Objective-The cognitive features and treatment of autism spectrum disorder (ASD) have been the subject of much debate in recent years. Therapeutic approaches to date have focused on skills acquisition, support tailored to the characteristics of ASD, and interventions in social cognitive functioning; there have been few reports describing interventions aimed at neurocognitive dysfunction. In this study we focus on impairment of executive functioning in ASD patients and investigate improvements in executive functioning and their generalization to social functioning. Method-The intervention adopted for this study was cognitive remediation therapy using the frontal/executive program (FEP). To investigate the effectiveness of FEP, 15 subjects who consented to participate in the study were randomly assigned to an intervention group or control group. FEP was administered to the intervention group for about 6 months. Both groups were evaluated using the same scales: BACS-J, WCST and CPT for cognitive assessment, SCoRS-J, GAF and LASMI for social functioning, and GSE for self-efficacy. Results-Both groups had lower scores for cognitive functioning than normal individuals at baseline. After completion of FEP, the intervention group showed improved performance on BACS-J for overall score, digit sequencing, verbal fluency, and Tower of London tasks. Improvements were also seen on SCoRS-J and LASMI scales of 4 social functioning. Conclusions-This was the first study to use FEP to focus on neurocognitive dysfunction in ASD patients. FEP is effective in improving impaired executive functioning in ASD patients and may also lead to improvements in some aspects of social functioning.

Neuropsychiatric manifestations targeting the central, peripheral, and autonomic nervous system are common in systemic lupus erythematosus (SLE); collectively, these symptoms are termed neuropsychiatric SLE (NPSLE). Among a wide variety of neuropsychiatric symptoms, depression is observed in about 24-39% of SLE patients. Several cytokines and chemokines have been identified as biomarkers or therapeutic targets of NPSLE; in particular, the levels of type 1 interferons, TNFs, and IL-6 are elevated in SLE patient’s cerebrospinal fluid (CSF), and these factors contribute to the pathology of depression. Here, we show that senescent neural cells accumulate in the hippocampal cornu ammonis 3 (CA3) region in MRL/lpr SLE model mice with depressive behavior. Furthermore, oral administration of fisetin, a senolytic drug, reduced the number of senescent neural cells and reduced depressive behavior in the MRL/lpr mice. In addition, transcription of several senescence and senescence-associated secretory phenotype (SASP) factors in the hippocampal region also decreased after fisetin treatment in the MRL/lpr mice. These results indicate that the accumulation of senescent neural cells in the hippocampus plays a role in NPSLE pathogenesis, and therapies targeting senescent cells may represent a candidate approach to treat NPSLE.

Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence–associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes.