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

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 di...

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Published in:Neurochemistry international 2010, Vol.56 (1), p.152-160
Main Authors: Cirillo, Giovanni, Maggio, Nicola, Bianco, Maria Rosaria, Vollono, Cecilia, Sellitti, Stefania, Papa, Michele
Format: Article
Language:English
Subjects:
3-Nitropropionic acid
Animals
Astrocytes - drug effects
Astrocytes - metabolism
Astrocytes - pathology
Basal Ganglia - metabolism
Basal Ganglia - pathology
Basal Ganglia - physiopathology
Basal Ganglia Diseases - chemically induced
Basal Ganglia Diseases - pathology
Basal Ganglia Diseases - physiopathology
Behavior, Animal - physiology
Biological and medical sciences
Disability Evaluation
Disease Models, Animal
Excitatory Amino Acid Transporter 1 - drug effects
Excitatory Amino Acid Transporter 1 - metabolism
Fundamental and applied biological sciences. Psychology
Glial Fibrillary Acidic Protein - drug effects
Glial Fibrillary Acidic Protein - metabolism
Glial glutamate transporter GLAST
Gliosis - chemically induced
Gliosis - pathology
Gliosis - physiopathology
Huntington Disease - metabolism
Huntington Disease - pathology
Huntington Disease - physiopathology
Male
Movement Disorders - diagnosis
Movement Disorders - pathology
Movement Disorders - physiopathology
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Neuropsychological Tests
Neurotoxins - toxicity
Nitro Compounds - toxicity
Propionates - toxicity
Proto-Oncogene Proteins c-fos - drug effects
Proto-Oncogene Proteins c-fos - metabolism
Rats
Rats, Sprague-Dawley
Reactive astrocytosis
Severity of Illness Index
Striatum
Substance P - drug effects
Substance P - metabolism
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Time Factors
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2009.09.013