Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

Abstract

Parental experience imposes neuroplasticity in the hippocampus of females and males. In lactating rat dams, the hippocampus is protected against excitotoxic damage by kainic acid lesioning, although it is still unknown whether paternity can provide such protection to male rodents. To evaluate the protective effects of fatherhood against excitotoxic lesions, we paired male mice with females and co‐housed them until the day of parturition (PPD0), when we randomly assigned them to two groups: (i) the pregnancy group (males housed individually overnight and injected i.c.v. with 100 ng per 1 μL of kainic acid or vehicle on PPD1) and (ii) the sire group (males housed with the dam and pups until PPD8, when injected i.c.v. after evaluation of parental behaviour). Individually housed virgin adult male mice formed the control group. Markers of neurodegeneration (NeuN, Fluoro‐Jade C) and astrogliosis (glial fibrillary acidic protein) were evaluated in fixed cerebral tissue containing the dorsal CA1, CA3 and CA4 hippocampal subfields. The CA1 subfield did not suffer damage in any of the experimental groups. The sire group exhibited less neurodegeneration and astrogliosis in the CA3 and CA4 subfields compared to their respective controls, independently of the expression of parental behaviour. Western blot analysis was conducted for prolactin (PRL), PRL receptor and related intracellular pathways. Monomeric PRL was lower in the hippocampus of sires in the first week postpartum with a parallel rise of a 48‐kDa dimerised isoform compared to virgin controls. The long isoform of PRL receptor did not change, and signal transducer and activator of transcription 5 (STAT5) was not detected in the hippocampus. However, a sustained rise in pAkt, a signalling molecule that participates in cell survival, was observed in the sire group. These results indicate that the hippocampus of sires housed with the dam and pups is less sensitive to neurotoxic injury, which might not be primarily regulated by PRL‐STAT5‐modulated mechanisms.

Plasticity of the paternal brain: Effects of fatherhood on neural structure and function

“…The number and location of cells expressing these markers are measured in fathers and in males with varying amounts of interaction with females and/or pups to tease apart which aspects of the transition into fatherhood contribute to changes in neurogenesis and cell survival. While most research on neurogenesis focuses on the hippocampus (Anagnostou & Morales, 2019; Glasper et al, 2011; Hyer et al., 2016, 2017; Lieberwirth et al., 2013; Mak & Weiss, 2010), some studies have investigated the olfactory bulbs (Mak & Weiss, 2010), amygdala (Lieberwirth et al., 2013), and hypothalamus (Lieberwirth et al., 2013), areas associated with memory, emotion, and detection of and response to stimuli from pups.…”

“…While most research on neurogenesis focuses on the hippocampus (Anagnostou & Morales, 2019;Glasper et al, 2011;Hyer et al, 2016Lieberwirth et al, 2013;Mak & Weiss, 2010), some studies have investigated the olfactory bulbs (Mak & Weiss, 2010), amygdala (Lieberwirth et al, 2013), and hypothalamus (Lieberwirth et al, 2013), areas associated with memory, emotion, and detection of and response to stimuli from pups. Mak and Weiss (2010) examined effects of fatherhood in the facultatively biparental house mouse, in which fathers do not provide infant care under natural conditions but do so when housed individually with pups or with their mate and pups in the laboratory (Gandelman et al, 1970;McCarthy & vom Saal, 1986).…”

Living with female rats exposed to restraint stress during pregnancy caused depressive‐like behavior in male rats and stress‐induced apoptosis

“…However, while most emphasis is on the effects of prenatal stress on maternal behavior, more research is needed on how maternal depressive-like behaviors affect male partners. For instance, Anagnostou and Morales (2019) show that paternal interaction with the pups and the dam induces neuroprotection against neurotoxin lesioning in the hippocampus of male mice. Considering the direct effects of paternal behavior even on the individual's brain, the behavioral and cognitive health of both parents participating in the care of offspring is important for the development of the generations.…”