The differential vulnerability of striatal projection neurons in 3-nitropropionic acid-treated rats does not match that typical of adult-onset Huntington's disease.
ABSTRACT In adult-onset Huntington's disease (HD), striatal projection neurons are much more vulnerable than striatal interneurons, but even striatal projection neurons show differences in their vulnerability, with the striatal projection neurons projecting to the internal segment of the globus pallidus being the least vulnerable. Previous studies have shown that systemic chronic treatment with 3-nitropropionic acid (3NP), an inhibitor of succinate dehydrogenase, induces the preferential loss of striatal projection neurons over striatal interneurons that is characteristic of HD, which has been taken to support the hypothesis that the pathogenic defect in HD may involve impaired energy metabolism. We sought to determine whether the patterns of survival for striatal projection neurons in 4-month-old rats after chronic systemic 3NP treatment also resemble those in adult-onset HD. We assessed the projection neuron survival using neuropeptide immunolabeling of striatal efferent fibers in striatal target areas and quantified the degree of fiber loss in the striatal target areas using computer-assisted image analysis. We found that 3NP produced relatively equal loss of striatal fibers and terminals in the globus pallidus, substantia nigra, and entopeduncular nucleus, indicating a nondifferential vulnerability of striatal projection neurons to 3NP-induced impairment in energy metabolism. The results suggest that the 3NP rat model does not fully mimic adult-onset HD pathogenesis.
Article: Nerve growth factor and fibroblast growth factor prevents acute qa-excitotoxicity in rat basal forebrain[show abstract] [hide abstract]
ABSTRACT: Adult Wistar rats were treated with unilateral intrastriatal injection of quinolinic acid (QA) in one single dose of 150 nM/L. The other two group of animals were pretreated with nerve growth factor (NGF) and fibroblast growth factor (FGF), respectively. Control group was treated with 0.154 mmol/L saline solution likewise. Activity of cytochrome c oxidase (COX) was decreased in the basal forebrain of neurotrophins (NTF)-treated animals. Striatal lesions led to the loss of tonic inhibitory inputs to the globus pallidus with consequent increase changes due to transsynaptic degeneration in the basal forebrain, will be also less extensive in the NTF-treated animals.Medicine and Biology. 01/2003; 109017:88-91.