Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/259170
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | GABAergic deficits in absence of LPA1 receptor, associated anxiety-like and coping behaviors, and amelioration by interneuron precursor transplants into the dorsal hippocampus |
Autor: | Rosell-Valle, Cristina; Martínez-Losa, Magdalena CSIC ORCID; Matas-Rico, Elisa; Castilla Ortega, Estela; Zambrana-Infantes, Emma; Gómez-Conde, Ana Isabel; Sánchez-Salido, Lourdes; Ladrón de Guevara-Miranda, David; Pedraza, Carmen; Serrano-Castro, Pedro Jesús; Chun, Jerold; Rodríguez de Fonseca, Fernando; Álvarez-Dolado, Manuel CSIC ORCID CVN; Santín, Luis J.; Estivill-Torrús, Guillermo | Palabras clave: | Lysophosphatidic acid receptor 1 GABA Interneurons Cell-based therapy maLPA1-null mice |
Fecha de publicación: | 1-abr-2021 | Editor: | Springer Nature | Citación: | Brain Structure and Function 226: 1479-1495 (2021) | Resumen: | Defects in GABAergic function can cause anxiety- and depression-like behaviors among other neuropsychiatric disorders. Therapeutic strategies using the transplantation of GABAergic interneuron progenitors derived from the medial ganglionic eminence (MGE) into the adult hippocampus reversed the symptomatology in multiple rodent models of interneuron-related pathologies. In turn, the lysophosphatidic acid receptor LPA has been reported to be essential for hippocampal function. Converging evidence suggests that deficits in LPA receptor signaling represent a core feature underlying comparable hippocampal dysfunction and behaviors manifested in common neuropsychiatric conditions. Here, we first analyzed the GABAergic interneurons in the hippocampus of wild-type and maLPA-null mice, lacking the LPA receptor. Our data revealed a reduction in the number of neurons expressing GABA, calcium-binding proteins, and neuropeptides such as somatostatin and neuropeptide Y in the hippocampus of maLPA-null mice. Then, we used interneuron precursor transplants to test links between hippocampal GABAergic interneuron deficit, cell-based therapy, and LPA receptor-dependent psychiatric disease-like phenotypes. For this purpose, we transplanted MGE-derived interneuron precursors into the adult hippocampus of maLPA-null mice, to test their effects on GABAergic deficit and behavioral symptoms associated with the absence of the LPA receptor. Transplant studies in maLPA-null mice showed that grafted cells were able to restore the hippocampal host environment, decrease the anxiety-like behaviors and neutralize passive coping, with no abnormal effects on motor activity. Furthermore, grafted MGE-derived cells maintained their normal differentiation program. These findings reinforce the use of cell-based strategies for brain disorders and suggest that the LPA receptor represents a potential target for interneuron-related neuropsychiatric disorders. | Versión del editor: | http://dx.doi.org/10.1007/s00429-021-02261-4 | URI: | http://hdl.handle.net/10261/259170 | DOI: | 10.1007/s00429-021-02261-4 | Identificadores: | doi: 10.1007/s00429-021-02261-4 e-issn: 1863-2661 issn: 1863-2653 |
Aparece en las colecciones: | (CABIMER) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
4
checked on 22-abr-2024
WEB OF SCIENCETM
Citations
3
checked on 20-feb-2024
Page view(s)
26
checked on 29-abr-2024
Download(s)
5
checked on 29-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.