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Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

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Autor(es):
Lima-Silveira, Ludmila [1] ; Accorsi-Mendonca, Daniela [1] ; Bonagamba, Leni G. H. [1] ; Almado, Carlos Eduardo L. [1] ; da Silva, Melina P. [1] ; Nedoboy, Polina E. [2] ; Pilowsky, Paul M. [2] ; Machado, Benedito H. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Heart Res Inst, Sydney, NSW 2042 - Australia
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PHYSIOLOGY-LONDON; v. 597, n. 11, p. 2903-2923, JUN 2019.
Citações Web of Science: 0
Resumo

Key points Rats subjected to sustained hypoxia (SH) present increases in arterial pressure (AP) and in glutamatergic transmission in the nucleus tractus solitarius (NTS) neurons sending projections to ventrolateral medulla (VLM). Treatment with minocycline, a microglial inhibitor, attenuated the increase in AP in response to SH. The increase in the amplitude of glutamatergic postsynaptic currents in the NTS-VLM neurons, induced by postsynaptic mechanisms, was blunted by minocycline treatment. The number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS of minocycline-treated rats. The data show that microglial recruitment/proliferation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the observed increase in AP. Short-term sustained hypoxia (SH) produces significant autonomic and respiratory adjustments and triggers activation of microglia, the resident immune cells in the brain. SH also enhances glutamatergic neurotransmission in the NTS. Here we evaluated the role of microglial activation induced by SH on the cardiovascular changes and mainly on glutamatergic neurotransmission in NTS neurons sending projections to the ventrolateral medulla (NTS-VLM), using a microglia inhibitor (minocycline). Direct measurement of arterial pressure (AP) in freely moving rats showed that SH (24 h, fraction of inspired oxygen (FI,O2) 0.1) in vehicle and minocycline (30 mg/kg i.p. for 3 days)-treated groups produced a significant increase in AP in relation to control groups under normoxic conditions, but this increase was significantly lower in minocycline-treated rats. Whole-cell patch-clamp recordings revealed that the active properties of the membrane were comparable among the groups. Nevertheless, the amplitudes of glutamatergic postsynaptic currents, evoked by tractus solitarius stimulation, were increased in NTS-VLM neurons of SH rats. Changes in asynchronous glutamatergic currents indicated that the observed increase in amplitude was due to postsynaptic mechanisms. These changes were blunted in the SH group previously treated with minocycline. Using immunofluorescence, we found that the number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS neurons of minocycline-treated rats. Our data support the concept that microglial activation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the increase in AP observed in this experimental model. (AU)

Processo FAPESP: 13/06077-5 - Alterações nas redes neurais envolvidas na geração e controle das atividades simpática e respiratória em diferentes modelos experimentais de hipóxia
Beneficiário:Benedito Honorio Machado
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/11101-5 - A influência do processo inflamatório sobre a atividade dos neurônios do núcleo do trato solitário de ratos jovens submetidos à hipóxia mantida
Beneficiário:Ludmila Lima Silveira
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 17/13720-2 - Efeitos do tratamento com minociclina sobre a ativação microglial em ratos submetidos a hipóxia mantida
Beneficiário:Ludmila Lima Silveira
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto