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Artículo

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in l-Dopa-Induced Dyskinesia

Gomez, GimenaIcon ; Escande, Mariela VeronicaIcon ; Suarez, L.M.; Rela, LorenaIcon ; Belforte, Juan EmilioIcon ; Moratalla, R.; Murer, Mario GustavoIcon ; Gershanik, Oscar Samuel; Taravini, Irene Rita EloisaIcon
Fecha de publicación: 01/2019
Editorial: Humana Press
Revista: Molecular Neurobiology
ISSN: 0893-7648
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias

Resumen

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.
Palabras clave: DENDRITIC SPINES , L-DOPA-INDUCED DYSKINESIA , MEDIUM SPINY NEURON , PARKINSON’S DISEASE , PARVALBUMIN
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/127628
URL: https://link.springer.com/article/10.1007%2Fs12035-019-1515-4
DOI: https://doi.org/10.1007/s12035-019-1515-4
Colecciones
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Gomez, Gimena; Escande, Mariela Veronica; Suarez, L.M.; Rela, Lorena; Belforte, Juan Emilio; et al.; Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in l-Dopa-Induced Dyskinesia; Humana Press; Molecular Neurobiology; 56; 9; 1-2019; 6261-6275
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