Dopaminergic dysfunction in neonatal hypothyroidism: differential effects of GM1 ganglioside.
The effects of daily treatment with GM1 ganglioside (30 mg/kg s.c.) from birth to day 30, on striatal pre- and postsynaptic markers of the dopaminergic system in euthyroid- and 32 day-old hypothyroid rats were studied. The purpose was to assess whether GM1 could prevent the extensive, hypothyroidism-provoked impairment of dopaminergic neurotransmission. Neonatal administration of GM1 well counteracted the hypothyroidism-related deficits in striatal synaptosomal uptake of [3H]dopamine and in membrane binding of [3H]tyramine, a putative marker for the vesicular carrier of dopamine. In the hypothyroid striatum, the decrease of concentrations of DOPAC and HVA, the loss of [3H]SCH-23,390-labelled D1-receptors and the decrease of basal- or dopamine-stimulated, D1-mediated activity of adenylate cyclase were not prevented by GM1. Although somatic and neurobehavioural aberrations of hypothyroids were not at all or only partially ameliorated, a slight improvement of the thyroid status was suggested by less decreased levels of serum thyroxine (T4) after treatment with GM1. The ganglioside-driven selective recovery of the transport and storage process of [3H]dopamine might result either from a chronically-exerted stimulation by GM1 on the NA/K- and Mg-ATPase activities, thus reflecting on the ATPase-dependent neuronal and vesicular transport processes of dopamine or from a GM1-promoted maturation of the otherwise retarded functionality of dopaminergic nerve endings in the neonatal hypothyroid striatum.
Vaccari
A
A
Department of Neuroscience, University of Cagliari, Italy.
Stefanini
E
E
de Montis
G
G
Rossetti
Z L
ZL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007037:Hypothyroidism / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D013574:Synaptosomes / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology*; D014439:Tyramine / Q000378:metabolism
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D005677:G(M1) Ganglioside; D000262:Adenylyl Cyclases; D004298:Dopamine; D006719:Homovanillic Acid; D014439:Tyramine