Increased expression of Aquaporin 4 in the rat hippocampus and cortex during trimethyltin-induced neurodegeneration

Trimethyltin chloride (TMT) is a neurotoxicant producing neuronal degeneration and reactive astrogliosis in the mammalian central nervous system, especially the hippocampus. A previous magnetic resonance imaging investigation in TMT-treated rats evidenced dilation of lateral ventricles, also suggesting alterations in blood-brain barrier permeability and brain edema. Aquaporin 4 (AQP4), a glial water channel protein expressed mainly in the nervous system, is considered a specific marker of vascular permeability and thought to play an important role in brain edema (conditions). We studied AQP4 expression in the hippocampus and cerebral cortex of TMT-treated rats in order to explore the molecular mechanisms involved in brain edema occurring in these experimental conditions. Real-time PCR and western blotting data showed significant up-regulation of both AQP4 mRNA and protein levels starting 14 days after TMT treatment in the hippocampus and cortex. Parallel immunofluorescence studies indicated intense astrogliosis and AQP4 immunoreactivity diffusely pronounced in the hippocampal and cortex areas starting 14 days after TMT intoxication. In order to study the effects of TMT on vascular integrity, double-label immunofluorescence experiments for rat immunoglobulin G (IgG) and rat endothelial cell antigen-1 (RECA-1) or neuronal nuclei (NeuN) (endothelial and neuronal markers respectively) were performed. The results indicated, at 21 and 35 days after treatment, the presence of rat IgG in paravasal parenchyma and in some neuronal cells of the hippocampus and cortex. The extravasated IgG staining was temporally correlated with over-expression of neuronal vascular endothelial growth factor (VEGF) and the active phosphorylated form of its neuronal receptor (VEGFR-2P), suggesting that these factors may cooperate in mediating vascular leakage

Reelin is transiently expressed in the peripheral nerve during development and is upregulated following nerve crush

Reelin is an extracellular matrix protein which is critical for the positioning of migrating post-mitotic neurons and the laminar organization of several brain structures during development. We investigated the expression and localization of Reelin in the rodent peripheral nerve during postnatal development and following crush injury in the adult stage. As shown with Western blotting, immunocytochemistry and RT-PCR, Schwann cells in the developing peripheral nerve and in primary cultures from neonatal nerves produce and secrete Reelin. While Reelin levels are downregulated in adult stages, they are again induced following sciatic nerve injury. A morphometric analysis of sciatic nerve sections of reeler mice suggests that Reelin is not essential for axonal ensheathment by Schwann cells, however, it influences the caliber of myelinated axons and the absolute number of fibers per unit area. This indicates that Reelin may play a role in peripheral nervous system development and repair by regulating Schwann cell–axon interactions

Aquaporin 4 (AQP4) expression and blood brain barrier damage in an experimental model of neurodegeneration induced by trimethyltin

Trimethyltin (TMT) is well know

Cathepsin D Plays a Crucial Role in the Trimethyltin-Induced Hippocampal Neurodegeneration Process

Trimethyltin chloride (TMT) is known to produce neuronal damage in the rat hippocampus, especially in the CA1/CA3 subfields, together with reactive astrogliosis. Previous studies indicate that in cultured rat hippocampal neurons the Ca2 cytosolic increase induced by TMT is correlated with apoptotic cell death, although some molecular aspects of the hippocampal neurodegeneration induced by this neurotoxicant still remain to be clarified. Cathepsin D (Cat D) is a lysosomal aspartic protease involved in some neurodegenerative processes and also seems to play an important role in the processes that regulate apoptosis. We investigated the specific activity and cellular expression of Cat D in the rat hippocampus in vivo and in cultured organotypic rat hippocampal slices. The role of Cat D in cell death processes and the mechanisms controlling Cat D were also investigated. Cat D activity was assayed in hippocampus homogenates of control and TMT-treated rats. In order to visualize the distribution of Cat D immunoreactivity in the hippocampus, double-label immunofluorescence for Cat D and Neu N, GFAP, OX42 was performed. In addition, in order to clarify the possible relationship between Cat D activity, neuronal calcium overload and neuronal death processes, organotypic hippocampal cultures were also treated with a Cat D inhibitor (Pepstatin A) or Calpain inhibitor (Calpeptin) or an intracellular Ca2 chelator (BAPTA-AM) in the presence of TMT. TMT treatment in rat hippocampus induced high levels of Cat D activity both in vivo and in vitro, in glial cells and in CA3 neurons, where a marked TMT-induced neuronal loss also occurred. Cat D is actively involved in CA3 neuronal death and the protease increase is a calcium-Calpain dependent phenomeno

Aquaporin 4 expression in the rat hippocampus and cortex during trimethyltin-induced neurodegeneration

Trimethyltin (TMT) is a .....

Aquaporin 4 expression in the rat cortex and hippocampus during TMT induced neurodegeneration

Trimethyltin is an organotin.....

Aquaporin 4 expression increases in the rat hippocampus and cortex during trimrthyltin-induced neurodegeneration

Trimethyltin (TMT) ia a neurotoxicant...

Aquaporin 4 expression increases in the rat hippocampus and cortex during trimethyltin-induced neurodegeneration

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Aquaporin 4 increased expression and blood brain alteration accur in the rat hippocampus and cortex after trimethyltin intoxication

Trimethyltin (TMT) is a ....