Early effects of intrastriatal injections of quinolinic acid on microtubule-associated protein-2 and neuropeptides in rat basal ganglia

• Published in: Neuroscience Vol. 93; no. 3; pp. 843 - 853
• Main Authors: Bordelon, Y.M., Chesselet, M.-F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.1999; Elsevier
• Subjects: Animals; Basal Ganglia - metabolism; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - physiology; Cytoskeleton - drug effects; Cytoskeleton - ultrastructure; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; DNA Damage; Efferent Pathways - drug effects; Efferent Pathways - metabolism; enkephalin; Enkephalins - genetics; Enkephalins - metabolism; Excitatory Amino Acid Agonists - administration & dosage; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Agonists - toxicity; excitotoxicity; Globus Pallidus - anatomy & histology; Huntington Disease - metabolism; Huntington's disease; Injections; Male; Medical sciences; Mice; Mice, Neurologic Mutants; Microtubule-Associated Proteins - metabolism; Nerve Tissue Proteins - metabolism; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Quinolinic Acid - administration & dosage; Quinolinic Acid - pharmacology; Quinolinic Acid - toxicity; rat; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - physiology; RNA, Messenger - metabolism; striatum; substance P; Substance P - genetics; Substance P - metabolism; enkephalin; MAP-2, microtubule-associated protein 2; striatum; rat; PPT, preprotachykinin; PPE, preproenkephalin; excitotoxicity; substance P; Huntington's disease; NGS, normal goat serum; NMDA, N-methyl- d-aspartate; KPBS, potassium phosphate-buffered saline; Animal model; Rat; Toxicity; Central nervous system; Enkephalin; Neuropeptide; Opioid peptide; Degenerative disease; Nervous system diseases; Substance P; Rodentia; Huntington disease; Basal ganglion; Gene expression; Cerebral disorder; Genetic disease; Vertebrata; Mammalia; Microtubule associated protein 2; Central nervous system disease; Neurotransmitter; Excitatory aminoacid; Tachykinin; Brain (vertebrata); Extrapyramidal syndrome
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00239-0

The long-term effects of intrastriatal injections of the agonist of N-methyl- d-aspartate receptors, quinolinic acid, have been extensively characterized. Much less is known, however, about the early molecular and neurochemical changes which occur within a few hours of the toxin injection. In the present study, we have performed intrastriatal injections of low doses of quinolinic acid which induce DNA damage 10–12 h post-lesion, and selective death of striatal projection neurons two weeks later. We examined the time-course of alterations in the microtubule-associated protein 2, an early marker of cytoskeletal disruption, and enkephalin and substance P, two neuropeptides present in largely distinct subpopulations of striatal efferent neurons projecting to the globus pallidus and entopeduncular nucleus, respectively. Immunoreactivity for microtubule-associated protein 2 was decreased at the periphery of the lesion 10 h after quinolinate injection. Levels of enkephalin messenger RNA were markedly decreased as early as 6 h post-lesion; however, a significant decrease in enkephalin immunoreactivity was not observed in the globus pallidus (external pallidum) until 12 h post-injection. Levels of substance P messenger RNA were decreased 12 h post-injection in striatal neurons. However, in contrast to enkephalin immunoreactivity, immunolabeling for substance P was not significantly decreased at this time-point in the internal pallidum, a finding reminiscent of early grades of Huntington's disease. The results reveal the time-course of change in messenger RNA and peptide levels in striatal efferent neurons shortly after an excitotoxic insult. These data have implications for the interpretation of findings in post mortem brain and mouse models of Huntington's disease.