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Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in L-Dopa-Induced Dyskinesia.
Gomez, G; Escande, M V; Suarez, L M; Rela, L; Belforte, J E; Moratalla, R; Murer, M G; Gershanik, O S; Taravini, I R E.
Afiliação
  • Gomez G; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
  • Escande MV; Instituto de Investigaciones Farmacológicas (ININFA), Laboratorio de Parkinson Experimental, CONICET - Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
  • Suarez LM; Instituto de Fisiología y Biofísica (IFIBIO) Bernardo Houssay, Grupo de Neurociencia de Sistemas, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
  • Rela L; Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • Belforte JE; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
  • Moratalla R; Instituto de Fisiología y Biofísica (IFIBIO) Bernardo Houssay, Grupo de Neurociencia de Sistemas, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
  • Murer MG; Instituto de Fisiología y Biofísica (IFIBIO) Bernardo Houssay, Grupo de Neurociencia de Sistemas, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
  • Gershanik OS; Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  • Taravini IRE; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
Mol Neurobiol ; 56(9): 6261-6275, 2019 Sep.
Article em En | MEDLINE | ID: mdl-30746639
Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts. Furthermore, we determined changes in PV-immunoreactive cell density by PV immunolabeling combined with Wisteria floribunda agglutinin (WFA) labeling to detect FSI in a PV-independent manner. We also explored the differential expression of striatal activity-regulated cytoskeleton-associated protein (Arc) and c-Fos in both types of MSNs as a measure of neuronal activation. Our results confirm previous findings of major structural changes in dendritic spine density after nigrostriatal denervation, which are further modified in the dyskinetic condition. Moreover, the finding of differential modifications in perisomatic GABAergic connectivity and neuronal activation in MSNs suggests an attempt by the system to regain homeostasis after denervation and an imbalance between excitation and inhibition leading to the development of dyskinesia after exposure to L-DOPA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Discinesias / Espinhas Dendríticas / Rede Nervosa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Discinesias / Espinhas Dendríticas / Rede Nervosa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos