Quinolinic acid induced neurodegeneration in the striatum: a combined in vivo and in vitro analysis of receptor changes and microglia activation

• Published in: European journal of nuclear medicine and molecular imaging 2008-04, Vol.35 (4), p.704-715
• Main Authors: Moresco, R. M., Lavazza, T., Belloli, S., Lecchi, M., Pezzola, A., Todde, S., Matarrese, M., Carpinelli, A., Turolla, E., Zimarino, V., Popoli, P., Malgaroli, A., Fazio, F.
• Format: Article
• Language: English
• Subjects: Animals; Brain research; Carbon Radioisotopes; Cardiology; Corpus Striatum - drug effects; Corpus Striatum - physiology; Imaging; Isoquinolines - pharmacokinetics; Kinetics; Medicine; Medicine & Public Health; Microglia - drug effects; Microglia - physiology; Nerve Degeneration - chemically induced; Neurological disorders; Nuclear Medicine; Oncology; Original Article; Orthopedics; Quinolinic Acid - toxicity; Raclopride - pharmacokinetics; Raclopride - pharmacology; Radioisotope Dilution Technique; Radiology; Rats; Rats, Wistar; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - physiology; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - physiology; Reference Values; Rodents; Stereotaxic Techniques; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-007-0651-7

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.