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Health Promotion International Aug 2023Based on the health action process approach (HAPA) this study examined whether changes in social cognition constructs could predict change in physical activity and fruit...
Based on the health action process approach (HAPA) this study examined whether changes in social cognition constructs could predict change in physical activity and fruit and vegetable intake for adult participants in My health for life, an Australian health promotion behaviour change program. Variance-based structural equation modelling was used to analyse data obtained from Australian adult program participants (n = 167) at baseline (T1), week 14 (T2), week 26 (T2), and 6-month post-program (T4). Change scores were calculated for the social cognition constructs and behaviour. Changes in action self-efficacy and outcome expectancies positively predicted changes in intentions. Action self-efficacy changes also predicted changes in maintenance self-efficacy which, in turn, mediated the effect of action self-efficacy on recovery self-efficacy and planning. Planning was predicted by changes in intentions and maintenance self-efficacy. Findings support the use of the HAPA model in designing complex health behaviour change interventions to achieve sustained behaviour change.
Topics: Humans; Adult; Fruit; Australia; Vegetables; Exercise; Intention
PubMed: 37647521
DOI: 10.1093/heapro/daad095 -
Brain Communications 2024The transformation from perception to action requires a set of neuronal decisions about the nature of the percept, identification and selection of response options and...
The transformation from perception to action requires a set of neuronal decisions about the nature of the percept, identification and selection of response options and execution of the appropriate motor response. The unfolding of such decisions is mediated by distributed representations of the decision variables-evidence and intentions-that are represented through oscillatory activity across the cortex. Here we combine magneto-electroencephalography and linear ballistic accumulator models of decision-making to reveal the impact of Parkinson's disease during the selection and execution of action. We used a visuomotor task in which we independently manipulated uncertainty in sensory and action domains. A generative accumulator model was optimized to single-trial neurophysiological correlates of human behaviour, mapping the cortical oscillatory signatures of decision-making, and relating these to separate processes accumulating sensory evidence and selecting a motor action. We confirmed the role of widespread beta oscillatory activity in shaping the feed-forward cascade of evidence accumulation from resolution of sensory inputs to selection of appropriate responses. By contrasting the spatiotemporal dynamics of evidence accumulation in age-matched healthy controls and people with Parkinson's disease, we identified disruption of the beta-mediated cascade of evidence accumulation as the hallmark of atypical decision-making in Parkinson's disease. In frontal cortical regions, there was inefficient processing and transfer of perceptual information. Our findings emphasize the intimate connection between abnormal visuomotor function and pathological oscillatory activity in neurodegenerative disease. We propose that disruption of the oscillatory mechanisms governing fast and precise information exchanges between the sensory and motor systems contributes to behavioural changes in people with Parkinson's disease.
PubMed: 38505233
DOI: 10.1093/braincomms/fcae065 -
International Journal of Molecular... Jul 2023In angiotensin II (Ang II)-dependent hypertension, Ang II activates angiotensin II type 1 receptors (AT1R) on renal vascular smooth muscle cells, leading to renal... (Review)
Review
In angiotensin II (Ang II)-dependent hypertension, Ang II activates angiotensin II type 1 receptors (AT1R) on renal vascular smooth muscle cells, leading to renal vasoconstriction with eventual glomerular and tubular injury and interstitial inflammation. While afferent arteriolar vasoconstriction is initiated by the increased intrarenal levels of Ang II activating AT1R, the progressive increases in arterial pressure stimulate the paracrine secretion of adenosine triphosphate (ATP), leading to the purinergic P2X receptor (P2XR)-mediated constriction of afferent arterioles. Thus, the afferent arteriolar tone is maintained by two powerful systems eliciting the co-existing activation of P2XR and AT1R. This raises the conundrum of how the AT1R and P2XR can both be responsible for most of the increased renal afferent vascular resistance existing in angiotensin-dependent hypertension. Its resolution implies that AT1R and P2XR share common receptor or post receptor signaling mechanisms which converge to maintain renal vasoconstriction in Ang II-dependent hypertension. In this review, we briefly discuss (1) the regulation of renal afferent arterioles in Ang II-dependent hypertension, (2) the interaction of AT1R and P2XR activation in regulating renal afferent arterioles in a setting of hypertension, (3) mechanisms regulating ATP release and effect of angiotensin II on ATP release, and (4) the possible intracellular pathways involved in AT1R and P2XR interactions. Emerging evidence supports the hypothesis that P2X1R, P2X7R, and AT1R actions converge at receptor or post-receptor signaling pathways but that P2XR exerts a dominant influence abrogating the actions of AT1R on renal afferent arterioles in Ang II-dependent hypertension. This finding raises clinical implications for the design of therapeutic interventions that will prevent the impairment of kidney function and subsequent tissue injury.
Topics: Humans; Adenosine Triphosphate; Angiotensin II; Arterioles; Hypertension; Kidney; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Receptors, Purinergic P2X
PubMed: 37511174
DOI: 10.3390/ijms241411413 -
Journal of Cachexia, Sarcopenia and... Oct 2023The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron...
BACKGROUND
The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown.
METHODS
Hb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1 ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed.
RESULTS
Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63 ± 0.35 vs. 3.93 ± 0.22 s for f/f, P < 0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79 ± 5.74 vs. 79.39 ± 3.77% fully occupied neuromuscular junctions for f/f, P < 0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88 ± 0.13 vs. 1.43 ± 0.48 μm for f/f, P < 0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment.
CONCLUSIONS
Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.
PubMed: 37559423
DOI: 10.1002/jcsm.13308 -
BioRxiv : the Preprint Server For... Oct 2023Methylphenidate (MPH, brand: Ritalin) is a common stimulant used both medically and non-medically. Though typically prescribed for its cognitive effects, MPH also...
Methylphenidate (MPH, brand: Ritalin) is a common stimulant used both medically and non-medically. Though typically prescribed for its cognitive effects, MPH also affects movement. While it is known that MPH noncompetitively blocks the reuptake of catecholamines through inhibition of dopamine and norepinephrine transporters, a critical step in exploring how it affects behavior is to understand how MPH directly affects neural activity. This would establish an electrophysiological mechanism of action for MPH. Since we now have biologically-grounded network-level hypotheses regarding how populations of motor cortical neurons plan and execute movements, there is a unique opportunity to make testable predictions regarding how systemic MPH administration - a pharmacological perturbation - might affect neural activity in motor cortex. To that end, we administered clinically-relevant doses of MPH to Rhesus monkeys as they performed an instructed-delay reaching task. Concomitantly, we measured neural activity from dorsal premotor and primary motor cortex. Consistent with our predictions, we found dose-dependent and significant effects on reaction time, trial-by-trial variability, and movement speed. We confirmed our hypotheses that changes in reaction time and variability were accompanied by previously established population-level changes in motor cortical preparatory activity and the condition-independent signal that precedes movements. We expected changes in speed to be a result of changes in the amplitude of motor cortical dynamics and/or a translation of those dynamics in activity space. Instead, our data are consistent with a mechanism whereby the neuromodulatory effect of MPH is to increase the gain and/or the signal-to-noise of motor cortical dynamics during reaching. Continued work in this domain to better understand the brain-wide electrophysiological mechanism of action of MPH and other psychoactive drugs could facilitate more targeted treatments for a host of cognitive-motor disorders.
PubMed: 37905157
DOI: 10.1101/2023.10.15.562405 -
Cells Sep 2023Integrins were originally identified as receptors for extracellular matrix (ECM) and cell-surface molecules (e.g., VCAM-1 and ICAM-1). Later, we discovered that many... (Review)
Review
Virtual Screening of Protein Data Bank via Docking Simulation Identified the Role of Integrins in Growth Factor Signaling, the Allosteric Activation of Integrins, and P-Selectin as a New Integrin Ligand.
Integrins were originally identified as receptors for extracellular matrix (ECM) and cell-surface molecules (e.g., VCAM-1 and ICAM-1). Later, we discovered that many soluble growth factors/cytokines bind to integrins and play a critical role in growth factor/cytokine signaling (growth factor-integrin crosstalk). We performed a virtual screening of protein data bank (PDB) using docking simulations with the integrin headpiece as a target. We showed that several growth factors (e.g., FGF1 and IGF1) induce a integrin-growth factor-cognate receptor ternary complex on the surface. Growth factor/cytokine mutants defective in integrin binding were defective in signaling functions and act as antagonists of growth factor signaling. Unexpectedly, several growth factor/cytokines activated integrins by binding to the allosteric site (site 2) in the integrin headpiece, which is distinct from the classical ligand (RGD)-binding site (site 1). Since 25-hydroxycholesterol, a major inflammatory mediator, binds to site 2, activates integrins, and induces inflammatory signaling (e.g., IL-6 and TNFα secretion), it has been proposed that site 2 is involved in inflammatory signaling. We showed that several inflammatory factors (CX3CL1, CXCL12, CCL5, sPLA2-IIA, and P-selectin) bind to site 2 and activate integrins. We propose that site 2 is involved in the pro-inflammatory action of these proteins and a potential therapeutic target. It has been well-established that platelet integrin αIIbβ3 is activated by signals from the inside of platelets induced by platelet agonists (inside-out signaling). In addition to the canonical inside-out signaling, we showed that αIIbβ3 can be allosterically activated by inflammatory cytokines/chemokines that are stored in platelet granules (e.g., CCL5, CXCL12) in the absence of inside-out signaling (e.g., soluble integrins in cell-free conditions). Thus, the allosteric activation may be involved in αIIbβ3 activation, platelet aggregation, and thrombosis. Inhibitory chemokine PF4 (CXCL4) binds to site 2 but did not activate integrins, Unexpectedly, we found that PF4/anti-PF4 complex was able to activate integrins, indicating that the anti-PF4 antibody changed the phenotype of PF4 from inhibitory to inflammatory. Since autoantibodies to PF4 are detected in vaccine-induced thrombocytopenic thrombosis (VIPP) and autoimmune diseases (e.g., SLE, and rheumatoid arthritis), we propose that this phenomenon is related to the pathogenesis of these diseases. P-selectin is known to bind exclusively to glycans (e.g., sLex) and involved in cell-cell interaction by binding to PSGL-1 (CD62P glycoprotein ligand-1). Unexpectedly, through docking simulation, we discovered that the P-selectin C-type lectin domain functions as an integrin ligand. It is interesting that no one has studied whether P-selectin binds to integrins in the last few decades. The integrin-binding site and glycan-binding site were close but distinct. Also, P-selectin lectin domain bound to site 2 and allosterically activated integrins.
Topics: P-Selectin; Allosteric Regulation; Ligands; Cell Communication; Intercellular Signaling Peptides and Proteins; Immunologic Factors; Cytokines; Platelet Glycoprotein GPIIb-IIIa Complex
PubMed: 37759488
DOI: 10.3390/cells12182265 -
Nutrients Jul 2023Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative,... (Review)
Review
Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative, neovascular), which may cause legal blindness and sight loss. Currently, there is not any effective treatment for dry AMD. Meanwhile, repeated intravitreal injections with antibodies effective against vascular endothelial growth factor A (VEGFA) slow down wet AMD progression but are not free from complications. (-)-Epigallocatechin-3-gallate (EGCG) is an active compound of green tea, which exerts many beneficial effects in the retinal pigment epithelium and the neural retina. It has been reported to downregulate the gene by suppressing its activators. The inhibition of mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3) may lie behind the antiangiogenic action of EGCG mediated by VEGFA. EGCG exerts protective effects against UV-induced damage to retinal cells and improves dysfunctional autophagy. EGCG may also interact with the mechanistic target rapamycin (MTOR) and unc-51-like autophagy activating kinase (ULK1) to modulate the interplay between autophagy and apoptosis. Several other studies report beneficial effects of EGCG on the retina that may be related to wet AMD. Therefore, controlled clinical trials are needed to verify whether diet supplementation with EGCG or green tea consumption may improve the results of anti-VEGFA therapy in wet AMD.
Topics: Humans; Vascular Endothelial Growth Factor A; Tea; Retina; Macular Degeneration
PubMed: 37571296
DOI: 10.3390/nu15153358 -
The Journal of Neuroscience : the... Nov 2023Motor actions, such as reaching or grasping, can be decoded from fMRI activity of early visual cortex (EVC) in sighted humans. This effect can depend on vision or visual...
Motor actions, such as reaching or grasping, can be decoded from fMRI activity of early visual cortex (EVC) in sighted humans. This effect can depend on vision or visual imagery, or alternatively, could be driven by mechanisms independent of visual experience. Here, we show that the actions of reaching in different directions can be reliably decoded from fMRI activity of EVC in congenitally blind humans (both sexes). Thus, neither visual experience nor visual imagery is necessary for EVC to represent action-related information. We also demonstrate that, within EVC of blind humans, the accuracy of reach direction decoding is highest in areas typically representing foveal vision and gradually decreases in areas typically representing peripheral vision. We propose that this might indicate the existence of a predictive, hard-wired mechanism of aligning action and visual spaces. This mechanism might send action-related information primarily to the high-resolution foveal visual areas, which are critical for guiding and online correction of motor actions. Finally, we show that, beyond EVC, the decoding of reach direction in blind humans is most accurate in dorsal stream areas known to be critical for visuo-spatial and visuo-motor integration in the sighted. Thus, these areas can develop space and action representations even in the lifelong absence of vision. Overall, our findings in congenitally blind humans match previous research on the action system in the sighted, and suggest that the development of action representations in the human brain might be largely independent of visual experience. Early visual cortex (EVC) was traditionally thought to process only visual signals from the retina. Recent studies proved this account incomplete, and showed EVC involvement in many activities not directly related to incoming visual information, such as memory, sound, or action processing. Is EVC involved in these activities because of visual imagery? Here, we show robust reach direction representation in EVC of humans born blind. This demonstrates that EVC can represent actions independently of vision and visual imagery. Beyond EVC, we found that reach direction representation in blind humans is strongest in dorsal brain areas, critical for action processing in the sighted. This suggests that the development of action representations in the human brain is largely independent of visual experience.
Topics: Male; Female; Humans; Visual Perception; Brain; Visual Cortex; Brain Mapping; Blindness; Magnetic Resonance Imaging
PubMed: 37783506
DOI: 10.1523/JNEUROSCI.0376-23.2023 -
Journal of Translational Medicine Oct 2023Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a...
BACKGROUND
Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear.
AIMS
In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments.
METHODS
SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR.
RESULTS
In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways.
CONCLUSIONS
In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.
Topics: Animals; Male; Rats; Docosahexaenoic Acids; Drugs, Chinese Herbal; Glycopeptides; Lycium; Neuroinflammatory Diseases; NF-kappa B; Pyroptosis; Spinal Cord Injuries
PubMed: 37907930
DOI: 10.1186/s12967-023-04648-9 -
Life Sciences Feb 2024Physical exercise has been widely recognized for its positive effects on health and well-being. Recently, the impact of exercise on the nervous system has gained... (Review)
Review
AIMS
Physical exercise has been widely recognized for its positive effects on health and well-being. Recently, the impact of exercise on the nervous system has gained attention, with evidence indicating improvements in attention, memory, neurogenesis, and the release of "happiness hormones." One potential mediator of these benefits is Irisin, a myokine induced by exercise that can cross the blood-brain barrier, reduce neuroinflammation, and counteract neurodegeneration. The objective of this study is to conduct a systematic review of animal trials to summarize the neuroprotective effects of Irisin injection in mitigating neuroinflammation and neurodegeneration.
MATERIALS AND METHODS
Two independent reviewers screened three databases (PubMed, Embase, and Google Scholar) in November 2022. Animal studies assessing the neuroprotective effects of Irisin in mitigating neuroinflammation or counteracting neurodegeneration were included. The methodological quality of the included studies was assessed using SYRCLE's Risk of Bias tool.
KEY FINDINGS
Twelve studies met the inclusion criteria. Irisin injection in rodents significantly reduced neuroinflammation, cytokine cascades, and neurodegeneration. It also protected neurons from damage and apoptosis, reduced oxidative stress, blood-brain barrier disruption, and neurobehavioral deficits following disease or injury. Various mechanisms were suggested to be responsible for these neuroprotective effects. Most of the included studies presented a low risk of bias based on SYRCLE's Risk of Bias tool. Irisin injection demonstrated the potential to alleviate neuroinflammation and counteract neurodegeneration in rodent models through multiple pathways. However, further research is needed to fully understand its mechanism of action and its potential applications in clinical practice and drug discovery.
Topics: Animals; Fibronectins; Neuroprotective Agents; Neuroinflammatory Diseases; Exercise; Brain
PubMed: 38176582
DOI: 10.1016/j.lfs.2023.122393