Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

Abstract

Neurotensin (NT) is a neuropeptide identical in mice and humans that is produced and released in many CNS regions associated with maternal behavior. NT has been linked to aspects of maternal care and previous studies have indirectly suggested that endogenous NT signaling is altered in the postpartum period. In the present study, we directly examine whether NT and its receptors exhibit altered gene expression in maternal relative to virgin outbred mice using real time quantitative PCR (qPCR) across multiple brain regions. We also examine NT protein levels using anti-NT antibodies and immunohistochemistry in specific brain regions. In the medial preoptic area (MPOA), which is critical for maternal behaviors, mRNA of NT and NT receptor 3 (Sort1) were significantly up-regulated in postpartum mice compared to virgins. NT mRNA was also elevated in postpartum females in the bed nucleus of the stria terminalis dorsal. However, in the lateral septum, NT mRNA was down-regulated in postpartum females. In the paraventricular nucleus of the hypothalamus (PVN), Ntsr1 expression was down-regulated in postpartum females. Neurotensin receptor 2 (Ntsr2) expression was not altered in any brain region tested. In terms of protein expression, NT immunohistochemistry results indicated that NT labeling was elevated in the postpartum brain in the MPOA, lateral hypothalamus, and two subregions of PVN. Together, these findings indicate that endogenous changes occur in NT and its receptors across multiple brain regions, and these likely support the emergence of some maternal behaviors.

Song in an Affiliative Context Relates to the Neural Expression of Dopamine- and Neurotensin-Related Genes in Male European Starlings

“…Neurotensin (NT) is a candidate neuropeptide to modulate undirected song because it strongly interacts with dopaminergic signaling [Binder et al, 2001] and is implicated in social behavior [Driessen et al, 2014; Gammie et al, 2009; Merullo et al, 2015b; Merullo et al, 2015a] and learning [Azmi et al, 2006; Feifel et al, 2009; Keiser et al, 2014; Laszlo et al, 2010; Tirado-Santiago et al, 2006; Xiao et al, 2014]. NT and the NT1 receptor (NTR1; the only known avian NT receptor [Numao et al, 2011]) co-localize with DA neurons in the ventral tegmental area (VTA) and are also found in LS and Area X [Atoji et al, 1996; Binder et al, 2001; Merullo et al, 2015b; Merullo et al, 2015a; Xie et al, 2010].…”

Maternally responsive neurons in the bed nucleus of the stria terminalis and medial preoptic area: Putative circuits for regulating anxiety and reward

“…Apart from galanin, neurotensin-containing neurons in the mPOA may also promote maternal functions. Neurotensin mRNA is elevated within the mPOA and dorsal BNST of postpartum mice, but lowered in other regions, compared to virgins 114 . Neurotensin administration enhances Fos expression in the mPOA and dorsal BNST and suppresses maternal aggression 115 .…”

Neurotensin neural mRNA expression correlates with vocal communication and other highly-motivated social behaviors in male European starlings

“…It may be that as activity depletes NT stores, NT synthesis subsequently is upregulated to account for this depletion. NT mRNA is upregulated in the medial preoptic area of maternal mice [43], indicating that changes in NT expression may be involved in the control of agonistic behavior. The present results further support a role for NT in POM in agonistic interactions, though it is also possible that agonistic behaviors alter NT expression.…”

“…In addition to vocal behavior in starlings (reviewed above), NT in these regions has been implicated in the mediation of other social behaviors in rodents. In mice, NT expression in the medial preoptic area is associated inversely with maternal defense of offspring [41], intracerebroventricular injections of NT reduce this agonistic behavior and increase expression of the immediate early gene cFOS in the medial preoptic area and LS [42], and maternal mice demonstrate altered NT mRNA expression profiles in POM and LS [43]. These findings highlight that NT may be a neuromodulator for multiple social behaviors, including song.…”