Topical cortical application of ovarian hormones and modulation of brain electrical activity: analysis of spreading depression in well-nourished and malnourished female rats

ABSTRACT

Objectives – Clinical and experimental evidence indicates that both ovarian hormones and nutritional condition can affect several brain functions, including those depending on excitability mechanisms. Nutritional deficiency, on the other hand, is capable of disturbing brain structure and function of mammals. We have previously demonstrated that ovariectomy decelerates [Accioly NE, Benevides R, Costa B, Guedes RCA. Ovariectomy in the developing rat decelerates cortical spreading depression in adult brain. Internat J Develop Neurosci. 2012;30:405–410.], whereas systemic hormone administration accelerates the excitability-dependent phenomenon known as cortical spreading depression (CSD; [Accioly NE, Guedes RCA. Neonatal treatment with ovarian hormones and suckling among distinct litter sizes: Differential effects on recognition memory and spreading depression at adulthood. Nutr Neurosci. 2017;1–11. doi:10.1080/1028415X.2017.1358472.]). In this study we investigated the interaction between topical cortical treatment with ovarian hormones and malnutrition during lactation on CSD parameters.

Methods – Female Wistar rats were suckled in litters with 6–9 or 12–15 pups (L₉ and L₁₅ groups; normal size- and large size litters, respectively). At postnatal days 90–120, estradiol (5, 10 and 20 mg/ml solutions) and progesterone (66 mg/ml, 132 mg/ml and 264 mg/ml solutions) were topically applied during a CSD recording session. CSD parameters (propagation velocity, and amplitude and duration of the CSD DC-shift) were calculated before and after CSD.

Results – Topical applications of estradiol and progesterone reversibly and dose- dependently accelerated CSD, and decreased duration and increased amplitude of the CSD DC-shift (p < 0.05); furthermore, unfavorable lactation (L₁₅) accelerated CSD in adulthood.

Discussion – In support of our previous studies with systemic hormone treatment, topical cortical application of ovarian hormones modulates CSD in the adult brain, suggesting a cortically-based mechanism for this effect, which might be related to the hormonal action on synaptic transmission with consequent modulation of brain excitability.

KEYWORDS:

• Estradiol
• progesterone
• early undernutrition
• brain excitability
• cortical spreading depression
• female rats

Acknowledgements

This study was financially supported by CAPES (Procad/2007), CNPq (INCT de Neurociencia Translacional–No. 573604/2008-8), MS/SCTIE/DECIT (No. 17/2006), FACEPE (APQ0975-4.05/08), and IBN-Net/Finep (No. 4191). R.C.A. Guedes is Research Fellow from CNPq (No. 301190/2010-0).

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Noranege Epifânio Accioly has graduated in Physiotherapy at Universidade de Ciencias da Saude de Alagoas, Brazil, with a Master’s degree and PhD degree both in Biochemstry and Physiology at Universidade Federal de Pernambuco, Brazil.

Rubem Carlos Araújo Guedes has graduated in Human Medicine from Universidade Federal de Pernambuco, Brazil, with a Master’s degree in Biophysics at Universidade Federal do Rio de Janeiro, Brazil, and a PhD degree in Human Medicine at the University of Göttingen, Germany. She is Full Professor at the Department of Nutrition, Universidade Federal de Pernambuco, Brazil. She is former supervisor of Dr Accioly during her M.S. and Ph.D. courses.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico: [Grant Number MS/SCTIE/DECIT (Nos. 17/2006, 303636/2014-9)]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior: [Grant Number Finance Code 001 – Edital 043/2013 Ciencias Do Mar II and BEX 2036/15-0]; INCT-Instituto Nacional de Ciencia e Tecnologia em Excitoxicidade e Neuroprotecao: [Grant Number Edital INCT/MCT/CNPq)]; FACEPE-Fundaco de Apoio a Ciencia e Tecnologia de Pernambuco: [Grant Number (IBPG-1002- 2.07/11)].