Major depressive disorder (MDD) is a chronic, recurring, and potentially life-threatening illness, which affects over 300 million people worldwide. MDD affects not only the emotional and social domains but also cognition. However, the currently available treatments targeting cognitive deficits in MDD are limited. Minocycline, an antibiotic with anti-inflammatory properties recently identified as a potential antidepressant, has been shown to attenuate learning and memory deficits in animal models of cognitive impairment. Here, we explored whether minocycline recovers the deficits in cognition in a mouse model of depression. C57BL6/J adult male mice were exposed to two weeks of chronic unpredictable mild stress to induce a depressive-like phenotype. Immediately afterward, mice received either vehicle or minocycline for three weeks in standard housing conditions. We measured anhedonia as a depressive-like response, and place learning to assess cognitive abilities. We also recorded long-term potentiation (LTP) as an index of hippocampal functional plasticity and ran immunohistochemical assays to assess microglial proportion and morphology. After one week of treatment, cognitive performance in the place learning test was significantly improved by minocycline, as treated mice displayed a higher number of correct responses when learning novel spatial configurations. Accordingly, minocycline-treated mice displayed higher LTP compared to controls. However, after three weeks of treatment, no difference between treated and control animals was found for behavior, neural plasticity, and microglial properties, suggesting that minocycline has a fast but short effect on cognition, without lasting effects on microglia. These findings together support the usefulness of minocycline as a potential treatment for cognitive impairment associated with MDD.

Minocycline treatment improves cognitive and functional plasticity in a preclinical mouse model of major depressive disorder / Poggini, Silvia; Lopez, Maria Banqueri; Albanese, Naomi Ciano; Golia, Maria Teresa; Ibáñez, Fernando González; Limatola, Cristina; Furhmann, Martin; Lalowski, Maciej; Tremblay, Marie-Eve; Maggi, Laura; Kaminska, Bozena; Branchi, Igor. - In: BEHAVIOURAL BRAIN RESEARCH. - ISSN 1872-7549. - 441:(2023), p. 114295. [10.1016/j.bbr.2023.114295]

Minocycline treatment improves cognitive and functional plasticity in a preclinical mouse model of major depressive disorder

Poggini, Silvia;Albanese, Naomi Ciano;Golia, Maria Teresa;Limatola, Cristina;Maggi, Laura;Branchi, Igor
2023

Abstract

Major depressive disorder (MDD) is a chronic, recurring, and potentially life-threatening illness, which affects over 300 million people worldwide. MDD affects not only the emotional and social domains but also cognition. However, the currently available treatments targeting cognitive deficits in MDD are limited. Minocycline, an antibiotic with anti-inflammatory properties recently identified as a potential antidepressant, has been shown to attenuate learning and memory deficits in animal models of cognitive impairment. Here, we explored whether minocycline recovers the deficits in cognition in a mouse model of depression. C57BL6/J adult male mice were exposed to two weeks of chronic unpredictable mild stress to induce a depressive-like phenotype. Immediately afterward, mice received either vehicle or minocycline for three weeks in standard housing conditions. We measured anhedonia as a depressive-like response, and place learning to assess cognitive abilities. We also recorded long-term potentiation (LTP) as an index of hippocampal functional plasticity and ran immunohistochemical assays to assess microglial proportion and morphology. After one week of treatment, cognitive performance in the place learning test was significantly improved by minocycline, as treated mice displayed a higher number of correct responses when learning novel spatial configurations. Accordingly, minocycline-treated mice displayed higher LTP compared to controls. However, after three weeks of treatment, no difference between treated and control animals was found for behavior, neural plasticity, and microglial properties, suggesting that minocycline has a fast but short effect on cognition, without lasting effects on microglia. These findings together support the usefulness of minocycline as a potential treatment for cognitive impairment associated with MDD.
2023
Antidepressant; Cognition; Microglia; Minocycline; Neural plasticity; Stress response
01 Pubblicazione su rivista::01a Articolo in rivista
Minocycline treatment improves cognitive and functional plasticity in a preclinical mouse model of major depressive disorder / Poggini, Silvia; Lopez, Maria Banqueri; Albanese, Naomi Ciano; Golia, Maria Teresa; Ibáñez, Fernando González; Limatola, Cristina; Furhmann, Martin; Lalowski, Maciej; Tremblay, Marie-Eve; Maggi, Laura; Kaminska, Bozena; Branchi, Igor. - In: BEHAVIOURAL BRAIN RESEARCH. - ISSN 1872-7549. - 441:(2023), p. 114295. [10.1016/j.bbr.2023.114295]
File allegati a questo prodotto
File Dimensione Formato  
2023_Minocycline treatment improves cognitive and functional plasticity in a preclinical mouse model of major depressive disorder.pdf

solo gestori archivio

Note: Poggini_Minocycline treatment_2023
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 2.77 MB
Formato Adobe PDF
2.77 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1672776
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 2
social impact