Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice

Background: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found...

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Autores: García Cerro, Susana; Rueda Revilla, Noemí|||0000-0001-9583-3336; Vidal Sánchez, Verónica; Puente Bedia, Alba; Campa Fernández, Víctor Manuel; Lantigua Romero, Sara; Narcís Majos, Josep Oriol; Velasco, Ana; Bartesaghi, Renata; Martínez-Cué, Carmen|||0000-0002-2137-1156
Tipo de documento: Artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Lenguaje:Inglés
OAI Identifier:oai:repositorio.unican.es:10902/21334
Acceso en línea:http://hdl.handle.net/10902/21334
Nivel de acceso:Acceso abierto
Palabra clave:Down Syndrome
Ts65Dn Mice
Cognition
Linolenic Acid
Neurogenesis
Oleic Acid
Prenatal Treatment
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author García Cerro, Susana
author2 Rueda Revilla, Noemí|||0000-0001-9583-3336
Vidal Sánchez, Verónica
Puente Bedia, Alba
Campa Fernández, Víctor Manuel
Lantigua Romero, Sara
Narcís Majos, Josep Oriol
Velasco, Ana
Bartesaghi, Renata
Martínez-Cué, Carmen|||0000-0002-2137-1156
author2_role author
author
author
author
author
author
author
author
author
author_browse Bartesaghi, Renata
Campa Fernández, Víctor Manuel
García Cerro, Susana
Lantigua Romero, Sara
Martínez-Cué, Carmen|||0000-0002-2137-1156
Narcís Majos, Josep Oriol
Puente Bedia, Alba
Rueda Revilla, Noemí|||0000-0001-9583-3336
Velasco, Ana
Vidal Sánchez, Verónica
author_facet García Cerro, Susana
Rueda Revilla, Noemí|||0000-0001-9583-3336
Vidal Sánchez, Verónica
Puente Bedia, Alba
Campa Fernández, Víctor Manuel
Lantigua Romero, Sara
Narcís Majos, Josep Oriol
Velasco, Ana
Bartesaghi, Renata
Martínez-Cué, Carmen|||0000-0002-2137-1156
author_role author
collection UCrea Repositorio Abierto de la Universidad de Cantabria
description Background: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages. Objectives: As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid. Methods: In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs. Results: Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals. Conclusion: The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits.
eu_rights_str_mv openAccess
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institution Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
language eng
network_acronym_str ES
network_name_str España
oai_identifier_str oai:repositorio.unican.es:10902/21334
publishDate 2020
publishDateSort 2020
publisher Oxford University Press
publisherStr Oxford University Press
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
spelling Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice García Cerro, Susana Rueda Revilla, Noemí|||0000-0001-9583-3336 Vidal Sánchez, Verónica Puente Bedia, Alba Campa Fernández, Víctor Manuel Lantigua Romero, Sara Narcís Majos, Josep Oriol Velasco, Ana Bartesaghi, Renata Martínez-Cué, Carmen|||0000-0002-2137-1156 Down Syndrome Ts65Dn Mice Cognition Linolenic Acid Neurogenesis Oleic Acid Prenatal Treatment Background: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages. Objectives: As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid. Methods: In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs. Results: Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals. Conclusion: The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits. This study was supported by “Fondazione Generali e Assicurazioni Generali”, Italy; Fundación Tatiana Pérez de Guzmán el Bueno, IDIVAL (NVAL 19/23), and the Spanish Ministry of Economy and Competitiveness (PSI-2016- 76194-R, AEI/FEDER, EU). Oxford University Press http://hdl.handle.net/10902/21334
spellingShingle Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
García Cerro, Susana
Down Syndrome
Ts65Dn Mice
Cognition
Linolenic Acid
Neurogenesis
Oleic Acid
Prenatal Treatment
title Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
title_full Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
title_fullStr Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
title_full_unstemmed Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
title_short Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
title_sort Prenatal Administration of Oleic Acid or Linolenic Acid Reduces Neuromorphological and Cognitive Alterations in Ts65dn Down Syndrome Mice
topic Down Syndrome
Ts65Dn Mice
Cognition
Linolenic Acid
Neurogenesis
Oleic Acid
Prenatal Treatment
topic_facet Down Syndrome
Ts65Dn Mice
Cognition
Linolenic Acid
Neurogenesis
Oleic Acid
Prenatal Treatment
url http://hdl.handle.net/10902/21334