Considerable effects of lateralization and aging in intracortical excitation and inhibition

IntroductionFindings based on the use of transcranial magnetic stimulation and electromyography (TMS-EMG) to determine the effects of motor lateralization and aging on intracortical excitation and inhibition in the primary motor cortex (M1) are inconsistent in the literature. TMS and electroencephalography (TMS-EEG) measures the excitability of excitatory and inhibitory circuits in the brain cortex without contamination from the spine and muscles. This study aimed to investigate the effects of motor lateralization (dominant and non-dominant hemispheres) and aging (young and older) and their interaction effects on intracortical excitation and inhibition within the M1 in healthy adults, measured using TMS-EMG and TMS-EEG.MethodsThis study included 21 young (mean age = 28.1 ± 3.2 years) and 21 older healthy adults (mean age = 62.8 ± 4.2 years). A battery of TMS-EMG measurements and single-pulse TMS-EEG were recorded for the bilateral M1.ResultsTwo-way repeated-measures analysis of variance was used to investigate lateralization and aging and the lateralization-by-aging interaction effect on neurophysiological outcomes. The non-dominant M1 presented a longer cortical silent period and larger amplitudes of P60, N100, and P180. Corticospinal excitability in older participants was significantly reduced, as supported by a larger resting motor threshold and lower motor-evoked potential amplitudes. N100 amplitudes were significantly reduced in older participants, and the N100 and P180 latencies were significantly later than those in young participants. There was no significant lateralization-by-aging interaction effect in any outcome.ConclusionLateralization and aging have independent and significant effects on intracortical excitation and inhibition in healthy adults. The functional decline of excitatory and inhibitory circuits in the M1 is associated with aging

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Neural correlates of fine motor grasping skills: Longitudinal insights into motor cortex activation using fNIRS

Abstract Background Motor learning is essential for performing specific tasks and progresses through distinct stages, including the rapid learning phase (initial skill acquisition), the consolidation phase (skill refinement), and the stable performance phase (skill mastery and maintenance). Understanding the cortical activation dynamics during these stages can guide targeted rehabilitation interventions. Methods In this longitudinal randomized controlled trial, functional near‐infrared spectroscopy was used to explore the temporal dynamics of cortical activation in hand‐related motor learning. Thirty‐one healthy right‐handed individuals were randomly assigned to perform either easy or intricate motor tasks with their non‐dominant hand over 10 days. We conducted 10 monitoring sessions to track cortical activation in the right hemisphere (according to lateralization principles, the primary hemisphere for motor control) and evaluated motor proficiency concurrently. Results The study delineated three stages of nondominant hand motor learning: rapid learning (days 1 and 2), consolidation (days 3–7), and stable performance (days 8–10). There was a power‐law enhancement of motor skills correlated with learning progression. Sustained activation was observed in the supplementary motor area (SMA) and parietal lobe (PL), whereas activation in the right primary motor cortex (M1R) and dorsolateral prefrontal cortex (PFCR) decreased. These cortical activation patterns exhibited a high correlation with the augmentation of motor proficiency. Conclusions The findings suggest that early rehabilitation interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), could be optimally directed at M1 and PFC in the initial stages. In contrast, SMA and PL can be targeted throughout the motor learning process. This research illuminates the path for developing tailored motor rehabilitation interventions based on specific stages of motor learning. NEW and NOTEWORTHY In an innovative approach, our study uniquely combines a longitudinal design with the robustness of generalized estimating equations (GEEs). With the synergy of functional near‐infrared spectroscopy (fNIRS) and the Minnesota Manual Dexterity Test (MMDT) paradigm, we precisely trace the evolution of neural resources during complex, real‐world fine‐motor task learning. Centering on right‐handed participants using their nondominant hand magnifies the intricacies of right hemisphere spatial motor processing. We unravel the brain's dynamic response throughout motor learning stages and its potent link to motor skill enhancement. Significantly, our data point toward the early‐phase rehabilitation potential of TMS and transcranial direct current stimulation on the M1 and PFC regions. Concurrently, SMA and PL appear poised to benefit from ongoing interventions during the entire learning curve. Our findings carve a path for refined motor rehabilitation strategies, underscoring the importance of timely noninvasive brain stimulation treatments

Upregulation of protein phosphatase 2A and NR3A-pleiotropic effect of simvastatin on ischemic stroke rats.

Ca(2+) influxes are regulated by the functional state of N-methyl-D-aspartate receptors (NMDARs). Dephosphorylation of NMDARs subunits decreases Ca(2+) influxes. NR3, a novel subunit of NMDARs, also decreases Ca(2+) influxes by forming new NMDARs with NR1 and NR2. It is meaningful to uncover whether protein phosphatase 2A (PP2A) and NR3A play a role in the protective effect of Simvastatin on ischemic stroke. In the present study, the Sprague-Dawley rats were pretreated with Simvastatin for 7 days before middle cerebral artery occlusion was performed to mimic ischemic stroke. The results showed that Simvastatin decreased brain ischemic infarct area significantly while increasing the expression levels of PP2A and NR3A, thus dephosphorylating the serine sites of NR1 (ser896 and ser897) along with increased enzymatic activities of PP2A. The protein levels of NR3A decreased as the enzymatic activities of PP2A were inhibited by okadaic acid. The results indicated that Simvastatin could protect the cerebrum from ischemic injury through a signaling mechanism involving elevated levels of PP2A and NR3A, and that PP2A might involve in the regulatory mechanism of NR3A expression

Flavanones from Sedum sarmentosum Bunge Alleviate CCl4-Induced Liver Fibrosis in Rats by Targeting TGF-β1/TβR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition

Objective. The aim of the study is to evaluate the therapeutic effects of flavanones from Sedum sarmentosum Bunge (FSSB) on CCl4-induced liver fibrosis in rats and the underlying mechanisms of action. Methods. An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl4 (40% v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was intragastrically administered once per day consecutively for five weeks. Results. Our results showed that FSSB significantly attenuated CCl4-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), and laminin (LN) level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-β1, TGF-β1 receptors I and II (TβRI and TβRII), Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin. Conclusions. The results suggest that FSSB alleviated CCl4-induced liver fibrosis probably through inhibition of TGF-β/TβR/Smad pathway in turn inhibiting epithelial mesenchymal transition

Effect of Drought on Agronomic Traits of Rice and Wheat: A Meta-Analysis

Drought has been one of the most important limiting factors for crop production, which deleteriously affects food security worldwide. The main objective of the present study was to quantitatively assess the effect of drought on the agronomic traits (e.g., plant height, biomass, yield, and yield components) of rice and wheat in combination with several moderators (e.g., drought stress intensity, rooting environment, and growth stage) using a meta-analysis study. The database was created from 55 published studies on rice and 60 published studies on wheat. The results demonstrated that drought decreased the agronomic traits differently between rice and wheat among varying growth stages. Wheat and rice yields decreased by 27.5% and 25.4%, respectively. Wheat grown in pots showed greater decreases in agronomic traits than those grown in the field. Rice showed opposite growing patterns when compared to wheat in rooting environments. The effect of drought on rice increased with plant growth and drought had larger detrimental influences during the reproductive phase (e.g., blooming stage, filling stage, and maturity). However, an exception was found in wheat, which had similar decreased performance during the complete growth cycle. Based on these results, future droughts could produce lower yields of rice and wheat when compared to the current drought

The effect of orexin-A on cardiac dysfunction mediated by NADPH oxidase-derived superoxide anion in ventrolateral medulla.

Hypocretin/orexin-producing neurons, located in the perifornical region of the lateral hypothalamus area (LHA) and projecting to the brain sites of rostral ventrolateral medulla (RVLM), involve in the increase of sympathetic activity, thereby regulating cardiovascular function. The current study was designed to test the hypothesis that the central orexin-A (OXA) could be involved in the cardiovascular dysfunction of acute myocardial infarction (AMI) by releasing NAD(P)H oxidase-derived superoxide anion (O2 (-)) generation in RVLM, AMI rat model established by ligating the left anterior descending (LAD) coronary artery to induce manifestation of cardiac dysfunction, monitored by the indicators as heart rate (HR), heart rate variability (HRV), mean arterial pressure (MAP) and left intraventricular pressure. The results showed that the expressions of OXA in LHA and orexin 1 receptor (OX1R) increased in RVLM of AMI rats. The double immunofluorescent staining indicated that OX1R positive cells and NAD(P)H oxidative subunit gp91phox or p47phox-immunoreactive (IR) cells were co-localized in RVLM. Microinjection of OXA into the cerebral ventricle significantly increased O2 (-) production and mRNA expression of NAD(P)H oxidase subunits when compared with aCSF-treated ones. Exogenous OXA administration in RVLM produced pressor and tachycardiac effects. Furthermore, the antagonist of OX1R and OX2R (SB-408124 and TCS OX2 29, respectively) or apocynin (APO), an inhibitor of NAD(P)H oxidase, partly abolished those cardiovascular responses of OXA. HRV power spectral analysis showed that exogenous OXA led to decreased HF component of HRV and increased LF/HF ratio in comparison with aCSF, which suggested that OXA might be related to sympathovagal imbalance. As indicated by the results, OXA might participate in the central regulation of cardiovascular activities by disturbing the sympathovagal balance in AMI, which could be explained by the possibility that OXR and NAD(P)H-derived O2 (-) in RVLM mediates OXA-induced cardiovascular responses

The effects of angiotensin II and angiotensin-(1-7) in the rostral ventrolateral medulla of rats on stress-induced hypertension.

We have shown that angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1-7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1-7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and γ-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT₁ receptor (AT₁R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT₂ receptor (AT₂R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1-7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT₁R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT₂R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT₁R, not Ang-(1-7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release

Simvastatin increased mRNA expression and protein levels of NR3A of MCAO rats in hippocampus CA1 region. A:

<p>NR3A mRNA levels analyzed by quantitative real-time PCR; values expressed as means ± SEM of 5 rats; **<i>P</i><0.01, MCAO <i>vs</i>. sham group, vehicle+MCAO <i>vs</i>. sham group; ##<i>P</i><0.01, sim+MCAO <i>vs</i>. MCAO group; &&<i>P</i><0.01, sim+MCAO <i>vs</i>. vehicle+MCAO group. <b>B:</b> representative blots showing the levels of NR3A in each group. <b>C:</b> semiquantitative analysis of the levels of NR3A; values expressed as means ± SEM of 5 rats; **<i>P</i><0.01, MCAO <i>vs</i>. sham group; vehicle+MCAO <i>vs</i>. sham group; ##<i>P</i><0.01, sim+MCAO <i>vs</i>. MCAO group; &&<i>P</i><0.01, sim+MCAO <i>vs</i>. vehicle+MCAO group. Sim, Simvastatin.</p