Early Paternal Deprivation Alters Levels of Hippocampal Brain-Derived Neurotrophic Factor and Glucocorticoid Receptor and Serum Corticosterone and Adrenocorticotropin in a Sex-Specific Way in Socially Monogamous Mandarin Voles

Abstract

In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels.

Fathering in rodents: Neurobiological substrates and consequences for offspring

“…Further, paternally deprived males showed no change in serum OT or in ERα in the MeA, and reductions of OTR in both the MeA and NAcc (Cao et al, 2014). Corticosterone in paternally deprived males did not change in one study (Wu et al, 2014a) and increased in two others (Wang et al, 2012; Yu et al, 2012). …”

“…In contrast, male mandarin voles did not display changes in GR or BDNF in dentate gyrus, or changes in ACTH (Wu et al, 2014a), and had enhanced expression of D1 and D2 in the NAcc (Yu et al, 2012), increased AVP-ir in the PVN, reduced AVP-ir in the anterior hypothalamus and reduced OT-ir in the PVN (Wang et al, 2012). Further, paternally deprived males showed no change in serum OT or in ERα in the MeA, and reductions of OTR in both the MeA and NAcc (Cao et al, 2014).…”

“…In females, paternal deprivation resulted in decreases in glucocorticoid receptors (GR) and brain-derived neurotrophic factor (BDNF) in the dentate gyrus (Wu et al, 2014a), increased serum levels of adrenocorticotrophin (ACTH) (Wu et al, 2014a), reduced levels of dopamine type 1 (D1) and type 2 (D2) receptors in the nucleus accumbens (Nacc) (Yu et al, 2012), reduced serum OT, and reduced ERα mRNA in the MeA, with no change in OTR mRNA in the MeA but a reduction in OTR mRNA in the Nacc (Cao et al, 2014). Corticosterone in paternally deprived females was higher than in pair-reared females in one study (Wu et al, 2014a) and lower in another (Yu et al, 2012). …”

“…Both sexes of paternally deprived mandarin voles displayed decreased levels of GR and BDNF in CA1 and CA 2/3 of the hippocampus (Wu et al, 2014a). Timelines of corticosterone and ACTH levels throughout early development (Wang et al, 2014) suggest that paternal deprivation alters development of these systems, including disruption of the stress-hyporesponsive period.…”

Paternal deprivation affects social behaviors and neurochemical systems in the offspring of socially monogamous prairie voles

“…All proteins were visualized on the ChemiDoc MP System (Bio-Rad). The specificities of the primary antibodies were validated in previous studies in voles as well as in rats and mice for the CRH system and H3k9ace, which share high homology with prairie voles (Huang et al, 2009; Greenberg et al, 2012; Gupta-Agarwal et al, 2012; Wang et al, 2013; Wu et al, 2014; Galinato et al, 2015; Duclot et al, 2016; Yadawa and Chaturvedi, 2016) . It should be mentioned that the OTR antibody was shown to be able to detect OTR protein in the vole brain tissue via antibody neutralization with an OTR blocking peptide but the signal reduction by overnight incubation with the blocking peptide was not complete (Duclot et al, 2016).…”