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The Journal of Neuroscience : the... Jun 2024
Review
Topics: Animals; Visual Pathways; Synapses; Retina; Humans
PubMed: 38897733
DOI: 10.1523/JNEUROSCI.0383-24.2024 -
Experimental Eye Research Jun 2024This review examines the pivotal role of photoreceptor cells in ocular refraction development, focusing on dopamine (DA) as a key neurotransmitter. Contrary to the... (Review)
Review
This review examines the pivotal role of photoreceptor cells in ocular refraction development, focusing on dopamine (DA) as a key neurotransmitter. Contrary to the earlier view favoring cone cells, recent studies have highlighted the substantial contributions of both rod and cone cells to the visual signaling pathways that influence ocular refractive development. Notably, rod cells appeared to play a central role. Photoreceptor cells interact intricately with circadian rhythms, color vision pathways, and other neurotransmitters, all of which are crucial for the complex mechanisms driving the development of myopia. This review emphasizes that ocular refractive development results from a coordinated interplay between diverse cell types, signaling pathways, and neurotransmitters. This perspective has significant implications for unraveling the complex mechanisms underlying myopia and aiding in the development of more effective prevention and treatment strategies.
PubMed: 38897270
DOI: 10.1016/j.exer.2024.109976 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss...
Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.
Topics: Humans; Female; Male; Hearing Loss, Unilateral; Middle Aged; Adult; Connectome; Brain; Neuroma, Acoustic; Neural Pathways; Magnetic Resonance Imaging; Aged; Diffusion Tensor Imaging; Functional Laterality; Nerve Net
PubMed: 38896551
DOI: 10.1093/cercor/bhae220 -
Brain and Behavior Jun 2024Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc)....
INTRODUCTION
Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks.
METHODS
MDD participants (n = 58, mean age = 40.7 years, female = 28) received four ketamine infusions (0.5 mg/kg) 2-3 times weekly. Resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments were collected at baseline and 24 h post-SKI. Static FC (sFC) and dynamic FC variability (dFCv) were calculated from left and right Hb and NAc seeds to all other brain regions. Changes in FC pre-to-post SKI, and correlations with changes with mood and anhedonia were examined. Comparisons of FC between patients and healthy controls (HC) at baseline (n = 55, mean age = 32.6, female = 31), and between HC assessed twice (n = 16) were conducted as follow-up analyses.
RESULTS
Following SKI, significant increases in left Hb-bilateral visual cortex FC, decreases in left Hb-left inferior parietal cortex FC, and decreases in left NAc-right cerebellum FC occurred. Decreased dFCv between left Hb and right precuneus and visual cortex, and decreased dFCv between right NAc and right visual cortex both significantly correlated with improvements in mood ratings. Decreased FC between left Hb and bilateral visual/parietal cortices as well as increased FC between left NAc and right visual/parietal cortices both significantly correlated with improvements in anhedonia. No differences were observed between HC at baseline or over time.
CONCLUSION
Subanesthetic ketamine modulates functional pathways linking the Hb and NAc with visual, parietal, and cerebellar regions in MDD. Overlapping effects between Hb and NAc functional systems were associated with ketamine's therapeutic response.
Topics: Humans; Ketamine; Male; Depressive Disorder, Major; Nucleus Accumbens; Adult; Female; Habenula; Magnetic Resonance Imaging; Middle Aged; Antidepressive Agents; Anhedonia
PubMed: 38894648
DOI: 10.1002/brb3.3511 -
Sensors (Basel, Switzerland) May 2024Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding...
Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk's motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk's motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.
Topics: Humans; Stroke Rehabilitation; Male; Feedback, Sensory; Robotics; Female; Middle Aged; Arm; Stroke; Movement; Adult; Exercise Therapy; Torso; Aged; Survivors; Upper Extremity
PubMed: 38894119
DOI: 10.3390/s24113331 -
International Journal of Molecular... Jun 2024The first member of the arrestin family, visual arrestin-1, was discovered in the late 1970s. Later, the other three mammalian subtypes were identified and cloned. The... (Review)
Review
The first member of the arrestin family, visual arrestin-1, was discovered in the late 1970s. Later, the other three mammalian subtypes were identified and cloned. The first described function was regulation of G protein-coupled receptor (GPCR) signaling: arrestins bind active phosphorylated GPCRs, blocking their coupling to G proteins. It was later discovered that receptor-bound and free arrestins interact with numerous proteins, regulating GPCR trafficking and various signaling pathways, including those that determine cell fate. Arrestins have no enzymatic activity; they function by organizing multi-protein complexes and localizing their interaction partners to particular cellular compartments. Today we understand the molecular mechanism of arrestin interactions with GPCRs better than the mechanisms underlying other functions. However, even limited knowledge enabled the construction of signaling-biased arrestin mutants and extraction of biologically active monofunctional peptides from these multifunctional proteins. Manipulation of cellular signaling with arrestin-based tools has research and likely therapeutic potential: re-engineered proteins and their parts can produce effects that conventional small-molecule drugs cannot.
Topics: Humans; Animals; Arrestins; Signal Transduction; Receptors, G-Protein-Coupled; Protein Binding; Phosphorylation
PubMed: 38892473
DOI: 10.3390/ijms25116284 -
International Journal of Molecular... May 2024Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often... (Review)
Review
Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.
Topics: Humans; Endothelial Cells; Wet Macular Degeneration; Animals; Vascular Endothelial Growth Factor A; Ranibizumab; Angiogenesis Inhibitors; Metabolic Networks and Pathways; Neovascularization, Pathologic
PubMed: 38892113
DOI: 10.3390/ijms25115926 -
Neural Development Jun 2024The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state...
The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development.Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2-4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2-4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4-6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry.
Topics: Animals; Geniculate Bodies; Mice; Thalamic Nuclei; Visual Pathways; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways
PubMed: 38890758
DOI: 10.1186/s13064-024-00183-5 -
Endocrinology Jun 2024Thyroid hormone (TH) effects are mediated through TH receptors (TRs) TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes...
Thyroid hormone (TH) effects are mediated through TH receptors (TRs) TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes (canonical signaling). In addition, they mediate activation of signaling pathways (noncanonical signaling). Whether noncanonical TR action contributes to the spectrum of TH effects is largely unknown. Aim of this study was to attribute physiological effects to the TR isoforms and their canonical and noncanonical signaling. We conducted multi-parameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to mutations in the TR DNA-binding domain (TRαGS, TRβGS) and their wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity, retinal thickness (TRα and TRβ) and in muscle metabolism (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization or increased anxiety related behavior were only observed in TRαKO, but not TRαGS mice. Noncanonical TRα action improved energy utilization and prevented hyperphagia observed in female TRαKO mice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA-binding-deficient mutants and wild-type counterparts, we could establish that the noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions and, thus, contribute to the spectrum of physiological TH effects.
PubMed: 38889231
DOI: 10.1210/endocr/bqae067 -
Circulation. Cardiovascular Imaging Jun 2024Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely... (Clinical Trial)
Clinical Trial
BACKGROUND
Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD).
METHODS
Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80).
RESULTS
About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [=0.03]) without compromising specificity (77% versus 74% [=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted.
CONCLUSIONS
CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.
Topics: Aged; Female; Humans; Male; Middle Aged; Blood Flow Velocity; Computed Tomography Angiography; Coronary Angiography; Coronary Circulation; Coronary Stenosis; Coronary Vessels; Fractional Flow Reserve, Myocardial; Myocardial Perfusion Imaging; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Thermodilution
PubMed: 38889213
DOI: 10.1161/CIRCIMAGING.124.016635