Background Cardiac ischemic/reperfusion (I/R) injury leads to brain damage. A new antihyperlipidemic drug is aimed at inhibiting PCSK 9 (proprotein convertase subtilisin/kexin type 9), a molecule first identified in a neuronal apoptosis paradigm. Thus, the PCSK 9 inhibitor ( PCSK 9i) may play a role in neuronal recovery following cardiac I/R insults. We hypothesize that PCSK 9i attenuates brain damage caused by cardiac I/R via diminishing microglial/astrocytic hyperactivation, β‐amyloid aggregation, and loss of dendritic spine. Methods and Results Adult male rats were divided into 7 groups: (1) control (n=4); (2) PCSK 9i without cardiac I/R (n=4); (3) sham (n=4); and cardiac I/R (n=40). Cardiac I/R rats were divided into 4 subgroups (n=10/subgroup): (1) vehicle; (2) PCSK 9i (10 μg/kg, IV) before ischemia; (3) PCSK 9i during ischemia; and (4) PCSK 9i at the onset of reperfusion. At the end of cardiac I/R protocol, brains were removed to determine microglial and astrocytic activities, β‐amyloid aggravation, and dendritic spine density. The cardiac I/R led to the activation of the brain's innate immunity resulting in increasing Iba1 + microglia, GFAP + astrocytes, and CD 11b + / CD 45 +high cell numbers. However, CD 11b + / CD 45 +low cell numbers were decreased following cardiac I/R. In addition, cardiac I/R led to reduced dendritic spine density, and increased β‐amyloid aggregation. Only the administration of PCSK 9i before ischemia effectively attenuated these deleterious effects on the brain following cardiac I/R. PCSK 9i administration under the physiologic condition did not affect the aforementioned parameters. Conclusions Cardiac I/R injury activated microglial activity in the brain, leading to brain damage. Only the pretreatment with PCSK 9i prevented dendritic spine loss via reduction of microglial activation and Aβ aggregation.

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Background: Attention deficit hyperactivity disorder (ADHD) is associated with depression among college students, while perceived social support is also associated with depression, especially among young adults. This study aimed to examine to what extent perceived social support mediated the relationship between ADHD symptoms and depressive symptoms. Methods: In total, 124 first year medical students completed the Adult ADHD Self-Report Scale Screener (ASRS), the Patient Health questionnaire-9 and the revised Thai Multidimensional scale of perceived social support reflecting ADHD symptoms, depressive symptoms, and perceive social support, i.e., family members, friends and other significant people, respectively. Structural equation modeling was used to investigate the hypothesized mediation model. Results: ADHD symptoms exhibited a significant indirect effect on depressive symptoms via perceived social support. ADHD symptoms initially had a direct effect on depression; thereafter, it reduced to a non-significance effect after perceived social support was added. The total variance explained by this model was 35.2%. The mediation model with family support as a mediator showed the highest effect size. Conclusions: The study highlighted the importance of perceived social support, particularly family support, on depressive symptoms among young medical students experiencing ADHD symptoms. The model suggests promising relationships for further research on ADHD-related depression and potential treatment in the future.

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.