HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization- activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety- like behavior in stress-naı ̈ve mice, whereas VTA HCN2 overexpression largely prevented CMS- induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors

Effects of rest interval and training intensity on jumping performance: a systematic review and meta-analysis investigating post-activation performance enhancement

Background: There is no clear agreement regarding the ideal rest interval and training intensity to optimize post-activation performance enhancement (PAPE) after barbell squat (BS). Therefore, the aim of this study was to investigate the effects of rest interval and training intensity on jumping performance due to PAPE.Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: (1) eligible studies should be randomized controlled trials; (2) eligible studies should investigate the acute effect of barbell squat-induced PAPE on jump performance; (3) eligible studies should use countermovement jump, squat jump, or vertical jump as the outcome measure.Results: From 2518 search records initially identified, 19 studies were eligible for meta-analysis. Our meta-analysis results showed that BS had no significant effect on improving jumping performance due to PAPE (Cohen’s d = 0.09, p = 0.08). Subgroup analysis showed that rest interval between 0–1 min was detrimental to jumping performance (Cohen’s d = −0.33, p < 0.01), while rest intervals between 4–7 min (Cohen’s d = 0.31, p < 0.01) and 8-9 min (Cohen’s d = 0.26, p = 0.02) provided favorable jumping performance outcomes. In addition, low-intensity and moderate-intensity BS had no significant effect on jump performance, while high-intensity BS showed results consistent with rest interval.Conclusion: Our study indicated that both low-intensity and moderate-intensity BS failed to induce PAPE, and it is recommended that future studies use high-intensity BS to induce PAPE. A rest interval of 4–9 min had a beneficial impact on jump height, and an interval range of 4–7 min seems to be the best rest interval between conditioning activity and jumping performance

Angiotensin-Converting Enzyme Gene D/I Polymorphism in Relation to Endothelial Function and Endothelial-Released Factors in Chinese Women

Many studies have investigated the relationship between angiotensin-converting enzyme (ACE) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect toACED/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22-75 years) were enrolled and divided into pre-menopause group and post-menopause group. AfterACED/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies ofACED/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD (P= 0.032), and age-dependent in both genotypes (DD,P= 0.0472; DI/II,P< 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II (P< 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II (P= 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO,P= 0.032; ET-1,P= 0.017; Ang II,P= 0.002), but only with Ang II in women of DI/II (P= 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD (P= 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease

Aerobic exercise regulates Rho/cofilin pathways to rescue synaptic loss in aged rats.

PURPOSE:The role of exercise to prevent or reverse aging-induced cognitive decline has been widely reported. This neuroprotection is associated with changes in the synaptic structure plasticity. However, the mechanisms of exercise-induced synaptic plasticity in the aging brain are still unclear. Thus, the aim of the present study is to investigate the aging-related alterations of Rho-GTPase and the modulatory influences of exercise training. METHODS:Young and old rats were used in this study. Old rats were subjected to different schedules of aerobic exercise (12 m/min, 60 min/d, 3d/w or 5d/w) or kept sedentary for 12 w. After 12 w of aerobic exercise, the synapse density in the cortex and hippocampus was detected with immunofluorescent staining using synaptophysin as a marker. The total protein levels of RhoA, Rac1, Cdc42 and cofilin in the cortex and hippocampus were detected with Western Blot. The activities of RhoA, Rac1 and Cdc42 were determined using a pull down assay. RESULTS:We found that synapse loss occurred in aging rats. However, the change of expression and activity of RhoA, Rac1 and Cdc42 was different in the cortex and hippocampus. In the cortex, the expression and activity of Rac1 and Cdc42 was greatly increased with aging, whereas there were no changes in the expression and activity of RhoA. In the hippocampus, the expression and activity of Rac1 and Cdc42 was greatly decreased and there were no changes in the expression and activity of RhoA. As a major downstream substrate of the Rho GTPase family, the increased expression of cofilin was only observed in the cortex. High frequency exercise ameliorated all aging-related changes in the cortex and hippocampus. CONCLUSIONS:These data suggest that aerobic exercise reverses synapse loss in the cortex and hippocampus in aging rats, which might be related to the regulation of Rho GTPases

Treadmill Exercise Prevents Decline in Spatial Learning and Memory in 3×Tg-AD Mice through Enhancement of Structural Synaptic Plasticity of the Hippocampus and Prefrontal Cortex

Alzheimer’s disease (AD) is characterized by deficits in learning and memory. A pathological feature of AD is the alterations in the number and size of synapses, axon length, dendritic complexity, and dendritic spine numbers in the hippocampus and prefrontal cortex. Treadmill exercise can enhance synaptic plasticity in mouse or rat models of stroke, ischemia, and dementia. The aim of this study was to examine the effects of treadmill exercise on learning and memory, and structural synaptic plasticity in 3×Tg-AD mice, a mouse model of AD. Here, we show that 12 weeks treadmill exercise beginning in three-month-old mice improves spatial working memory in six-month-old 3×Tg-AD mice, while non-exercise six-month-old 3×Tg-AD mice exhibited impaired spatial working memory. To investigate potential mechanisms for the treadmill exercise-induced improvement of spatial learning and memory, we examined structural synaptic plasticity in the hippocampus and prefrontal cortex of six-month-old 3×Tg-AD mice that had undergone 12 weeks of treadmill exercise. We found that treadmill exercise led to increases in synapse numbers, synaptic structural parameters, the expression of synaptophysin (Syn, a presynaptic marker), the axon length, dendritic complexity, and the number of dendritic spines in 3×Tg-AD mice and restored these parameters to similar levels of non-Tg control mice without treadmill exercise. In addition, treadmill exercise also improved these parameters in non-Tg control mice. Strengthening structural synaptic plasticity may represent a potential mechanism by which treadmill exercise prevents decline in spatial learning and memory and synapse loss in 3×Tg-AD mice

Listening to Self-Selected Music during Warm-Up Improves Anaerobic Performance through Enhancement of the Excitability of the Cerebral Cortex

The study investigated the effects of listening to self-selected music during a warm-up on brain wave synchronization/desynchronization and Wingate test performance. Seventeen healthy young men were required to complete a 10 min warm-up session with or without music intervention, followed by an electroencephalogram (EEG) or Wingate test, respectively. The ratings of perceived exertion (RPE) and heart rate (HR) were recorded immediately after the Wingate test. Compared with no music intervention, listening to self-selected music during a warm-up significantly increased peak power and mean power in the Wingate test (p p p p p p p > 0.05). This study demonstrated that listening to self-selected music during a warm-up enhances cortical excitability by upregulating the α and β energy percentages and downregulating the δ energy percentage, which may represent a potential mechanism by which listening to self-selected music during a warm-up improves anaerobic performance in healthy young men

Exercise decreased the increased expression of cofilin in the cortex during aging.

<p><b>(A-B)</b> Immunoreactive bands corresponding to cofilin and GAPDH in the cortex (A) and hippocampus (B). <b>(C-D)</b> Summarized data of cofilin protein levels (as a ratio to GAPDH) in the cortex (C) and hippocampus (D). Values are mean and standard error of the mean, n = 5 in each group. ** P< 0.01 vs. YC, ^## P< 0.01 vs. O-SED.</p

Exercise reverses the synapse loss during aging.

<p><b>(A-B)</b> Representative positive immunofluorescence staining of synaptophysin in the cortex (A) and hippocampus (B) in four groups. <b>(C-D)</b> Summary of the mean fluorescence density in the cortex (C) and hippocampus (D) in four groups. Values are mean and standard error of the mean, n = 5 in each group. ** P< 0.01 vs. YC, ^#P< 0.05 vs. O-SED, ^& P< 0.05 vs. O-LEX. Bar = 100 μm.</p