Thyroid hormone deiodinases response in brain of spontaneausly hypertensive rats after hypotensive effects induced by mandibular extension

Abstract

Purpose:The deiodinases activate or inactivate the thyroid hormones (TH) in virtually all tissues in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2 and DIO3, have different catalytic functions and regulate TH tissue distribution. The aim of the present study was to evaluate the modulation of gene expression of the deiodinases and TH transporters and protein levels of DIO1 in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two successive mandibular extension (ME).Methods ME was performed on anesthetized rats by a dilatator appropriately designed and Real Time PCR and Western Blotting techniques were employed for gene expression and protein level study.Results mean blood pressure (MBP) significantly decreased in 2ME-treated rats when compared to sham-operated rats (p<0.001) and this decrease lasted for the entire observation period. In gene expression analysis, in 2ME-treated rats we did not observe any significant variation of DIO1 and DIO3 with respect to the sham-operated rats. Differently, DIO2 gene expression significantly increased in frontal area of 2ME-treated rats, with respect to sham-operated rats (p<0.01).Furthermore, in parietal area, protein levels of DIO1 in 2ME-treated rats were significantly higher than in sham-operated rats (p<0.01). Moreover MCT8 and OATP1C1 both resulted significantly higher (p<0.05 and p<0.001) in sham frontal cortex. ConclusionIn summary, our data on SHRs, while confirming the hypotensive effect of two MEs, show that the treatment also solicits the three deiodinases production in the cerebral cortex.

The Physiological Functions and Polymorphisms of Type II Deiodinase

“…In mice that experienced 3 hours of status epilepticus (SE) caused by pilocarpine, the mRNA expression of Dio2 increased rapidly in the hippocampus, amygdala, and prefrontal cortex; however, the targeted disruption of Dio2 in astrocytes of mice had effects on highly induced genes in the hippocampus associated with inflammation, apoptosis, and cell death, suggesting that Dio2 induction caused by SE accelerated the production of T3 in different areas of the CNS and modified the hippocampal gene expression profile, affecting the balance between adaptive and maladaptive mechanisms [ 64 ]. Moreover, Dio2 mRNA expression significantly increased in the frontal cortex of two mandibular extension-treated rats compared with sham-operated rats, indicating the major involvement of Dio2 in an attempt to restore more physiological conditions and correct T3 levels, associated with normotensive status in the brain [ 65 ]. A recent result also showed that mice lacking both monocarboxylate transporter 8 ( Mct8 ) and Dio2 presented peripheral and brain hypothyroidism; the severity of the brain hypothyroidism seemed permanent and varied across regions, with the striatum being a particularly affected area, and brain alterations were observed at the histological level compatible with TH deficiency and impaired motor skills [ 66 ].…”

Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions

“…3 ). Moreover, the same study showed higher DIO1 protein levels in the parietal (but not frontal) cortex of SHR brain after two mandibular extensions, raising interesting questions about the role of this enzyme in TH system homeostasis in hypertensive conditions, which await further investigations [ 56 ].…”