Journal Article

DZNE-2023-00155

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Minocycline treatment improves cognitive and functional plasticity in a preclinical mouse model of major depressive disorder.

Poggini, S. ; Lopez, M. B. ; Albanese, N. C. ; Golia, M. T. ; Ibáñez, F. G. ; Limatola, C. ; Fuhrmann, M.DZNE* ; Lalowski, M. ; Tremblay, M.-E. ; Maggi, L. ; Kaminska, B. ; Branchi, I.

2023
Elsevier Amsterdam

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Please use a persistent id in citations: doi:10.1016/j.bbr.2023.114295  doi:10.60944/dzne-2023-00155

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.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Male (MeSH) ; Minocycline: pharmacology (MeSH) ; Depressive Disorder, Major: drug therapy (MeSH) ; Anti-Bacterial Agents: pharmacology (MeSH) ; Cognition Disorders (MeSH) ; Cognition (MeSH) ; Hippocampus (MeSH) ; Minocycline ; antidepressant ; cognition ; microglia ; minocycline ; neural plasticity ; stress response ; Anti-Bacterial Agents

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Contributing Institute(s):

1. Neuroimmunology and Imaging (AG Fuhrmann)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Green Open Access ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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