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

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.