Lactation Reduces Glial Activation Induced by Excitotoxicity in the Rat Hippocampus

Abstract

Motherhood induces a series of adaptations in the physiology of the female, including an increase of maternal brain plasticity and a reduction of cell damage in the hippocampus caused by kainic acid (KA) excitotoxicity. We analysed the role of lactation in glial activation in the hippocampal fields of virgin and lactating rats after i.c.v. application of 100 ng of KA. Immunohistochemical analysis for glial fibrillary acidic protein (GFAP) and ionised calcium binding adaptor molecule 1 (Iba-1), which are markers for astrocytes and microglial cell-surface proteins, respectively, revealed differential cellular responses to KA in lactating and virgin rats. A significant astrocyte and microglial response in hippocampal areas of virgin rats was observed 24 h and 72 h after KA. By contrast, no increase in either GFAP- or Iba-1-positive cells was observed in response to KA in the hippocampus of lactating rats. Western blot analysis of GFAP showed an initial decrease at 24 h after KA treatment, with an increase at 72 h in the whole hippocampus of virgin but not of lactating rats. The number of GFAP-positive cells was increased by lactation in the dentate gyrus of the hippocampus but not in CA1 and CA3 areas. The present results indicate that lactating rats exhibit diminished responses of astrocyte and microglial cells in the hippocampus to damage induced by KA, supporting the notion that the maternal hippocampus is resistant to excitotoxic insults.

An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period

“…For example, progesterone has been found to be anti-inflammatory in the face of an ischemic challenge, nerve damage, or even infection (Brotfain et al, 2016; Kipp et al, 2016; Labombarda et al, 2015; Lammerding et al, 2016; Paris et al, 2016; Perez-Alvarez and Wandosell, 2016). Additionally, during lactation, progesterone contributes to an increase in astrocytes in the rodent cingulate cortex (Salmaso et al, 2009) and the dentate gyrus of the hippocampus (Cabrera et al, 2013). Therefore it is very likely that high levels of progesterone associated with pregnancy can impact the function of glial cells, including microglia, thereby altering the expression of cytokines throughout pregnancy and the postpartum period (Posillico and Schwarz, 2016).…”

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

“…Research in our laboratory has used the postpartum period of lactation as a model of physiological hyperprolactinaemia and has shown that the rat dam is less sensitive to neurotoxic damage during lactation than virgin conspecifics. More specifically, the dam presents a significant local up‐regulation of antiapoptotic protein Bcl‐2 levels compared to dioestrus virgin rats under basal conditions, and lower cell death (FJC) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling), no significant loss of neurones (NeuN), lower astrogliosis, and reduced microglial response (GFAP and Iba1 fluorescence levels and Scholl morphometric analysis of individual astrocytes) after both peripheral and central administration of KA . Some of these effects are attributed to PRL, which is highly expressed during lactation and has been shown to have protective effects in both in vivo and in vitro experiments …”

“…Motherhood induces changes in the hippocampus that support the expression and maintenance of parental care behaviours . Regarding the neuroprotective effects of motherhood, we have previously reported that the hippocampus of the lactating dam is resistant to the damaging action of the excitotoxin kainic acid (KA), administered centrally or peripherally . The protective effect of the rat dam against excitotoxic lesions also has been documented by other groups .…”

Hormonal influences on neuroimmune responses in the CNS of females

“…Moreover, they increase neurogenesis within the subgranular zone of the dentate gyrus and subventricular zone (Pawluski et al, 2009), and induce regenerative responses in a mouse model of Alzheimer’s disease (Pike et al, 2009; Borowicz et al, 2011). During lactation, progesterone participates in glial changes in brain areas such as the cingulate cortex (Salmaso et al, 2009) and the dentate gyrus of the hippocampus (Cabrera et al, 2013), and this steroid is part of the hormonal cocktail responsible for diminished responses of astrocyte and microglial cells in the hippocampus of lactating rats to damage induced by excitotoxic insults (Cabrera et al, 2013). …”