms. It is not necessarily related to a specific single disease process. Passing by the theories of Selye (1936) on the exhaustion of the General Adaptation Syndrome,until reaching to the studies of Fried (2001) who, firstly, proposed diagnostic criteria for frailty, in this paper are explored different ways to understand this concept, until endeavour to give a possible modern view. The definition of a frailty syndrome characterized by a multi-system reduction in ?reserve capacity? remains widely accepted

Sundowning syndrome: a possible marker of frailty in Alzheimer's disease?

The term "sundowning" describes a clinical phenomenon characterized by late afternoon exacerbation of behavioural symptoms in dementia. Beyond this clinical definition, the debate around this concept is not properly solved, because many authors define it in different ways, mentioning various hypothetical etiological explanations. It represents a concrete problem, which is difficult to manage for physicians and caregivers, and is probably linked to various biological, psychological and social aspects. As recently reported, the sundowning phenomenon is a predictor of faster cognitive decline in Alzheimer's disease, and as such can represent a possible marker of frailty in this illness. This article presents an overview of the biological understanding and possible pharmacological and non-pharmacological treatment of this condition