Discriminative behavioral assessment unveils remarkable reactive astrocytosis and early molecular correlates in basal ganglia of 3-nitropropionic acid subchronic treated rats.

Abstract

Reactive astrocytosis seems to be strongly implicated in the development and maintenance of inflammatory and neurodegenerative disorders. We design a new toxic model treatment with 3-nitropropionic acid (3-NP), a mitochondrial complex II irreversible inhibitor, to induce in rats Huntington's disease (HD) like syndrome, characterized by hindlimb dystonia, involuntary choreiform movements and reduced global activity. In an attempt to find out whether molecular and morphological changes in the neuro-glial network could be involved in the pathogenesis of this disease, we developed a protocol of subchronic intra-peritoneal 3-NP intoxication. Moreover we set up specific, highly discriminative, behavioral tests to detect very early mild motor disabilities in 3-NP treated rats. This treatment did not cause severe cell death. However, in the Caudate-Putamen (CPu) of all 3-NP treated animals we found a massive astrogliosis, revealed by increased GFAP levels, paralleled by changes of the glial glutamate transporter GLAST distribution. To these glial changes we detected a transcriptional upregulation of c-fos and Sub-P in the striatal medium spiny neurons (MSN). We propose that this model of 3-NP intoxication along with the designed set of behavioral analyses allow to unmask in a very early phase the motor deficits and the underlying morpho-molecular changes associated to the onset of motor disabilities in the HD-like syndrome. Therefore this model unveil the key role played by the different components of the tripartite synapse in the pathogenesis of the HD, a putative non-cell-autonomous disease.

• Authors: Giovanni Cirillo, Nicola Maggio, Maria Rosaria Bianco, Cecilia Vollono, Stefania Sellitti, Michele Papa
• Journal: Neurochemistry international (Neurochem Int) Vol. 56 Issue 1 Pg. 152-60 (Jan 2010) ISSN: 1872-9754 [Electronic] England
• PMID: 19799953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Excitatory Amino Acid Transporter 1
• Glial Fibrillary Acidic Protein
• Neurotoxins
• Nitro Compounds
• Propionates
• Proto-Oncogene Proteins c-fos
• Slc1a3 protein, rat
• Substance P
• 3-nitropropionic acid

Topics

• Animals
• Astrocytes (drug effects, metabolism, pathology)
• Basal Ganglia (metabolism, pathology, physiopathology)
• Basal Ganglia Diseases (chemically induced, pathology, physiopathology)
• Behavior, Animal (physiology)
• Disability Evaluation
• Disease Models, Animal
• Excitatory Amino Acid Transporter 1 (drug effects, metabolism)
• Glial Fibrillary Acidic Protein (drug effects, metabolism)
• Gliosis (chemically induced, pathology, physiopathology)
• Huntington Disease (metabolism, pathology, physiopathology)
• Male
• Movement Disorders (diagnosis, pathology, physiopathology)
• Neurons (drug effects, metabolism, pathology)
• Neuropsychological Tests
• Neurotoxins (toxicity)
• Nitro Compounds (toxicity)
• Propionates (toxicity)
• Proto-Oncogene Proteins c-fos (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Substance P (drug effects, metabolism)
• Synaptic Transmission (drug effects, physiology)
• Time Factors