Thyrotropin releasing hormone (TRH) and its analog, RGH-2202, accelerate maturation of cerebellar neurons in vitro

Giacomo Casabona, Valeria Bruno, Maria Vincenza Catania, Maria Angela Sortino, Ferdinando Nicoletti, Umberto Scapagnini, Pier Luigi Canonico

Research output: Contribution to journalArticlepeer-review

Abstract

We have studied the "trophic" action of thyrotropin releasing hormone (TRH) in cultured cerebellar granule cells, a pure and homogenous population of glutamatergic neurons. As an index of neuronal maturation, we have measured the uptake of d-[3H]aspartate (a non-metabolizable analog of glutamate) at different days of maturation in vitro (DIV). In control cultures, d-[3H]Aspartate increased linealy during maturation reaching plateau values between 7 and 9 DIV; daily addition of TRH tartrate (TRH-t) or RGH-2202 (a TRH analog) accelerated in a concentration-dependent manner the maturation profile of d-[3H]aspartate uptake. This effect was more pronounced for RGH-2202; in cultures treated daily with RGH-2202, d-[3H]aspartate uptake was fully expressed after 3 DIV. Neither TRH-t nor RGH-2202 significantly increased d-[3H]aspartate uptake in mature cells, excluding a direct action on the glutamate transport system. Both compounds specifically potentiated the increase in [3H]inositol monophosphate formation (but not the stimulation of 45Ca2+ influx) induced by N-methyl-d-aspartate (NMDA) receptor agonists, without affecting the stimulation of inositol phospholipid hydrolysis by quisqualate or carbamylcholine. We suggest that, in cultured cerebellar granule cells, TRH and RGH-2202 enhance the trophic action of endogenous glutamate by amplifying some of the intracellular events that follow the influx of extracellular Ca2+ through NMDA-gated ion channels.

Original languageEnglish
Pages (from-to)179-183
Number of pages5
JournalDevelopmental Brain Research
Volume69
Issue number2
DOIs
Publication statusPublished - Oct 23 1992

Keywords

  • Cerebellar neuron
  • Excitatory amino acid
  • Maturation
  • RGH-2202
  • Thyrotropin-releasing hormone

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

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