de ceglia Marialuisa

PhD Graduate

PhD program:: XXXIII



Thesis title: The endocannabinoid system as possible target for the treatment of obesity related disorders: beyond cannabinoid receptors

Worldwide, obesity is one of the most diffused pathologies. Several lines of recent evidence link obesity with a higher risk of neurological pathologies such as anxiety and depression; this consideration stems from the observation that palatable food consumption becomes sometimes necessary to overcome negative mental states, thus sustaining the vicious circle of “food addiction”. Endogenous acylethanolamides (such as anandamide, oleoylethanolamide, palmitoylethanolamide) might play a key role in this scenario since they participate to the mechanisms regulating both reward and mood tone. The present study aims to explore whether the abstinence from a palatable diet, after a long-term ad libitum consumption of it, might produce alterations of the emotional reactivity and mood tone and whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by PF-3845 treatment (which causes an increase of acylethanolamide tone) might ameliorate such alterations. We used a rat model of diet-induced obesity based on a cafeteria-style diet. After the first 40 days of extended exposure to cafeteria diet, rats underwent an abstinence period of 28 days. During this period, animals were separated in two different groups: one group was chronically treated with PF-3845 (10 mg/kg, intraperitoneally) and the other group was treated with vehicle (ethanol/tween80/saline 5/5/90). At the end of the treatment rats were subjected to behavioral tests such as the open field test, the elevated plus maze and the forced swimming test and then were sacrificed. Brains were collected to investigate markers of monoaminergic transmission, endocannabinoid tone and inflammation in different brain areas implicated in reward, anxiety and depression. To meet this aim we used different experimental approaches including immunofluorescence, HPLC and western blot analysis. Pearson correlations tests were also conducted to correlate behavioural parameters to monoamine tissue levels in the different brain areas, as well as to investigate monoaminergic and endocannabinoid protein correlations throughout the different brain areas analysed. Our results demonstrate that long term abstinence from a palatable diet might impact both mood and reward processes: in particular, animals subjected to cafeteria diet withdrawal show an anxiety-like behavior and a depressive-like phenotype. Moreover, several neurochemical alterations are also detected in key brain areas involved in the control of mood and reward processes. These include alterations of the expression of proteins partaking to the endocannabinoid system and to the inflammatory-response, alterations in the monoaminergic tone. The repeated administration of the FAAH inhibitor PF-3845 during the abstinence period exerts an anxiolytic and antidepressant effect in abstinent rats and is effective in normalizing protein expression variations and monoamine content alterations in almost all brain areas analyzed. Pearson correlation tests display pattern variations both consequently to diet abstinence and pharmacological treatment. The results obtained from the present study are important in evidencing that palatable food exposure and subsequent abstinence can cause neuroadaptive changes that turn into the development of depression and anxiety, raising the importance of these comorbidities in obesity and palatable food consumption. Most importantly, we observe that enhancing the endogenous tone of acylethanolamides and endocannabinoids by blocking their enzymatic degradation might represent a novel protective strategy for psychiatric comorbidities in obese subjects.

Research products

11573/1680178 - 2023 - Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF ‐3845: A regional analysis of the contribution of endocannabinoid signaling machinery
De Ceglia, Marialuisa; Vittoria Micioni Di Bonaventura, Maria; Romano, Adele; Friuli, Marzia; Micioni Di Bonaventura, Emanuela; Gavito, Ana L.; Botticelli, Luca; Gaetani, Silvana; Rodríguez De Fonseca, Fernando; Cifani, Carlo - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF EATING DISORDERS (John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551) pp. - - issn: 0276-3478 - wos: WOS:000939633000001 (3) - scopus: 2-s2.0-85148899921 (3)

11573/1623482 - 2021 - Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice
Conte, E.; Romano, A.; De Bellis, M.; De Ceglia, M.; Carratu, M. R.; Gaetani, S.; Maqoud, F.; Tricarico, D.; Camerino, C. - 01a Articolo in rivista
paper: JOURNAL OF ENDOCRINOLOGY (Journal of Endocrinology Limited:17 18 Courtyard Woodlands, Bristol BS12 4NQ United Kingdom:011 44 117 9616046, EMAIL: sxa15@psu.edu, INTERNET: http://www.psu.edu, Fax: 011 44 117 9616071) pp. 135-148 - issn: 0022-0795 - wos: WOS:000641877100001 (8) - scopus: 2-s2.0-85105689581 (9)

11573/1687831 - 2021 - Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?
De Ceglia, Marialuisa; Decara, Juan; Gaetani, Silvana; Rodríguez De Fonseca, Fernando - 01a Articolo in rivista
paper: PHARMACEUTICALS (Basel : MDPI, Molecular Diversity Preservation International, 2004-) pp. 1002- - issn: 1424-8247 - wos: WOS:000712293900001 (9) - scopus: 2-s2.0-85116322892 (12)

11573/1402452 - 2020 - Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder
Romano, Adele; Micioni Di Bonaventura, Maria Vittoria; Gallelli, Cristina Anna; Koczwara, Justyna Barbara; Smeets, Dorien; Giusepponi, Maria Elena; De Ceglia, Marialuisa; Friuli, Marzia; Micioni Di Bonaventura, Emanuela; Scuderi, Caterina; Vitalone, Annabella; Tramutola, Antonella; Altieri, Fabio; Lutz, Thomas A; Giudetti, Anna Maria; Cassano, Tommaso; Cifani, Carlo; Gaetani, Silvana - 01a Articolo in rivista
paper: NEUROPSYCHOPHARMACOLOGY (Elsevier Science Incorporated / NY Journals:Madison Square Station, PO Box 882:New York, NY 10159:(212)633-3730, EMAIL: usinfo-f@elsevier.com, INTERNET: http://www.elsevier.com, Fax: (212)633-3680) pp. 1931-1941 - issn: 0893-133X - wos: WOS:000530976300002 (32) - scopus: 2-s2.0-85085874970 (34)

11573/1351998 - 2019 - “DEPRESSION AND ANXIETY AS OBESITY-RELATED COMORBIDITIES: POSSIBLE PROTECTIVE EFFECTS OF ACYLETHANOLAMIDES”
De Ceglia, M.; Romano, A.; Friuli, M.; Micioni Di Bonaventura, M. V.; Giusepponi, M. E.; Gallelli, C. A.; Koczwara, J. B.; Gavito, A. L.; Micioni Di Bonaventura, E.; Cassano, T.; Rodriguez De Fonseca, F.; Cifani, C.; Gaetani, S. - 04f Poster
conference: 20ª Reunión anual de la Sociedad Española de Investigación sobre Cannabinoides (SEIC): (Barcelona; Spain)
book: / - ()

11573/1344516 - 2018 - The selective inhibition of FAAH ameliorates cognitive decline, depressive-like symptoms and neurophatological alterations in a murine model of Alzheimer's disease
Calcagnini, Silvio; Bedse, Gaurav; Lavecchia, Angelo Michele; Caruso, Alessandra; Scaccianoce, Sergio; De Ceglia, Marialuisa; Gallelli, Cristina Anna; Romano, Adele; Cassano, Tommaso; Gaetani, Silvana - 04f Poster
conference: 28th Annual International Cannabinoid Research Society Symposium on the Cannabinoids, ICRS-2018 (Leiden (Olanda))
book: The selective inhibition of FAAH ameliorates cognitive decline, depressive-like symptoms and neurophatological alterations in a murine model of Alzheimer's disease - ()

11573/1344526 - 2018 - The selective inhibition of FAAH ameliorates cognitive decline, depressive-like symptoms and neuropathological alterations in a murine model of Alzheimer's disease
Calcagnini, Silvio; Bedse, Gaurav; Lavecchia, Angelo Michele; Caruso, Alessandra; Scaccianoce, Sergio; De Ceglia, Marialuisa; Gallelli, Cristina Anna; Romano, Adele; Cassano, Tommaso; Gaetani, Silvana - 04f Poster
conference: XXI National Seminar of the Italian Society of Pharmacology for PhD Students, Fellows, Post Doc and Specialist Trainees, XXI SIF seminar (Bresso (Milano))
book: The selective inhibition of FAAH ameliorates cognitive decline, depressive-like symptoms and neuropathological alterations in a murine model of Alzheimer's disease - ()

11573/1352000 - 2018 - "EFFECTS OF SUBDIAPHRAGMATIC DEAFFERENTATION ON OLEOYLETHANOLAMIDE INDUCED FOS EXPRESSION IN THE BRAIN"
De Ceglia, M.; Koczwara, J. B.; Gallelli, C. A.; Azari, E. K.; Arnold, M.; Romano, A.; Gaetani, S. - 04f Poster
conference: 21st SIF SEMINAR (Milano)
book: / - ()

11573/1352008 - 2018 - “ANTI-OBESITY EFFECTS OF OLEOYLETHANOLAMIDE IN A RODENT MODEL OF DIET INDUCED OBESITY”
De Ceglia, M.; Romano, A.; Rastelli, M.; Everard, A.; Koczwara, J. B.; Gallelli, C. A.; Cani, P. D.; Gaetani, S. - 04f Poster
conference: SINS PhD national meeting "New perspectives in Neuroscience: The Researches of Young Italian Neuroscientists”: (Napoli, Italia)
book: / - ()

11573/1186952 - 2018 - Modulation of the oxidative stress and lipid peroxidation by endocannabinoids and their lipid analogues
Gallelli, Cristina Anna; Calcagnini, Silvio; Romano, Adele; Koczwara, Justyna Barbara; De Ceglia, Marialuisa; Dante, Donatella; Villani, Rosanna; Giudetti, Anna Maria; Cassano, Tommaso; Gaetani, Silvana - 01a Articolo in rivista
paper: ANTIOXIDANTS (Basel: MDPI) pp. - - issn: 2076-3921 - wos: WOS:000440207400016 (66) - scopus: 2-s2.0-85050954409 (68)

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