Pregnancy and Maternal Behavior Induce Changes in Glia, Glutamate and Its Metabolism within the Cingulate Cortex

Abstract

An upregulation of the astrocytic proteins GFAP and bFGF within area 2 of the cingulate cortex (Cg2) occurs within 3 hours of parturition in rats. These changes are the result of an interaction between hormonal state and maternal experience and are associated with increased dendritic spine density in this area. Here, we examined whether this upregulation of astrocytic proteins generalized to other glial markers and, in particular those associated with glutamate metabolism. We chose glial markers commonly used to reflect different aspects of glial function: vimentin, like GFAP, is a marker of intermediate filaments; glutamine synthetase (GS), and S-100beta, are used as markers for mature astrocytes and GS has also been used as a specific marker for glutamatergic enzymatic activity. In addition, we examined levels of proteins associated with glutamine synthetase, glutamate, glutamine and two excitatory amino acid transporters found in astrocytes, glt-1 and glast. S100beta immunoreactivity did not vary with reproductive state in either Cg2 or MPOA suggesting no change in the number of mature astrocytes across these conditions. Vimentin-ir did not differ across groups in Cg2, but expression of this protein decreased from Day 1 postpartum onwards in the MPOA. By contrast, GS-ir was increased within 24 h postpartum in Cg2 but not MPOA and similarly to GFAP and bFGF this upregulation of GS resulted from an interaction between hormonal state and maternal experience. Within Cg2, upregulation of GS was not accompanied by changes in the astrocytic glutamatergic transporters, glt-1 and glast, however, an increase in both glutamate and glutamine proteins were observed within the Cg2 of postpartum animals. Together, these changes suggest postpartum upregulation of glutamatergic activity and metabolism within Cg2 that is stimulated by pregnancy hormones and maternal experience.

The birth of new neurons in the maternal brain: Hormonal regulation and functional implications

“…The neural modifications found in the maternal brain are numerous and widespread (Figure 1) consisting of neurochemical, neuroendocrine, activational, morphological, gene expression and functional changes within a distributed but interconnected circuitry (Theodosis et al, 1986; Xerri et al, 1994; Featherstone et al, 2000; Keyser-Marcus et al, 2001; Tomizawa et al, 2003; Rasia-Filho et al, 2004; Febo et al, 2005; Miranda and Liu, 2009; Sanna et al, 2009; Leuner et al, 2010; Canavan et al, 2011; Salmaso et al, 2011a; Salmaso et al, 2011b; Lonstein et al, 2014; Bridges, 2015; Cohen and Mizrahi, 2015; Corona and Levy, 2015; Elyada and Mizrahi, 2015) that includes the hypothalamus, amygdala, nucleus accumbens, olfactory bulb, hippocampus and various cortical areas (i.e. parietal, auditory, somatosensory, prefrontal).…”

Glutamate, GABA, and glutamine are synchronously upregulated in the mouse lateral septum during the postpartum period

“…The mechanisms underlying such a critical remodeling of the brain are complex and include changes in gene expression, synaptic plasticity, neurogenesis, morphology, structure, metabolism, and neurochemistry (Kinsley, 2008; Moltz et al, 1975; Salmaso et al, 2011; Shingo et al, 2003; Zhao et al, 2012a). Glutamate and GABA are critical excitatory and inhibitory CNS neurotransmitters and are involved in a broad variety of physiological events, including synaptic plasticity, neuroendocrine function, learning and memory, cell proliferation, and differentiation (Carver and Reddy, 2013; Ciceroni et al, 2010; Durand et al, 2008; Ogden et al, 2014; Zuure et al, 2013).…”

Metabotropic Glutamate Receptor 3 Is Downregulated and Its Expression Is Shifted From Neurons to Astrocytes in the Mouse Lateral Septum During the Postpartum Period

“…The selective shift in mGluR3 expression from neurons to astrocytes in postpartum LSI may participate in these behavioral processes during the postpartum period. To date, it is not clear what functional role such a shift will have, but one possibility is that elevated mGluR3s in glial cells supports the significant glial changes in the postpartum state, including morphology, structure and function (Theodosis and Poulain 1984;Featherstone et al 2000;Salmaso et al 2005;Salmaso et al 2011).…”