Altered dorsal functional connectivity after post-weaning social isolation and resocialization in mice.

BACKGROUND: Social isolation (SI) leads to various mental health disorders. Despite abundant studies on behavioral and neurobiological changes induced by post-weaning SI, the characterization of its imaging correlates, such as resting-state functional connectivity (RSFC), is critically lacking. In addition, the effects of resocialization after isolation remain unclear. Therefore, this study aimed to explore the effects of 1) SI on cortical functional connectivity and 2) subsequent resocialization on behavior and functional connectivity. METHODS: Behavioral tests were conducted to validate the post-weaning SI mouse model, which is isolated during the juvenile period. Wide-field optical mapping was performed to observe both neuronal and hemodynamic signals in the cortex under anesthesia. Using seed-based and graph theoretical analyses, RSFC was analyzed. SI mice were then resocialized and the array of behavior and imaging tests was conducted. RESULTS: Behaviorally, SI mice showed elevated anxiety, social preference, and aggression. RSFC analyses using the seed-based approach revealed decreased cortical functional connectivity in SI mice, especially in the frontal region. Graph network analyses demonstrated significant reduction in network segregation measures. After resocialization, mice exhibited recovered anxiogenic and aggressive behavior, but RSFC data did not show significant changes. CONCLUSIONS: We observed an overall decrease in functional connectivity in SI mice. Moreover, resocialization restored the disruptions in behavioral patterns but functional connectivity was not recovered. To our knowledge, this is the first study to report that, despite the recovering tendencies of behavior in resocialized mice, similar changes in RSFC were not observed. This suggests that disruptions in functional connectivity caused by social isolation remain as long-term sequelae.

Intermittent Fasting Alleviates Cognitive Impairments and Hippocampal Neuronal Loss but Enhances Astrocytosis in Mice with Subcortical Vascular Dementia.

BACKGROUND: Intermittent fasting (IF) is found to exhibit neuroprotection against various insults, including ischemia; however, IF has been mainly applied before disease onset. It remains unknown whether IF implementation alleviates the long-term detrimental effects of a disease after its establishment. OBJECTIVES: To investigate the IF effects on cognitive impairments and cerebrovascular pathologies in a subcortical vascular dementia (SVaD) mouse model. METHODS: The SVaD model was developed by inducing hypoperfusion and hyperlipidemia in apoE-deficient (apoE-/-) mice. We subjected 10-week-old apoE-/- mice to bilateral common carotid artery stenosis using micro-coils after they were fed a high-fat diet (HFD; 45% energy) for 6 weeks to induce hyperlipidemia. Age-matched wild-type C57BL/6J mice received sham surgery after undergoing an identical HFD treatment. Both the SVaD model and wild-type mice either started a 1-month IF regimen (time-restricted feeding for 6 hours per day) or continued the standard diet ad libitum (6.2% fat energy) at 8 weeks post-surgery. We assessed mice weight, food intake, and outcomes in a behavioral test battery before, during, and after the IF regimen, prior to histopathological analyses (microvessel density, neuronal density, white matter damage, astrocytosis) of their brains. RESULTS: SVaD model mice on the IF regimen (SVaD-IF) exhibited higher mean recognition and spatial working memory performance compared to SVaD mice fed ad libitum (SVaD-AL; P < 0.01). Additionally, SVaD-IF mice had ∼5% higher hippocampal neuronal density in the dentate gyrus (DG) and cornu ammonis 1 regions than SVaD-AL mice (P < 0.001), which paralleled their post-IF cognitive enhancements. However, SVaD-IF mice showed an ∼50% increase in hippocampal DG astrocytosis compared to SVaD-AL mice (P < 0.05), with no significant differences in microvessel densities among the 2 groups. CONCLUSIONS: The improvements in SVaD-IF mice suggest that IF could be a potential nonpharmacological remedy for SVaD. This finding could stimulate future investigations on IF's neuroprotective potential across many neurovascular diseases.

Optical spectroscopic imaging for cell therapy and tissue engineering.

Cell-based therapies hold great potential to treat a wide range of human diseases, yet the mechanisms responsible for cell migration and homing are not fully understood. Emerging molecular imaging technology enables in vivo tracking of transplanted cells and their therapeutic efficacy, which together will improve the clinical outcome of cell-based therapy. Particularly, optical imaging provides highly sensitive, safe (non-radioactive), cost-effective, and fast solutions for real-time cellular trafficking compared to other conventional molecular imaging modalities. This review provides a comprehensive overview of current advances in optical imaging for cell-based therapy and tissue engineering. We discuss different types of fluorescent probes and their labeling methods with a special focus on cardiovascular disease, cancer immunotherapy, and tissue regeneration. In addition, advantages and limitations of optical imaging-based cell tracking strategies along with the future perspectives to translate this imaging technique for a clinical realm are discussed.