Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Neurobiol Learn Mem ; 96(2): 121-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21440650

ABSTRACT

Although tissue type plasminogen activator (tPA) and brain derived neurotrophic factor (BDNF) have been extensively described to influence brain outcomes in a number of disorders, their roles during physiological aging are poorly investigated. In the present study, we investigated whether maintenance of mice in different environmental conditions could influence age-associated changes in hippocampal tPA expression and BDNF maturation in relation with modifications of their cognitive performances. Our data indicate that maintenance in enriched housing led to a reversal of age-associated decrease in expression of hippocampal tPA. A subsequent increase in the level of mature BDNF and an improvement in emotional and spatial memories were observed. Taken together, these data suggest that the tPA-BDNF axis could play a critical role in the control of cognitive functions influenced both by the age and housing conditions.


Subject(s)
Aging/physiology , Brain-Derived Neurotrophic Factor/metabolism , Brain/physiology , Environment , Neurons/physiology , Tissue Plasminogen Activator/metabolism , Animals , Association Learning/physiology , Behavior, Animal/physiology , Conditioning, Psychological/physiology , Fear/physiology , Female , Housing, Animal , Memory/physiology , Mice
2.
Mol Neurobiol ; 42(1): 64-75, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20414816

ABSTRACT

It has long been recognised that malignant tumours favour aerobic glycolysis to generate ATP and contain abnormalities of the intrinsic, mitochondria-dependent, apoptotic pathway, suggesting the involvement of dysfunctional mitochondria in tumour pathophysiology. However, the mechanisms underlying such processes in gliomas are poorly understood. Few recent studies have evaluated mitochondrial ultrastructure and proteomics in the pathophysiology of malignant gliomas. However, aberrant energy metabolism has been reported in gliomas and mitochondrial dysfunction links to glioma apoptotic signalling have been observed. Mitochondrial structural abnormalities and dysfunction in malignant gliomas is a neglected area of research. Definition of abnormalities in mitochondrial proteomics, membrane potential regulation, energy metabolism and intrinsic apoptotic pathway signalling in gliomas may open novel therapeutic opportunities.


Subject(s)
Brain Neoplasms/physiopathology , Glioma/physiopathology , Mitochondria/pathology , Animals , Apoptosis , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Energy Metabolism , Glioma/metabolism , Glioma/pathology , Humans , Mitochondria/metabolism
3.
J Cereb Blood Flow Metab ; 29(6): 1146-58, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19367295

ABSTRACT

Few data are available on the involvement of brain microvascular endothelial cells (BMECs) in excitotoxic neonatal brain lesions. Therefore, we developed an original approach for investigating mouse-derived BMECs in vitro. We hypothesized that newborn and adult BMEC cultures would show age-related differences in phenotype and sensitivity to glutamate. Expression of the monocarboxylate transporter, MCT1, was higher in neonatal than in adult BMECs, whereas expression of the glucose transporter, GLUT1, was higher in adult than in neonatal BMECs that overexpressed the N-methyl-D-aspartate receptor NR1 subunit (NMDAR1) compared with adult BMECs. The ability of neonatal and adult BMECs to be activated by glutamate was confirmed through intracellular calcium ([Ca2+]i) recording. The glutamate-induced [Ca2+]i increase was blocked by the selective NMDAR antagonist, MK-801. Significant glutamate-evoked concentration-dependent release of tissue-type plasminogen activator (t-PA) and matrix metalloproteinases (MMPs) activities was found in supernatants of neonatal, but not in adult BMECs. The glutamate-mediated release of t-PA, MMP-2, and MMP-9 proteolytic activities in neonatal BMECs was blocked by MK-801. Conceivably, this protease release from neonatal BMECs may participate in neonatal brain lesions.


Subject(s)
Aging/physiology , Brain/blood supply , Brain/enzymology , Endothelial Cells/drug effects , Endothelial Cells/enzymology , Glutamic Acid/pharmacology , Microvessels/enzymology , Animals , Animals, Newborn , Biomarkers , Brain/cytology , Brain/drug effects , Cell Shape , Cells, Cultured , Endothelial Cells/cytology , Endothelial Cells/metabolism , Excitatory Amino Acid Transporter 2/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Microvessels/cytology , Microvessels/drug effects , Microvessels/metabolism , Monocarboxylic Acid Transporters/metabolism , Phenotype , Protein Subunits/genetics , Protein Subunits/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Symporters/metabolism , Tissue Culture Techniques
4.
Cell Tissue Res ; 336(2): 249-66, 2009 May.
Article in English | MEDLINE | ID: mdl-19259702

ABSTRACT

We have investigated the distribution of oxytocin/vasopressin (OT/VP) superfamily peptides in the central nervous system (CNS) of the cuttlefish, Sepia officinalis, by using antibodies raised against mammalian OT and VP. Several populations of OT-like and VP-like immunoreactive cell bodies and fibers were widely distributed in cerebral structures involved in learning processes (vertical lobe complex, optic lobes), behavioral communication (peduncle, lateral basal and chromatophore lobes), feeding behavior (inferior frontal, brachial and buccal lobes), sexual activity (dorsal basal, subpedunculate, olfactory lobes), and metabolism (visceral lobes). The two most remarkable findings of this study were the occurrence of OT-like immunoreactivity in many amacrine cells of the vertical lobe and the dense accumulation of VP-like immunoreactive cell bodies in the subpedunculate 1 lobe. No double-immunolabeled cell bodies or fibers were found in any lobes of the CNS, indicating, for the first time in a decapod cephalopod mollusc, the existence of distinct oxytocinergic-like and vasopressinergic-like systems. The widespread distribution of the immunoreactive neurons suggests that these OT-like and VP-like peptides act as neurotransmitters or neuromodulators.


Subject(s)
Central Nervous System/metabolism , Oxytocin/immunology , Sepia/metabolism , Vasopressins/immunology , Amino Acid Sequence , Animals , Central Nervous System/anatomy & histology , Central Nervous System/cytology , Mice , Molecular Sequence Data , Nerve Fibers/metabolism , Oxytocin/chemistry , Vasopressins/chemistry
5.
J Cell Sci ; 121(Pt 20): 3357-65, 2008 Oct 15.
Article in English | MEDLINE | ID: mdl-18796535

ABSTRACT

The balance between tissue-type plasminogen activator (tPA) and one of its inhibitors, neuroserpin, has crucial roles in the central nervous system, including the control of neuronal migration, neuronal plasticity and neuronal death. In the present study, we demonstrate that the activation of the transforming growth factor-beta (TGFbeta)-related BMPR-IB (also known as BMPR1B and Alk6)- and Smad5-dependent signalling pathways controls neuroserpin transcription. Accordingly, we demonstrate for the first time that anti-Mullerian hormone (AMH), a member of the TGFbeta family, promotes the expression of neuroserpin in cultured neurons but not in astrocytes. The relevance of these findings is confirmed by the presence of both AMH and AMH type-II receptor (AMHR-II) in brain tissues, and is supported by the observation of reduced levels of neuroserpin in the brain of AMHR-II-deficient mice. Interestingly, as previously demonstrated for neuroserpin, AMH protects neurons against N-methyl-D-aspartate (NMDA)-mediated excitotoxicity both in vitro and in vivo. This study demonstrates the existence of an AMH-dependent signalling pathway in the brain leading to an overexpression of the serine-protease inhibitor, neuroserpin, and neuronal survival.


Subject(s)
Anti-Mullerian Hormone/metabolism , Brain/metabolism , Neurons/metabolism , Neuropeptides/metabolism , Receptors, Peptide/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Serpins/metabolism , Signal Transduction/physiology , Animals , Anti-Mullerian Hormone/genetics , Astrocytes/cytology , Astrocytes/metabolism , Bone Morphogenetic Protein Receptors, Type I/genetics , Bone Morphogenetic Protein Receptors, Type I/metabolism , Brain/cytology , Cell Survival/physiology , Male , Mice , Mice, Knockout , Neurons/cytology , Neuropeptides/genetics , Receptors, Peptide/genetics , Receptors, Transforming Growth Factor beta/genetics , Serpins/genetics , Smad5 Protein/genetics , Smad5 Protein/metabolism , Neuroserpin
6.
Neurobiol Dis ; 27(2): 164-73, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17566751

ABSTRACT

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder in the ageing population. It is characterized by the cerebral accumulation of toxic amyloid-beta peptide assemblies (Abeta). The serine protease plasmin, which is generated from the inactive zymogen plasminogen through its proteolytic cleavage by tissue- (tPA) or urokinase-type plasminogen activator, has been implicated in the catabolism of Abeta peptides. In this report, we studied the regulation of tPA activity in vivo during ageing in normal mice and in a mouse model of AD characterized by an exacerbated endogenous Abeta accumulation. We observed that cerebral tPA activity was decreased during ageing in normal mice and that this effect was worsened in mice overproducing Abeta peptides. These phenomena result, respectively, from a decrease in tPA expression and from an increase in the production of one of the tPA inhibitors, the plasminogen activator inhibitor type 1 (PAI-1). A similar study in sporadic AD and age-matched control brain tissues revealed that the tPA proteolytic activity was negatively correlated to Abeta peptides levels supporting the data observed in mice. Altogether, our data support a model in which amyloid deposition induces a decrease in tPA activity through the overproduction of PAI-1 by activated glial cells.


Subject(s)
Aging/physiology , Alzheimer Disease/enzymology , Amyloid beta-Peptides/metabolism , Brain/enzymology , Tissue Plasminogen Activator/metabolism , Animals , Brain/pathology , Enzyme-Linked Immunosorbent Assay , Humans , Immunohistochemistry , Mice , Mice, Transgenic , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction
SELECTION OF CITATIONS
SEARCH DETAIL
...