PURPOSE: Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this human neurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. MATERIALS AND METHODS: By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A(2A) and dopamine D(2) receptors) together with the degree of microglia activation. RESULTS: Both approaches showed a loss of adenosine A(2A) and dopamine D(2) receptors paralleled by an increase of microglial activation. CONCLUSION: This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to human patients.
PURPOSE:Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this humanneurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. MATERIALS AND METHODS: By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A(2A) and dopamine D(2) receptors) together with the degree of microglia activation. RESULTS: Both approaches showed a loss of adenosine A(2A) and dopamine D(2) receptors paralleled by an increase of microglial activation. CONCLUSION: This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to humanpatients.
Authors: R M Moresco; C Loc'h; M Ottaviani; B Guibert; V Leviel; M Maziere; F Fazio; B Maziere Journal: Nucl Med Biol Date: 1999-01 Impact factor: 2.408
Authors: R J Gordon; A S Tattersfield; E M Vazey; A P Kells; A L McGregor; S M Hughes; B Connor Journal: Neuroscience Date: 2007-04-24 Impact factor: 3.590
Authors: P D Callaghan; C A Wimberley; G L Rahardjo; P J Berghofer; T Q Pham; T Jackson; D Zahra; T Bourdier; N Wyatt; I Greguric; N R Howell; R Siegele; Z Pastuovic; F Mattner; C Loc'h; M C Gregoire; A Katsifis Journal: Eur J Nucl Med Mol Imaging Date: 2014-09-18 Impact factor: 9.236
Authors: S Lavisse; K Inoue; C Jan; M A Peyronneau; F Petit; S Goutal; J Dauguet; M Guillermier; F Dollé; L Rbah-Vidal; N Van Camp; R Aron-Badin; P Remy; P Hantraye Journal: Eur J Nucl Med Mol Imaging Date: 2014-12-09 Impact factor: 9.236
Authors: Yan Li; Amanda R Eskelund; Hua Zhou; David P Budac; Connie Sánchez; Maria Gulinello Journal: Int J Mol Sci Date: 2015-07-03 Impact factor: 5.923