Articles producció científica> Bioquímica i Biotecnologia

Peroxisomal Proliferator-Activated Receptor β/δ Deficiency Induces Cognitive Alterations

  • Identification data

    Identifier: imarina:9280249
    Authors:
    Espinosa-Jiménez TBusquets OCano ASánchez-López EVerdaguer EParcerisas AOlloquequi JAuladell CFolch JWahli WVázquez-Carrera MCamins AEttcheto M
    Abstract:
    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), the most PPAR abundant isotype in the central nervous system, is involved in microglial homeostasis and metabolism, whose disturbances have been demonstrated to play a key role in memory impairment. Although PPARβ/δ function is well-established in metabolism, its contribution to neuronal and specifically memory process is underexplored. Therefore, the aim of the study is to determine the role of PPARβ/δ in the neuropathological pathways involved in memory impairment and as to whether a risk factor implicated in memory loss such as obesity modulates neuropathological markers. To carry out this study, 6-month-old total knock-out for the Ppard gene male mice with C57BL/6X129/SV background (PPARβ/δ-/-) and wild-type (WT) littermates with the same genetic background were used. Animals were fed, after the weaning (at 21 days old), and throughout their growth, either conventional chow (CT) or a palmitic acid-enriched diet (HFD). Thus, four groups were defined: WT CT, WT HFD, PPARβ/δ-/- CT, and PPARβ/δ-/- HFD. Before sacrifice, novel object recognition test (NORT) and glucose and insulin tolerance tests were performed. After that, animals were sacrificed by intracardiac perfusion or cervical dislocation. Different techniques, such as GolgiStain kit or immunofluorescence, were used to evaluate the role of PPARβ/δ in memory dysfunction. Our results showed a decrease in dendritic spine density and synaptic markers in PPARβ/δ-/- mice, which were corroborated in the NORT. Likewise, our study demonstrated that the lack of PPARβ/δ receptor enhances gliosis in the hippocampus, contributing to astrocyte and microglial activation and to the increase in neuroinflammatory biomarkers. Additionally, alterations in the hippocampal insu
  • Others:

    Author, as appears in the article.: Espinosa-Jiménez T; Busquets O; Cano A; Sánchez-López E; Verdaguer E; Parcerisas A; Olloquequi J; Auladell C; Folch J; Wahli W; Vázquez-Carrera M; Camins A; Ettcheto M
    Department: Bioquímica i Biotecnologia
    URV's Author/s: Folch Lopez, Jaume
    Keywords: T2dm Synapsis Pparβ/δ Neuroinflammation Memory impairment Insulin signaling High-fat diet Dendritic spines
    Abstract: Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), the most PPAR abundant isotype in the central nervous system, is involved in microglial homeostasis and metabolism, whose disturbances have been demonstrated to play a key role in memory impairment. Although PPARβ/δ function is well-established in metabolism, its contribution to neuronal and specifically memory process is underexplored. Therefore, the aim of the study is to determine the role of PPARβ/δ in the neuropathological pathways involved in memory impairment and as to whether a risk factor implicated in memory loss such as obesity modulates neuropathological markers. To carry out this study, 6-month-old total knock-out for the Ppard gene male mice with C57BL/6X129/SV background (PPARβ/δ-/-) and wild-type (WT) littermates with the same genetic background were used. Animals were fed, after the weaning (at 21 days old), and throughout their growth, either conventional chow (CT) or a palmitic acid-enriched diet (HFD). Thus, four groups were defined: WT CT, WT HFD, PPARβ/δ-/- CT, and PPARβ/δ-/- HFD. Before sacrifice, novel object recognition test (NORT) and glucose and insulin tolerance tests were performed. After that, animals were sacrificed by intracardiac perfusion or cervical dislocation. Different techniques, such as GolgiStain kit or immunofluorescence, were used to evaluate the role of PPARβ/δ in memory dysfunction. Our results showed a decrease in dendritic spine density and synaptic markers in PPARβ/δ-/- mice, which were corroborated in the NORT. Likewise, our study demonstrated that the lack of PPARβ/δ receptor enhances gliosis in the hippocampus, contributing to astrocyte and microglial activation and to the increase in neuroinflammatory biomarkers. Additionally, alterations in the hippocampal insulin receptor pathway were found. Interestingly, while some of the disturbances caused by the lack of PPARβ/δ were not affected by feeding the HFD, others were exacerbated or required the combination of both factors. Taken together, the loss of PPARβ/δ-/- affects neuronal and synaptic structure, contributing to memory dysfunction, and they also present this receptor as a possible new target for the treatment of memory impairment.
    Thematic Areas: Psicología Pharmacology (medical) Pharmacology & pharmacy Pharmacology Odontología Medicina veterinaria Medicina ii Medicina i Interdisciplinar Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: jaume.folch@urv.cat
    Author identifier: 0000-0002-5051-8858
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.frontiersin.org/articles/10.3389/fphar.2022.902047/full
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Frontiers In Pharmacology. 13
    APA: Espinosa-Jiménez T; Busquets O; Cano A; Sánchez-López E; Verdaguer E; Parcerisas A; Olloquequi J; Auladell C; Folch J; Wahli W; Vázquez-Carrera M; Cam (2022). Peroxisomal Proliferator-Activated Receptor β/δ Deficiency Induces Cognitive Alterations. Frontiers In Pharmacology, 13(), -. DOI: 10.3389/fphar.2022.902047
    Article's DOI: 10.3389/fphar.2022.902047
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2022
    Publication Type: Journal Publications
  • Keywords:

    Pharmacology,Pharmacology & Pharmacy,Pharmacology (Medical)
    T2dm
    Synapsis
    Pparβ/δ
    Neuroinflammation
    Memory impairment
    Insulin signaling
    High-fat diet
    Dendritic spines
    Psicología
    Pharmacology (medical)
    Pharmacology & pharmacy
    Pharmacology
    Odontología
    Medicina veterinaria
    Medicina ii
    Medicina i
    Interdisciplinar
    Farmacia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Biodiversidade
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