Neonatal treatment with ovarian hormones and suckling among distinct litter sizes: Differential effects on recognition memory and spreading depression at adulthood

Abstract

Objectives: Ovarian hormones (OH) and early malnutrition may affect the developing brain, with repercussions on behavioral and excitability-dependent processes. However, the possible synergistic effects of both factors have not been analyzed. In this study, we investigated the effect of treatment in early life with OH and suckling among distinct litter sizes on recognition memory, anxiety behavior, and the excitability-dependent phenomenon known as cortical spreading depression (CSD).

Methods: Female Wistar rats were suckled under favorable and unfavorable lactation, corresponding to litters with 9 and 15 pups (L₉ and L₁₅ groups, respectively). From postnatal days (P) 7 to 21, the animals received 50 µg/kg of β-estradiol or progesterone. From P80 to P84, we tested behavioral reactions. From P90 to P120, we analyzed CSD parameters.

Results: Compared with the corresponding L₉ groups, the OH-treated L₁₅ groups performed worse in recognition memory tasks. No intergroup difference in the anxiety parameters was observed. Compared with naive and vehicle-treated controls, OH-treated groups displayed higher CSD velocities and amplitudes and shorter CSD durations.

Discussion: Early treatment with OH facilitates recognition memory and CSD, and in association with unfavorable lactation (L₁₅) impaired recognition memory, but not anxiety behavior, in the adult brain. OH treatment and L₁₅ lactation condition seem to interact regarding OH action on memory, but not on CSD. Data suggest a long-lasting differential effect that might be related to the lasting hormonal action on brain excitability. We postulate and discuss the possibility that these findings may be implicated in human neurological diseases.

Keywords:

• Ovarian hormones
• Lactation conditions
• Brain development
• Neuronal excitability
• Cortical spreading depression
• Recognition memory

Disclaimer statements

Contributors None.

Funding This study was financially supported by CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (Edital 043/2013 Ciências do Mar II and BEX 2036/15-0), CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico, MS/SCTIE/DECIT (Nos. 17/2006, 303636/2014-9), and FACEPE - Fundação de Apoio à Ciência e Tecnologia de Pernambuco (IBPG-1002-2.07/11).

Conflicts of interest None.

Ethics approval None.

ORCID

Noranege Epifânio Accioly http://orcid.org/0000-0003-4636-9893

Rubem Carlos Araújo Guedes http://orcid.org/0000-0002-2396-4019