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1000 Titel
  • Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis
1000 Autor/in
  1. Nidadavolu, Prakash |
  2. Bilkei-Gorzo, Andras |
  3. Effah, Felix |
  4. Leidmaa, Este |
  5. Schürmann, Britta |
  6. Berger, Moritz |
  7. Bindila, Laura |
  8. Schmid, Matthias |
  9. Lutz, Beat |
  10. Zimmer, Andreas |
  11. Bailey, Alexis |
1000 Erscheinungsjahr 2022
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-09-06
1000 Erschienen in
1000 Quellenangabe
  • 23(18):10254
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/ijms231810254 |
1000 Ergänzendes Material
  • https://www.mdpi.com/1422-0067/23/18/10254#app1-ijms-23-10254 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1. In the present study, we detailed the changes in the eCB system during the aging process using different complementary techniques in mouse brains of five different age groups, ranging from adolescence to old age. Our findings indicate that the eCB system is most strongly affected in middle-aged mice (between 9 and 12 months of age) in a brain region-specific manner. We show that 2-arachidonoylglycerol (2-AG) was prominently decreased in the Hip and moderately in caudate putamen (CPu), whereas anandamide (AEA) was decreased in both CPu and medial prefrontal cortex along with cingulate cortex (mPFC+Cg), starting from 6 months until 12 months. Consistent with the changes in 2-AG, the 2-AG synthesizing enzyme diacylglycerol lipase α (DAGLα) was also prominently decreased across the sub-regions of the Hip. Interestingly, we found a transient increase in CB1 immunoreactivity across the sub-regions of the Hip at 9 months, a plausible compensation for reduced 2-AG, which ultimately decreased strongly at 12 months. Furthermore, quantitative autoradiography of CB1 revealed that [3H]CP55940 binding markedly increased in the Hip at 9 months. However, unlike the protein levels, CB1 binding density did not drop strongly at 12 months and at old age. Furthermore, [3H]CP55940 binding was significantly increased in the lateral entorhinal cortex (LEnt), starting from the middle age until the old age. Altogether, our findings clearly indicate a middle-age crisis in the eCB system, which could be a potential time window for therapeutic interventions to abrogate the course of cognitive aging.
1000 Sacherschließung
lokal cognitive functions
lokal endocannabinoid system
lokal aging
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/TmlkYWRhdm9sdSwgUHJha2FzaA==|https://frl.publisso.de/adhoc/uri/Qmlsa2VpLUdvcnpvLCBBbmRyYXM=|https://orcid.org/0000-0001-5623-914X|https://frl.publisso.de/adhoc/uri/TGVpZG1hYSwgRXN0ZQ==|https://frl.publisso.de/adhoc/uri/U2Now7xybWFubiwgQnJpdHRh|https://frl.publisso.de/adhoc/uri/QmVyZ2VyLCBNb3JpdHo=|https://orcid.org/0000-0001-5538-2008|https://frl.publisso.de/adhoc/uri/U2NobWlkLCBNYXR0aGlhcw==|https://frl.publisso.de/adhoc/uri/THV0eiwgQmVhdA==|https://frl.publisso.de/adhoc/uri/WmltbWVyLCBBbmRyZWFz|https://orcid.org/0000-0003-1541-1964
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Germany’s Excellence Strategy |
1000 Fördernummer
  1. 426320013; 461228630; 324087152
  2. 390873048
1000 Förderprogramm
  1. -
  2. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer 426320013; 461228630; 324087152
  2. 1000 joinedFunding-child
    1000 Förderer Germany’s Excellence Strategy |
    1000 Förderprogramm -
    1000 Fördernummer 390873048
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6440445.rdf
1000 Erstellt am 2023-02-27T08:20:43.315+0100
1000 Erstellt von 317
1000 beschreibt frl:6440445
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Mon Feb 27 08:21:42 CET 2023
1000 Objekt bearb. Mon Feb 27 08:21:29 CET 2023
1000 Vgl. frl:6440445
1000 Oai Id
  1. oai:frl.publisso.de:frl:6440445 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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