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Synergistic neuroprotective action of prolactin and 17β-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats

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Abstract

Purpose

The neuroprotective actions of the ovarian hormone 17β-estradiol (E2) against different brain lesions have been constantly confirmed in a variety of models including kainic acid (KA) lesions. Similarly, the pituitary hormone prolactin (PRL), traditionally associated with lactogenesis, has recently been linked to a large diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 as regards its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The current study aimed to investigate whether the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated with changes in hippocampal neuronal density.

Methods

Ovariectomized (OVX) rats were treated with saline, PRL, and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Memory was evaluated with the novel object recognition test (NOR).

Results

On their own, both PRL and E2 prevented short- and long-term memory deficits in lesioned animals and exerted neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior to either of the treatments administered alone as regards improving both memory and neuronal survival.

Conclusion

Taken together, these results point to a synergic effect of E2 and PRL in the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.

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Acknowledgements

This study was partially supported by CONACYT (286446), COFAA, SIP-IPN, and DGAPA PAPIIT UNAM, grant numbers IN224019 to GRR and IN227123, to JPM.

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Authors and Affiliations

  1. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Sto. Tomás, 11340. Ciudad de México, Ciudad de México, México

    Karen De la Torre, José Eduardo Suárez-Santiago & Ofir Picazo

  2. Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México

    Marco Antonio Cerbón & Gladys Molina-Salinas

  3. Facultad de Medicina Humana, Universidad Autónoma de Chiapas, Tuxtla Gutiérrez, Chiapas, Mexico

    José Eduardo Suárez-Santiago

  4. Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México

    Jean-Pascal Morin & Gabriel Roldán-Roldán

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  1. Karen De la Torre
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  2. Marco Antonio Cerbón
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Correspondence to Gabriel Roldán-Roldán or Ofir Picazo.

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Research involving human participants and/or animals

All experimental procedures were performed in accordance with the guidelines and standards established by the Ethics Committee of the Faculty of Medicine, UNAM, Mexico City, project registration number FM/DI/046/2018 and by the Internal Committee for Use and Care of Laboratory Animals No. 006/CIC/2018.

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De la Torre, K., Cerbón, M.A., Molina-Salinas, G. et al. Synergistic neuroprotective action of prolactin and 17β-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats. Hormones (2024). https://doi.org/10.1007/s42000-024-00551-0

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