Involvement of L-Triiodothyronine in Acetylcholine Metabolism in Adult Rat Cerebrocortical Synaptosomes

Abstract

Despite the recently emerging notion of thyroid-hormone involvement in neurotransmission in the adult mammalian brain, adequate evidence for a cellular basis of the process is still lacking. The present study indicates the involvement of thyroid hormones in cholinergic system of the adult rat cerebral cortex. Administration of L-triiodothyronine (T3, 0.025 to 4 microg/g) in single doses increased the synaptosomal acetylcholinesterase (AchE) and Mg2+-ATPase activity maximally at 24 hours in a dose-dependent way. Propylthiouracil (PTU)-treated hypothyroid rats showed a significant increase in AchE and Mg2+-ATPase activity compared to euthyroid rats. T3-treatment on hypothyroid rats decreased AchE activity in synaptosomes compared to the hypothyroid synaptosomal values. Mg2+-ATPase activity found in (PTU + T3)-treated group and T3-treated group remained high. These results predict that T3 stimulates acetylcholine (Ach) metabolism by increasing AchE activity as well as uptake of the released Ach through an increase in synaptosomal Mg2+-ATPase activity. This indicates a positive impact of T3 on the cholinergic system in the adult mammalian brain.

Maintenance of brain thyroid hormone level during peripheral hypothyroid condition in adult rat

“…3). The high local synaptosomal level of T3 might have caused a depression in the AChE activity, exerting a feedback inhibition or toxic-inhibitory effect (Sarkar and Ray, 2001). Moreover, there are evidences to correlate the inhibition of synaptosomal Na + -K + -ATPase activity with the release of ACh and enhanced activity of AChE and vice versa (Meyer and Cooper, 1981).…”

“…Synaptosomal acetylcholinesterase (AChE, EC 3.1.1.7) activity was estimated according to the method of Ellman et al (1961), with slight modifications (Sarkar and Ray, 2001). Briefly, the synaptosomal suspension was incubated in a medium containing 60 mM Tris-HCl buffer (pH 7.4) and 5 mM acetyl-thiocholine iodide for 30 min at 37°C.…”

Cerebral Accumulation of TC-99M Ethyl Cysteinate Dimer (ECD) in Severe, Transient Hypothyroidism

“…Cell culture studies have shown that the amount of cell membrane-bound esterase activity is inversely proportional to Tc-99m ECD uptake (Walovitch et al, 1994). Thyroid axis hormonal changes have been demonstrated in animal studies to modulate esterase production and activity in both a positive and a negative manner, depending in part on the particular type of esterase and the biochemical milieu (Goswami and Rosenberg, 1985;Banerjee and Ray, 2002;Takahashi et al, 2001;Sarkar and Ray, 2001). Given the aberrations in acid-base balance and electrolyte metabolism known to occur during hypothyroidism (Moses and Scheinman, 1996), the probable resultant pH changes, and the pH-related ionization and trapping of ligands with the same N 2 S 2 structure as ECD (Verbruggen, 1998), it is plausible that a pH change in the biochemical brain milieu, with secondary effects on esterase production and function, may contribute to local changes in Tc-99m ECD retention during hypothyroidism.…”

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats

“…Besides the critical role of thyroid hormones (THs) in brain development and metabolism, recent investigations have highlighted the involvement of these hormones in the adult mammalian brain neurotransmission [1][2][3][4]. In particular, a very close association exists between the THs and brain cholinergic function [5].…”