Long-lasting effects of postweaning sleep deprivation on cognitive function and social behaviors in adult mice.

Sleep deprivation (SD) has adverse effects on physical and mental health. Recently increasing attention has been given to SD in the early-life stage. However, the effects and mechanisms of postweaning SD on cognitive function and social behaviors are still unclear. In this study, SD was conducted in mice from postnatal Day 21 (PND21) to PND42, 6 h a day. Meanwhile, changes in body weight, food and water intake were continuously monitored. Behavioral tests were carried out in adulthood of mice. The levels of serum corticosterone, the proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines interleukin-10 (IL-10), vasopressin (VP) and oxytocin (OT) were measured by ELISA. Golgi staining was used to calculate neural dendritic spine density in the dorsal hippocampus (dHPC) CA1 region and medial prefrontal cortex (mPFC). We found that postweaning SD increased the food intake and the weight of female mice. Behavioral results showed that postweaning SD caused cognitive impairment and lowered social dominance in adult male mice but not in female mice. ELISA results showed that SD increased the levels of serum corticosterone, VP and OT in male mice and serum OT in female mice. Golgi staining analysis showed that SD decreased neural dendritic spine density in the dHPC in male mice. These results suggest that postweaning SD has a long-term effect on social dominance and cognitive function in male mice, which may provide a new insight into the role of SD in regulating cognitive function and social behaviors.

Maternal exposure to triclosan during lactation alters social behaviors and the hippocampal ultrastructure in adult mouse offspring.

We recently reported that exposure to triclosan (TCS), a broad-spectrum antibacterial agent, affects social behaviors in adult mice, however, the long-lasting effects of TCS exposure during early life on social behaviors are still elusive. The present study aimed to investigate the long-lasting impacts of adding TCS to the maternal drinking water during lactation on the social behaviors of adult mouse offspring and to explore the potential mechanism underlying these effects. The behavioral results showed that TCS exposure decreased body weight, increased depression-like behavior and decreased social dominance in both male and female offspring, as well as increased anxiety-like behavior and bedding preference in female offspring. In addition, enzyme-linked immunosorbent assay (ELISA) indicated that TCS exposure increased peripheral proinflammatory cytokine levels, altered serum oxytocin (OT) levels, and downregulated the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Morphological analysis by transmission electron microscopy (TEM) demonstrated that exposure to TCS induced morphological changes to synapses and neurons in the hippocampus of offspring. These findings suggested that TCS exposure during lactation contributed to abnormal social behaviors accompanied by increased peripheral inflammation and altered hippocampal neuroplasticity, which provides a deeper understanding of the effects of TCS exposure during early life on brain function and behavioral phenotypes.

Intracerebroventricular injection of sclerostin reduced social hierarchy and impaired neuronal dendritic complexity in mice.

An increasing number of studies have demonstrated extensive functional links between bone and the brain. As a novel endocrine organ, bone has received increasing attention for its upregulatory functions in the brain. Sclerostin, a novel bone-derived endocrine molecule, secreted by osteocytes, can inhibit the bone morphogenetic protein (BMP) and wingless/integrated (Wnt) signaling pathways to regulate bone formation, but its effects on the central nervous system and neurosocial behaviors are unknown. This study investigated the effects of intracerebroventricular sclerostin injection on social-emotional behaviors in adult mice. The results showed that acute elevation of sclerostin levels in the brain could induce anxiety-like behaviors and reduce the social hierarchy of mice while reducing the dendritic complexity of pyramidal neurons in the mouse hippocampus. These data suggested that sclerostin may regulate social-emotional behaviors, providing new evidence for the existence of a bone-brain axis, new insights into the regulation of social behaviors by bone-derived endocrine molecules, and a new direction for the study of individual emotional behavior regulation.

Inspiration for the prevention and treatment of neuropsychiatric disorders: New insight from the bone-brain-axis.

Bone is the main supporting structure of the body and the main organ involved in body movement and calcium and phosphorus metabolism. Recent studies have shown that bone is also a potential new endocrine organ that participates in the physiological and pathophysiological processes of the cardiovascular, digestive, and endocrine systems through various bioactive cytokines secreted by bone cells and bone marrow. Bone-derived active cytokines can also directly act on the central nervous system and regulate brain function and individual behavior. The bidirectional regulation of the bone-brain axis has gradually attracted attention in the field of neuroscience. This paper reviews the regulatory effects of bone-derived active cytokines and bone-derived cells on individual brain function and brain diseases, as well as the occurrence and development of related neuropsychiatric diseases. The central regulatory mechanism function is briefly introduced, which will broaden the scope for mechanistic research and help establish prevention and treatment strategies for neuropsychiatric diseases based on the bone-brain axis.