Aims: Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1–Plin5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. Methods: We performed real-time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. Results: Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, whereas Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with early tauopathy or Alzheimer's disease and is associated with IL-6 expression. Conclusions: Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration.
Expression pattern of perilipins in human brain during aging and in Alzheimer's disease / Conte M.; Medici V.; Malagoli D.; Chiariello A.; Cirrincione A.; Davin A.; Chikhladze M.; Vasuri F.; Legname G.; Ferrer I.; Vanni S.; Marcon G.; Poloni T.E.; Guaita A.; Franceschi C.; Salvioli S.. - In: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY. - ISSN 0305-1846. - STAMPA. - 48:(2022), pp. e12756.1-e12756.14. [10.1111/nan.12756]
Expression pattern of perilipins in human brain during aging and in Alzheimer's disease
Conte M.;Chiariello A.;Vasuri F.;Franceschi C.;Salvioli S.
2022
Abstract
Aims: Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1–Plin5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. Methods: We performed real-time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. Results: Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, whereas Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with early tauopathy or Alzheimer's disease and is associated with IL-6 expression. Conclusions: Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration.| File | Dimensione | Formato | |
|---|---|---|---|
|
Conte et al., NAN 2022.pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
29.64 MB
Formato
Adobe PDF
|
29.64 MB | Adobe PDF | Visualizza/Apri |
|
nan12756-sup-0001-figure_s1.tif
accesso aperto
Descrizione: Figure S1. Immunohistochemical analysis for Plin1 and Plin4. Plin1 (A-D) and Plin4 (E-H) in autoptic samples from human cerebellum (A, E), temporal cerebral cortex (B, F), frontal cerebral cortex (C, C’, G, G’) and hippocampus (D, H). The staining results largely negative, with only a very weak expression in the cytoplasm of a few neurons of the cortical grey matter (C’-G’). Scale bars: 460 μm (A-H); 55 μm (C’, G’).
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
24.68 MB
Formato
TIFF
|
24.68 MB | TIFF | Visualizza/Apri |
|
nan12756-sup-0002-figure_s2.tif
accesso aperto
Descrizione: Figure S2. Fluorescence microscopy analysis of Plin2 and Plin3 in neurons and astrocytes. Data were derived from frontal cortex samples of one old subject and one AD patient. (A-C) Plin2 (red fluorescence) colocalization with NeuN (green fluorescence). Scale bar: 10.54 μm. (D) Morphometric analysis of Plin2 staining on 343 NeuN+ cells (neurons). (E-G) Plin3 (red fluorescence) colocalization with GFAP (green fluorescence). Scale bar: 6 μm. (H) Morphometric analysis of Plin3 staining on 155 GFAP+ cells (astrocytes).
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
24.68 MB
Formato
TIFF
|
24.68 MB | TIFF | Visualizza/Apri |
|
nan12756-sup-0003-figure_s3.tif
accesso aperto
Descrizione: Figure S3. Confocal microscopy analysis of Plin3 and Plin5 in oligodendrocytes. Representative examples showing cells positive for the oligodendrocyte marker Olig2 that are also positive for Plin5 but not Plin3. (A-C) Olig2 (green fluorescence) (A), Plin3 (red fluorescence) (B), and merge (C). (D-F) Olig2 (green fluorescence) (D), Plin5 (red fluorescence) (E), and merge (F). Scale bars: 5 μm.
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
14.75 MB
Formato
TIFF
|
14.75 MB | TIFF | Visualizza/Apri |
|
nan12756-sup-0004-figure_s4.tif
accesso aperto
Descrizione: Figure S4. WB analysis of Plins protein in frontal cortex from adult, old subjects and centenarians (CENT). (A) Representative immunoblotting image of Plin2, Plin3, Plin5 in frontal cortex. (B-D) Relative protein expression of Plin2 (B), Plin3 (C) and Plin5 (D). The bars represent mean ± SE. Kruskal-Wallis and Bonferroni tests were applied. WB quantification of Plins expression was performed using ImageJ software and normalised to GAPDH protein expression.
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
24.69 MB
Formato
TIFF
|
24.69 MB | TIFF | Visualizza/Apri |
|
nan12756-sup-0005-figure_s5.tif
accesso aperto
Descrizione: Figure S5. Immunohistochemistry analysis of Plin2 in two Early Tauopathy patients (ET1 and ET2). (A-H) In ET1 high immunoreactivity for Plin2 is homogeneously distributed in apical dendrites and in some neurons of frontal cortex (A-D), Plin2 is well expressed also in hippocampus (F) both in cornu ammonis (G) and dentate gyrus (H). pTAU (AT8 antibody) is clearly evident in the CA1 and subiculum areas (E). (I-O) In ET2 a Plin2 staining similar to ET1 was observed both in frontal cortex (I-L) and hippocampus (N-O); in CA1 immunopositivity for AT8 is shown (M).
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
24.68 MB
Formato
TIFF
|
24.68 MB | TIFF | Visualizza/Apri |
|
NAN-48-0-s005.docx
accesso aperto
Descrizione: Table S1. Information on human brain samples divided according to the brain banks of origin. Table S2. List of primary antibodies used.
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC)
Dimensione
32.7 kB
Formato
Microsoft Word XML
|
32.7 kB | Microsoft Word XML | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
