Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether end...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/6/610 |
| _version_ | 1827691364565909504 |
|---|---|
| author | Jessica C. Gaspar Catherine Healy Mehnaz I. Ferdousi Michelle Roche David P. Finn |
| author_facet | Jessica C. Gaspar Catherine Healy Mehnaz I. Ferdousi Michelle Roche David P. Finn |
| author_sort | Jessica C. Gaspar |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPARα antagonist), GSK0660 (PPARβ/δ antagonist), GW9662 (PPARγ antagonist), and <i>N</i>-palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund’s Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPARα further impaired spatial memory in CFA-treated rats. <i>N</i>-oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPARα signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection. |
| first_indexed | 2024-03-10T10:58:49Z |
| format | Article |
| id | doaj.art-aaaf85c6dd284c9ea4fbaa73163adbd1 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T10:58:49Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-aaaf85c6dd284c9ea4fbaa73163adbd12023-11-21T21:39:51ZengMDPI AGBiomedicines2227-90592021-05-019661010.3390/biomedicines9060610Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in RatsJessica C. Gaspar0Catherine Healy1Mehnaz I. Ferdousi2Michelle Roche3David P. Finn4Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, IrelandPharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, IrelandPharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, IrelandGalway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, IrelandPharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, IrelandPeroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPARα antagonist), GSK0660 (PPARβ/δ antagonist), GW9662 (PPARγ antagonist), and <i>N</i>-palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund’s Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPARα further impaired spatial memory in CFA-treated rats. <i>N</i>-oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPARα signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection.https://www.mdpi.com/2227-9059/9/6/610peroxisome-proliferator activated receptorcognitionanxietyspatial memorycomplete Freund adjuvantPEA |
| spellingShingle | Jessica C. Gaspar Catherine Healy Mehnaz I. Ferdousi Michelle Roche David P. Finn Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats Biomedicines peroxisome-proliferator activated receptor cognition anxiety spatial memory complete Freund adjuvant PEA |
| title | Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats |
| title_full | Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats |
| title_fullStr | Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats |
| title_full_unstemmed | Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats |
| title_short | Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats |
| title_sort | pharmacological blockade of pparα exacerbates inflammatory pain related impairment of spatial memory in rats |
| topic | peroxisome-proliferator activated receptor cognition anxiety spatial memory complete Freund adjuvant PEA |
| url | https://www.mdpi.com/2227-9059/9/6/610 |
| work_keys_str_mv | AT jessicacgaspar pharmacologicalblockadeofpparaexacerbatesinflammatorypainrelatedimpairmentofspatialmemoryinrats AT catherinehealy pharmacologicalblockadeofpparaexacerbatesinflammatorypainrelatedimpairmentofspatialmemoryinrats AT mehnaziferdousi pharmacologicalblockadeofpparaexacerbatesinflammatorypainrelatedimpairmentofspatialmemoryinrats AT michelleroche pharmacologicalblockadeofpparaexacerbatesinflammatorypainrelatedimpairmentofspatialmemoryinrats AT davidpfinn pharmacologicalblockadeofpparaexacerbatesinflammatorypainrelatedimpairmentofspatialmemoryinrats |