Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating striatum.
It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) in this experimental paradigm, we have examined its activity by assessing the accumulation of l-3,4-dihydroxyphenylalanine after inhibiting the subsequent enzyme in the DA synthetic pathway, aromatic l-amino acid decarboxylase, with 3-hydroxybenzylhydrazine. In addition the amount of TH protein was assessed by western blotting and its distribution in the CS was examined using immunohistochemical methods. 6-hydroxydopamine injection produced a significant decrease in DA levels and l-3,4-dihydroxyphenylalanine accumulation, as well as decreases in TH protein and TH immunoreactive fibres in the CS. After nicotine treatment, the decrease in TH protein in the CS was significantly reduced, with a concomitant preservation of TH activity, but nicotine did not alter the number of TH immunoreactive fibres. The activity and amount of TH did not change in the contralateral (intact) CS. Thus, nicotine induces long lasting TH plasticity in the degenerating CS. A synergistic action of nicotine-activated and lesion-originated signals appears necessary for the expression of this neuronal molecular plasticity.
Urbanavicius
Jessika
J
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Ferreira
Margot
M
Costa
Gustavo
G
Abin-Carriquiry
Juan Andrés
JA
Wonnacott
Susan
S
Dajas
Federico
F
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D018722:Nicotinic Agonists; D007980:Levodopa; D009538:Nicotine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine