Hyperbaric oxygen therapy restores cognitive function and hippocampal pathologies in both aging and aging-obese rats.

The population of obese-elderly has increased prominently around the world. Both aging and obesity are major factors of neurodegeneration. The present study hypothesizes that HBOT attenuates metabolic disturbance, cognitive decline, hippocampal pathologies in aging and aging-obese model. Sixty Wistar rats were separated into 2 groups to receive normal-diet (ND) or high-fat diet (HFD) for 22 weeks. At week 13, ND rats were divided into two subgroups to receive vehicle (0.9 % NSS, s.c) or d-gal (150 mg/kg/d, s.c) for total 10 weeks. HFD rats were injected only d-gal (150 mg/kg/d, s.c; HFDD) for total 10 weeks. At week 20, rats in each subgroup were given sham-treatment (1ATA, 80 L/min, 80 min/day), or HBOT (2ATA, pure O2, 250 L/min, 80 min/day) for 14 days. Novel object location test, metabolic parameters, and hippocampal pathologies were determined after HBOT. d-gal induced insulin resistance, increased oxidative stress, autophagy impairment, microglial hyperactivation, apoptosis, synaptic dysplasticity which resulted in cognitive impairment. d-gal-treated HFD-fed rats had the highest levels of oxidative stress, apoptosis, dendritic spine loss. HBOT attenuated insulin resistance, cognitive impairment, hippocampal aging and pathologies in both models. These findings suggest that HBOT restored insulin sensitivity, hippocampal functions, cognition in aging and aging-obese models.

Tai Chi Improves Cognition and Plasma BDNF in Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial.

BACKGROUND: Effects of Tai Chi (TC) on specific cognitive function and mechanisms by which TC may improve cognition in older adults with amnestic mild cognitive impairment (a-MCI) remain unknown. OBJECTIVE: To examine the effects of TC on cognitive functions and plasma biomarkers (brain-derived neurotrophic factor [BDNF], tumor necrosis factor-α [TNF-α], and interleukin-10 [IL-10]) in a-MCI. METHODS: A total of 66 older adults with a-MCI (mean age = 67.9 years) were randomized to either a TC (n = 33) or a control group (n = 33). Participants in the TC group learned TC with a certified instructor and then practiced at home for 50 min/session, 3 times/wk for 6 months. The control group received educational material that covered information related to cognition. The primary outcome was cognitive performance, including Logical Memory (LM) delayed recall, Block Design, Digit Span, and Trail Making Test B minus A (TMT B-A). The secondary outcomes were plasma biomarkers, including BDNF, TNF-α, and IL-10. RESULTS: At the end of the trial, performance on the LM and TMT B-A was significantly better in the TC group compared with the control group after adjusting for age, gender, and education ( P < .05). Plasma BDNF level was significantly increased for the TC group, whereas the other outcome measures were similar between the 2 groups after adjusting for age and gender ( P < .05). CONCLUSIONS: TC training significantly improved memory and the mental switching component of executive function in older adults with a-MCI, possibly via an upregulation of BDNF.

Dual T-type and L-type calcium channel blocker exerts beneficial effects in attenuating cardiovascular dysfunction in iron-overloaded thalassaemic mice.

NEW FINDINGS: What is the central question of this study? Head-to-head comparison of the therapeutic efficacy among commercial iron chelators and a dual T- (TTCC) and L-type calcium channel (LTCC) blocker on cardiac function, mitochondrial function and the protein expression of cardiac iron transporters in thalassaemic mice in iron-overloaded conditions has not been assessed. What is the main finding and its importance? The dual TTCC and LTCC blocker efonidipine could provide broad beneficial effects in the heart, liver, plasma and mitochondria in both wild-type and thalassaemic mice in iron-overloaded conditions. Its beneficial effects are of the same degree as the three commercial iron chelators currently used clinically. It is possible that efonidipine could be an alternative choice in patients unable to take iron chelators for the treatment of iron-overload conditions. Iron chelation therapy is a standard treatment in thalassaemia patients; however, its poor cardioprotective efficacy and serious side-effects are a cause for concern. Previous studies have shown that treatment with L-type calcium channel (LTCC) blockers or dual T-type calcium channel (TTCC) and LTCC blockers decreases cardiac iron and improves cardiac dysfunction in an iron-overloaded rodent model. Currently, the head-to-head comparison of therapeutic efficacy among commercial iron chelators, a dual TTCC and LTCC blocker and an LTCC blocker on cardiac function, mitochondrial function and the protein expression of cardiac iron transporters in thalassaemic mice in an iron-overloaded state has never been investigated. An iron-overloaded state was induced in ß-thalassaemic and wild-type mice. Cardiac iron overload was induced to a greater extent than in a previous study by feeding the mice with an iron-enriched diet for 4 months. Then, an LTCC blocker (amlodipine) or a dual TTCC and LTCC blocker (efonidipine) or one of the commercial iron chelators (deferoxamine, deferasirox or deferiprone) was administered for 1 month with continuous iron feeding. All treatments reduced cardiac iron deposition and improved mitochondrial and cardiac dysfunction in both types of mice. Only efonidipine and the iron chelators reduced liver iron accumulation, liver malondialdehyde and plasma malondialdehyde in these mice. Although all pharmacological interventions reduced cardiac iron deposition, they did not alter the protein expression levels of cardiac iron transporter. These findings indicated that efonidipine provided all benefits to the same degree as the three commercial iron chelators. These findings indicate that a dual TTCC and LTCC blocker could be beneficial for treatment of an iron-overloaded state.

T-type calcium channel blockade improves survival and cardiovascular function in thalassemic mice.

OBJECTIVES: Iron-overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. However, the precise mechanisms of iron entry and sequestration in the heart are still unclear. Our previous study showed that Fe(2+) uptake in thalassemic cardiomyocytes are mainly mediated by T-type calcium channels (TTCC). Nevertheless, the role of TTCC as well as other transporters such as divalent metal transporter1 (DMT1) and L-type calcium channels (LTCC) as possible portals for iron entry into the heart in in vivo thalassemic mice under an iron-overload condition has not been investigated. METHODS: An iron-overload condition was induced in genetically altered ß-thalassemic mice and adult wild-type mice by feeding them with an iron diet (0.2% ferrocene w/w) for 3 months. Then, blockers for LTCC (verapamil and nifedipine), TTCC (efonidipine), and DMT1 (ebselen) as well as iron chelator desferoxamine (DFO) were given for 1 month with continuous iron feeding. RESULTS: Treatment with LTCC, TTCC, DMT1 blockers, and DFO reduced cardiac iron deposit, cardiac malondialdehyde (MDA), plasma non-transferrin-bound iron, and improved heart rate variability and left ventricular (LV) function in thalassemic mice with iron overload. Only TTCC and DMT1 blockers and DFO reduced liver iron accumulation, liver MDA, plasma MDA, and decreased mortality rate in iron-overloaded thalassemic mice. CONCLUSIONS: DMT1, LTCC, and TTCC played important roles for iron entry in the thalassemic heart under an iron-overloaded condition. Unlike LTCC blocker, TTCC blocker provided all benefits including attenuating iron deposit in both the heart and liver, reduced oxidative stress, and decreased mortality in iron-overloaded mice.