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


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.


CONCLUSIONS
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.
Moresco
R M
RM
IBFM-CNR, University of Milan Bicocca, Nuclear Medicine Department, San Raffaele Scientific Institute, Milano, Italy. moresco.rosamaria@hsr.it
Lavazza
T
T
Belloli
S
S
Lecchi
M
M
Pezzola
A
A
Todde
S
S
Matarrese
M
M
Carpinelli
A
A
Turolla
E
E
Zimarino
V
V
Popoli
P
P
Malgaroli
A
A
Fazio
F
F
D000818:Animals; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D007546:Isoquinolines / Q000493:pharmacokinetics; D007700:Kinetics; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced*; D017378:Quinolinic Acid / Q000633:toxicity; D020891:Raclopride / Q000493:pharmacokinetics / Q000494:pharmacology*; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013238:Stereotaxic Techniques
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D020891:Raclopride; D017378:Quinolinic Acid; C037850:PK 11195