Nk3R blockade has sex-divergent effects on memory in mice
Florido Torres, Antonio Luis (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)
Moreno, Estefanía (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular)
Canela, Enric I (Instituto de Salud Carlos III)
Andero Galí, Raül (Institució Catalana de Recerca i Estudis Avançats)

Data:	2022
Resum:	Memory consolidation is a process required for the formation of long-term memories. The G-protein-coupled receptor (GPCR) neurokinin-3-receptor (Nk3R) and its interactions with sex hormones seem important for the modulation of fear memory consolidation: Nk3R antagonism in male mice impairs fear memory, but enhances it in females. However, the involvement of the Nk3R as a modulator of other memories in both sexes remains unexplored. We use the novel object recognition paradigm to test the effect of a systemic blockade of Nk3R during memory consolidation. Further, we assess the expression of estrogen receptor α, estrogen receptor β, and androgen receptor and heterodimerization with Nk3R in the medial prefrontal cortex (mPFC) and dorsal hippocampus (DH) of mice. Nk3R systemic antagonism elicited decreased memory consolidation in males while it enhanced it in females during proestrus. Nk3R analysis in the different subregions of the mPFC and the DH showed a higher expression in males than females. Moreover, females presented upregulation of the androgen receptor in the CA1 and the estrogen receptor beta in the cingulate cortex, CA1, and dentate gyrus. Overall, males presented an upregulation of the estrogen receptor alpha. We also explored the heterodimerization of GCPR membrane sex hormone receptors with the Nk3R. We found a higher percentage of Nk3R-membrane G-protein estrogen receptors heterodimers in the prelimbic cortex of the mPFC in females, suggesting an interaction of estradiol with Nk3R in memory consolidation. However, males presented a higher percentage of Nk3R-membrane G-protein androgen receptors heterodimers compared to females, pointing to an interaction of testosterone with Nk3R in memory consolidation. These data propose novel ideas on functional interactions between Nk3R, sex hormones, estrogen receptors, and androgen receptors in memory consolidation.
Ajuts:	Agencia Estatal de Investigación SAF2016-76565-R Agencia Estatal de Investigación RYC2014-15784 Agencia Estatal de Investigación SAF2017-87629-R Agencia Estatal de Investigación PID2020-112705RB-I00 Ministerio de Ciencia, Innovación y Universidades ERANET Neuron JTC 2019 Instituto de Salud Carlos III AC19/00077 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018 FI_B00030
Nota:	Altres ajuts: National Alliance for Research on Schizophrenia and Depression: 22434 ; Fundación Alicia Koplowitz ; Centro de Investigación Biomédica en Red de Salud Mental CB19/09/00029
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Neurokinin-3 receptor ; Osanetant ; Sex differences ; Heterodimerization ; Estradiol ; Testosterone
Publicat a:	Biology of Sex Differences, Vol. 13 (june 2022) , ISSN 2042-6410

DOI: 10.1186/s13293-022-00437-z
PMID: 35690790

15 p, 1.7 MB

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