Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual's life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS+SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS+SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS+SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS+SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS+SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MS+SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region.

Early-life stress has long-lasting effects on neuroendocrine and behaviour in adulthood. Maternal separation (MS) is used as a model of early-life stress and daily repeated MS (RMS) for 3 h during the first two postnatal weeks is widely used in rodent studies. However, it is not fully understood whether early-life animals desensitise/habituate to repeated stress. In the present study, we investigated the effects of daily RMS for 3 h and acute/single time MS (SMS) for 3 h on the plasma corticosterone level and c-Fos expression in the brain in mice at different postnatal ages. Mice were subjected to: (i) RMS from postnatal day (PND) 1 to 14 (RMS14); (ii) RMS from PND14 to 21 (RMS21); (iii) SMS on PND14 (SMS14); and (iv) SMS on PND21 (SMS21). Plasma corticosterone and c-Fos expression were examined on the final day in each experiment. The basal corticosterone levels in RMS14 and RMS21 were equal to those in respective age-matched controls. After the final separation, the levels were significantly increased and were comparable with those after SMS14 and SMS21, respectively. Histological analysis indicated that c-Fos expression significantly increased in many brain regions, including the paraventricular nucleus, prefrontal cortex, hippocampus, and basolateral and medial amygdale in both SMS14 and SMS21 mice. However, c-Fos expression in RMS14 mice significantly increased in many regions, whereas such increases were hardly seen in RMS21 mice. These results indicate that repeated early-life stress neither increases basal corticosterone, nor decreases the magnitude of the corticosterone response during the first three postnatal weeks, although desensitisation of c-Fos expression induced by repeated stress is changed during postnatal development.

To elucidate compositional changes of the pineal body with aging, the authors investigated age-related changes of elements in the pineal body. After the ordinary dissection by medical students was finished, the pineal bodies and seven arteries were resected from the subjects ranging in age from 58 to 94 years. The element contents were determined by inductively coupled plasma atomic emission spectrometry. It was found that a high accumulation of Ca and P occurred in the pineal bodies with aging. Regarding the relationships among the elements, it was found that there were significant direct correlations among the contents of Ca, P, and Mg. With regard to the relationships between the pineal body and the arteries, no significant correlations were found in the Ca content between the pineal body and the arteries, such as the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, and common iliac arteries.

To elucidate compositional changes of the corpus callosum with aging, the authors investigated age-related changes of elements and relationships with their element contents in the corpus callosum. After ordinary dissection by medical students at Nara Medical University was finished, the genu, trunk, and splenium of the corpus callosum were resected from the subjects ranging in age from 58 to 94 years. The element contents of the corpus callosum were determined by inductively coupled plasma-atomic emission spectrometry. The contents of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the genu, trunk, and splenium of the corpus callosum with aging. Regarding the relationships among the element contents, significant correlations were found among the contents of Ca, P, S, Mg, and Fe in all of the genu, trunk, and splenium of the corpus callosum with some exceptions.

An anomalous left hepatic vein opening independently of the coronary sinus into the right atrium was found in the cadaver of an 88-year-old Japanese man. This vein originated from the left lobe of the liver, perforated the diaphragm at the left side of the vena caval foramen and opened into the right atrium. The left hepatic vein anastomosed mutually with the middle hepatic vein at the level of venule. The ligamentum venosum originated from the left branch of the portal vein and was connected directly to the left hepatic vein. The development of the central systemic venous system and a possible explanation for the morphogenesis of this anomaly were reviewed. As a result, the occurrence of this anomalous vein was explained as being due to the persistence of the left vitelline connection with the left sinus horn and the ductus venosus.