Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide.
Huntington's disease (HD) results from the degeneration of striatal neurones, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic receptors (D2R). This target is expressed by about half of striatal neurones and its scintigraphic exploration has already been performed for the follow-up of this degenerative process. Ex vivo autoradiography of D2R performed with iodobenzamide, the widely used ligand for single photo emission computerized tomography, revealed slight neuroprotection. Moreover, tolerance of microspheres was demonstrated by in vitro autoradiography with the marker of gliosis, [(3)H]-PK 11195.
Gouhier
C
C
INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, Université François Rabelais, UFR des Sciences Pharmaceutiques, Tours, France. gouhier@univ-tours.fr
Chalon
S
S
Venier-Julienne
M C
MC
Bodard
S
S
Benoit
J
J
Besnard
J
J
Guilloteau
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001345:Autoradiography; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology; D001672:Biocompatible Materials; D003342:Corpus Striatum / Q000166:cytology; D003714:Denervation; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers; D006816:Huntington Disease / Q000188:drug therapy; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects*; D007457:Iodine Radioisotopes; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D020932:Nerve Growth Factor / Q000493:pharmacokinetics*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D014316:Tritium
D000970:Antineoplastic Agents; D001549:Benzamides; D001672:Biocompatible Materials; D018492:Dopamine Antagonists; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D007546:Isoquinolines; D018696:Neuroprotective Agents; D011108:Polymers; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D014316:Tritium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D020932:Nerve Growth Factor; D017378:Quinolinic Acid; C037850:PK 11195