Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior.

Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.

Addition of l-carnitine to the freezing extender improves post-thaw sperm quality of Okinawan native Agu pig.

The objective of the present study was to establish whether the addition of l-carnitine (LC), which exhibits antioxidant activity, to the freezing extender improves the quality of cryopreserved Okinawan native Agu pig sperm. Ejaculated sperm frozen in an extender supplemented with 0, 1, 2.5, or 5 mM LC was thawed, and the integrities of mitochondria and the plasmalemma and other sperm characteristics were evaluated. The treatment with different concentrations of LC effectively improved sperm motility, mitochondrial and plasmalemmal integrities, and the proteolytic activity of acrosomal contents after freeze-thawing (P < 0.05). The proportion of post-thaw sperm possessing intact mitochondria and plasmalemma and higher proteolytic activity of acrosomal contents was markedly higher among sperm frozen in the presence of 2.5 mM LC than among sperm frozen in the extender without LC (P < 0.05). Furthermore, although the addition of LC to the freezing extender had no effect on disturbance of DNA damage and caspase activity, sperm treated with 2.5 mM LC during freezing exhibited significantly higher penetrability into matured oocytes in vitro than untreated sperm. Collectively, these results indicate that the addition of LC to the freezing extender effectively improved the post-thaw quality of Agu pig sperm by preventing mitochondrial dysfunction caused by oxidative stress during cryopreservation.

Endoplasmic reticulum stress attenuation promotes bovine oocyte maturation in vitro.

We have previously reported that regulation of endoplasmic reticulum (ER) stress during in vitro culture acutely increases bovine embryo developmental rate and cryotolerance; these data indicate that ER stress is a critical factor reducing the quality of in vitro-produced embryos. In the current follow-up study, we examined whether ER stress attenuation during in vitro maturation influences meiotic maturation, oocyte quality, and subsequent embryonic development. Bovine cumulus oocyte complexes (COCs) derived from slaughterhouse ovaries were matured with or without tauroursodeoxycholic acid (TUDCA), a selective inhibitor of ER stress (0, 50, 100, and 200 µM) for 22 h followed by in vitro fertilization, and zygotes were cultured for 8 days. Of the different doses of TUDCA, 100 µM TUDCA significantly increased the maturation rate, and decreased reactive oxygen species in denuded oocytes, and appeared lower number of apoptotic cells in matured COCs. Subsequently, treatment of TUDCA (100 µM) decreased the localization and amount of GRP78/BIP protein level as well as ER stress (GRP78/BIP, PERK, IER1, ATF4, and XBP1) and apoptosis (CHOP and BAX)-related gene expression, while it increased the anti-apoptotic gene BCL2 level in matured COCs. Moreover, addition of TUDCA (100 µM) during IVM significantly improved the blastocyst formation rate (43.6 ± 1.8% vs 49.7 ± 1.3%) and decreased the number of apoptotic cells (7.7 ± 1.1% vs 5.03 ± 0.6%) in blastocysts. These findings suggest that the presence of ER stress during maturation impairs the developmental competence of bovine COCs and that this process can be reversed by TUDCA.