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The effects of neonatal thyroid deficiency on acetylcholine synthesis and glucose oxidation in rat corpus striatum
Insights
Propylthiouracil-induced thyroid deficiency in rats impairs acetylcholine synthesis in the corpus striatum. Developing cholinergic nerve terminals are reduced, but existing ones function normally.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- Thyroid hormones are crucial for normal brain development.
- Neonatal hypothyroidism can lead to long-term neurological deficits.
- Cholinergic system development is sensitive to thyroid status.
Purpose of the Study:
- To investigate the impact of propylthiouracil (PTU)-induced thyroid deficiency on acetylcholine synthesis and glucose metabolism in developing rat striatum.
- To assess the functional capacity of cholinergic nerve terminals in thyroid-deficient rats.
Main Methods:
- PTU administration to rats from postnatal day 2.
- In vitro measurement of [14C]acetylcholine synthesis from [14C]acetylcholine.
- Measurement of 14CO2 production from [U-14C]glucose in striatal prisms under varying potassium concentrations.
- Assessment of [3H]choline acetylation.
Main Results:
- PTU treatment significantly reduced [14C]acetylcholine synthesis (27-39%) in 3- and 6-week-old rats.
- Thyroid deficiency impaired glucose metabolism (14CO2 production) under high potassium conditions (31 mM K+).
- The acetylation of transported [3H]choline was unaffected by PTU-induced thyroid deficiency.
Conclusions:
- Neonatal thyroid deficiency leads to reduced development of cholinergic nerve terminals in the rat striatum.
- The intrinsic capacity of cholinergic terminals for potassium-stimulated neurotransmitter synthesis and choline acetylation appears preserved.
Abstract:
The effects of propylthiouracil (PTU)-induced thyroid deficiency on [14C]acetylcholine synthesis and 14CO2 production from [U-14C]glucose in vitro, by fine prisms of the corpus striatum were investigated in developing rats. Consistent with deficits in choline uptake and choline acetyltransferase activity (Kalaria et al.17), PTU-treatment from two days after birth significantly impaired (27-39%) [14C]acetylcholine synthesis in striatal tissue taken from 3- or 6-week-old animals. In the thyroid-deficient (Tx) animals, 14CO2 production from [14C]glucose was unchanged in incubations in the presence of 5 mM K+ but was significantly reduced (33%) in medium with 31 mM K+ concentration. The addition of 10 mM DL-3-hydroxybutyrate in incubations with 5 mM K+ persistently inhibited 14CO2 production by striatal samples from the Tx rats. The fraction acetylated of [3H]choline accumulated by striatal prisms was unaffected by the PTU-induced thyroid deficiency. These findings suggest the development of fewer cholinergic nerve terminals in striatum during neonatal thyroid deficiency. Cholinergic nerve terminals that develop seem unaffected in their capacity for K+-stimulation and in their ability to acetylate transported [3H]choline.