3,5-T2 and 3,3',5-T3 Regulate Cerebellar Thyroid Hormone Signalling and Myelin Molecular Dynamics in Tilapia.

In contrast to mammalian adults, myelination in teleosts occurs throughout their lifespan and most of the progenitor cells are originated in the cerebellum. To understand the role that thyroid hormones (THs) play in juvenile cerebellar myelination in teleosts, we identified and localised the expression of genes involved in TH signalling (mct8, oatp1c1, dio2, dio3, thraa and l-thrb1) and analysed the effects of the two bioactive THs, T2 and T3, upon their regulation, as well as upon some structural components of the myelination process. Ex vivo approaches using organotypic cerebellar cultures followed by FISH and qPCR showed gene-specific localisation and regulation of TH signalling genes in the cerebellar nuclei. In vivo approaches using methimazole (MMI)-treated juvenile tilapias replaced with low doses of T3 and T2 showed by immunofluorescence that myelin fibres in the cerebellum are more abundant in the granular layer and that their visible size is reduced after MMI treatment but partially restored with TH replacement, suggesting that low doses of TH promote the re-myelination process in an altered condition. Together, our data support the idea that T2 and T3 promote myelination via different pathways and prompt T2 as a target for further analysis as a promising therapy for hypomyelination.

Spinal LTP induced by sciatic nerve electrical stimulation enhances posterior triangular thalamic nociceptive responses.

Long-term potentiation (LTP) can be induced by electrical stimulation and gives rise to an increase in synaptic strength at the first relay. This phenomenon has been associated with learning and memory and also could be the origin of several pathological states elicited by an initial strong painful stimulus, such as some forms of neuropathic pain. We used high-frequency electrical stimulation of the sciatic nerve in anesthetized rats to produce spinal LTP. To evaluate the effect of spinal LTP on the activity of neurons in the posterior triangular nucleus of the thalamus (PoT), we applied an electrical stimulation (40 stimuli; 1ms; 0.5Hz; 1.5mA) to cutaneous tissues at 10-min intervals during at least 3h. In the majority of cases, PoT cells did not respond to cutaneous stimulation before LTP, but 50min after LTP induction PoT cells progressively began responding to the cutaneous stimulation. Furthermore, after 3h of LTP induction, PoT neurons could respond to cutaneous stimulation applied to different paws. Interestingly, the conduction velocities for the receptive field responses from the paw to the PoT cells were compatible with those of Aδ-fibers. Since PoT cells project to the insular cortex, the progressive increase in PoT activity and also the progressive unmasking of somatic receptive fields in response to LTP, place these cells in a key position to detect pain stimuli following central sensitization.