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Brain Structure & Function Jul 2024Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by...
Selective activations and functional connectivities to the sight of faces, scenes, body parts and tools in visual and non-visual cortical regions leading to the human hippocampus.
Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by measuring selective fMRI activations and functional connectivity increases to stationary visual stimuli of faces, scenes, body parts and tools from 956 HCP participants. Faces activate regions in the ventrolateral visual cortical stream (FFC), in the superior temporal sulcus (STS) visual stream for face and head motion; and inferior parietal visual (PGi) and somatosensory (PF) regions. Scenes activate ventromedial visual stream VMV and PHA regions in the parahippocampal scene area; medial (7m) and lateral parietal (PGp) regions; and the reward-related medial orbitofrontal cortex. Body parts activate the inferior temporal cortex object regions (TE1p, TE2p); but also visual motion regions (MT, MST, FST); and the inferior parietal visual (PGi, PGs) and somatosensory (PF) regions; and the unpleasant-related lateral orbitofrontal cortex. Tools activate an intermediate ventral stream area (VMV3, VVC, PHA3); visual motion regions (FST); somatosensory (1, 2); and auditory (A4, A5) cortical regions. The findings add function to cortical connectivity maps; and show how stationary visual stimuli activate other cortical regions related to their associations, including visual motion, somatosensory, auditory, semantic, and orbitofrontal cortex value-related, regions.
Topics: Humans; Magnetic Resonance Imaging; Male; Female; Adult; Brain Mapping; Hippocampus; Young Adult; Photic Stimulation; Connectome; Face; Neural Pathways; Visual Cortex; Visual Perception; Pattern Recognition, Visual
PubMed: 38839620
DOI: 10.1007/s00429-024-02811-6 -
Investigative Ophthalmology & Visual... Jun 2024Optic pathway gliomas (OPGs) are most predominant pilocytic astrocytomas, which are typically diagnosed within the first decade of life. The majority of affected... (Review)
Review
Optic pathway gliomas (OPGs) are most predominant pilocytic astrocytomas, which are typically diagnosed within the first decade of life. The majority of affected children with OPGs also present with neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome. OPGs in individuals with NF1 primarily affect the optic pathway and lead to visual disturbance. However, it is challenging to assess risk in asymptomatic patients without valid biomarkers. On the other hand, for symptomatic patients, there is still no effective treatment to prevent or recover vision loss. Therefore, this review summarizes current knowledge regarding the pathogenesis of NF1-associated OPGs (NF1-OPGs) from preclinical studies to seek potential prognostic markers and therapeutic targets. First, the loss of the NF1 gene activates 3 distinct Ras effector pathways, including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP pathway, which mediate glioma tumorigenesis. Meanwhile, non-neoplastic cells from the tumor microenvironment (microglia, T cells, neurons, etc.) also contribute to gliomagenesis via various soluble factors. Subsequently, we investigated potential genetic risk factors, molecularly targeted therapies, and neuroprotective strategies for tumor prevention and vision recovery. Last, potential directions and promising preclinical models of NF1-OPGs are presented for further research. On the whole, NF1-OPGs develop as a result of the interaction between glioma cells and the tumor microenvironment. Developing effective treatments require a better understanding of tumor molecular characteristics, as well as multistage interventions targeting both neoplastic cells and non-neoplastic cells.
Topics: Humans; Neurofibromatosis 1; Optic Nerve Glioma; Risk Factors; Animals; Neurofibromin 1; Optic Nerve Neoplasms
PubMed: 38837168
DOI: 10.1167/iovs.65.6.8 -
Progress in Neurobiology Jul 2024We develop further here the only quantitative theory of the storage of information in the hippocampal episodic memory system and its recall back to the neocortex. The... (Review)
Review
We develop further here the only quantitative theory of the storage of information in the hippocampal episodic memory system and its recall back to the neocortex. The theory is upgraded to account for a revolution in understanding of spatial representations in the primate, including human, hippocampus, that go beyond the place where the individual is located, to the location being viewed in a scene. This is fundamental to much primate episodic memory and navigation: functions supported in humans by pathways that build 'where' spatial view representations by feature combinations in a ventromedial visual cortical stream, separate from those for 'what' object and face information to the inferior temporal visual cortex, and for reward information from the orbitofrontal cortex. Key new computational developments include the capacity of the CA3 attractor network for storing whole charts of space; how the correlations inherent in self-organizing continuous spatial representations impact the storage capacity; how the CA3 network can combine continuous spatial and discrete object and reward representations; the roles of the rewards that reach the hippocampus in the later consolidation into long-term memory in part via cholinergic pathways from the orbitofrontal cortex; and new ways of analysing neocortical information storage using Potts networks.
Topics: Humans; Hippocampus; Animals; Models, Neurological; Memory, Episodic
PubMed: 38834132
DOI: 10.1016/j.pneurobio.2024.102636 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024The two visual pathways model posits that visual information is processed through two distinct cortical systems: The ventral pathway promotes visual recognition, while...
The two visual pathways model posits that visual information is processed through two distinct cortical systems: The ventral pathway promotes visual recognition, while the dorsal pathway supports visuomotor control. Recent evidence suggests the dorsal pathway is also involved in shape processing and may contribute to object perception, but it remains unclear whether this sensitivity is independent of attentional mechanisms that were localized to overlapping cortical regions. To address this question, we conducted two fMRI experiments that utilized different parametric scrambling manipulations in which human participants viewed novel objects in different levels of scrambling and were instructed to attend to either the object or to another aspect of the image (e.g. color of the background). Univariate and multivariate analyses revealed that the large-scale organization of shape selectivity along the dorsal and ventral pathways was preserved regardless of the focus of attention. Attention did modulate shape sensitivity, but these effects were similar across the two pathways. These findings support the idea that shape processing is at least partially dissociable from attentional processes and relies on a distributed set of cortical regions across the visual pathways.
Topics: Humans; Attention; Male; Female; Visual Pathways; Adult; Young Adult; Magnetic Resonance Imaging; Photic Stimulation; Brain Mapping; Pattern Recognition, Visual; Form Perception; Visual Cortex
PubMed: 38832533
DOI: 10.1093/cercor/bhae221 -
International Wound Journal Jun 2024To assess all published studies which describe what happens to the delivery of pressure ulcer/injury (PI/PU) care pathways as a result of detecting raised sub-epidermal... (Review)
Review
To assess all published studies which describe what happens to the delivery of pressure ulcer/injury (PI/PU) care pathways as a result of detecting raised sub-epidermal moisture (SEM) delta (∆ ≥ 0.6). We undertook a systematic review of the literature, and included original research studies using either a prospective or retrospective study design that report the impact that assessment using SEM assessments have on healthcare practitioners' delivery of PI/PU care pathways in adults at risk of developing PI/PUs. The review protocol was registered on PROSPERO (CRD42023416975). A literature search was conducted in May 2023, using PubMed, CINAHL, Scopus, Cochrane, EMBASE, Web of Science and Science Direct databases. Data were extracted using a data extraction tool including elements such as country, setting, sample size, intervention, control and quality appraisal was undertaken using the Evidence-based Librarianship. We identified nine papers published between 2017 and 2022. The majority of these studies were conducted in England (n = 6; 67%). The systematic review included studies conducted across multiple care settings including acute care, medical-surgical units, and palliative care, highlighting the importance of PI/PU prevention and management across diverse patient populations. The PI/PU care pathways implemented in the studies varied, but commonly included elements such as the application or increased use of pressure-redistributing mattresses/cushions, implementation of repositioning plans, management of incontinence and moisture, regular skin inspection, and assessment of patient mobility. Out of the nine studies identified, seven reported PI/PU incidence. A meta-analysis of seven studies (N = 18 451) demonstrated a statistically significant reduction in visual PI/PU development in favour of SEM-guided care pathways compared to usual care (the odds ratio = 0.36 [95% confidence interval: 0.24-0.53, p < 0.00001]). This systematic review provides evidence that implementing SEM assessments in patients at risk of developing PI/PUs prompts anatomy-specific clinical actions. The subsequent implementation of enhanced and targeted skin care interventions leads to consistent and sustained reductions in hospital-acquired PU incidence. The findings emphasise the importance of incorporating SEM assessments as part of comprehensive PI/PU prevention strategies in all care settings and patient populations. This systematic review is limited by the predominance of observational studies and variable study quality. Future research should focus on randomised trials in different care settings that monitor the efficacy of preventive interventions and their impact in reducing PI/PU incidence when implemented based on SEM assessments.
Topics: Pressure Ulcer; Humans; Male; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Critical Pathways; Delivery of Health Care
PubMed: 38832363
DOI: 10.1111/iwj.14928 -
Molecular Therapy. Nucleic Acids Jun 2024Retinal ischemia is a common clinical event leading to retinal ganglion cell (RGC) death, resulting in irreversible vision loss. In the retina, glia-neuron communication...
Retinal ischemia is a common clinical event leading to retinal ganglion cell (RGC) death, resulting in irreversible vision loss. In the retina, glia-neuron communication is crucial for multiple functions and homeostasis. Extracellular vesicles, notably exosomes, play a critical role. The functions and mechanisms of retinal astrocyte-secreted exosomes remain unclear. Here, we isolated astrocyte-derived exosomes under hypoxia or normoxia and explored their role in an retinal ischemia-reperfusion (RIR) model. We found that hypoxia triggered astrocytes to produce a significantly increased number of exosomes, which could be internalized by RGCs or . Also, in the RIR model, the hypoxia-induced exosomes ameliorated the RIR injury and suppressed the RGC apoptosis. Furthermore, microRNA sequencing of retinal astrocyte-secreted exosomes revealed different patterns of exosomal miRNAs under hypoxia, particularly enriched with miR-329-5p. We verified that miR-329-5p was specifically bound to mitogen-activated protein kinase 8 mRNA, and subsequent JNK-pathway molecules were downregulated. We anticipated that the miR-329-5p/JNK pathway is a key to suppressing RGC apoptosis and preventing RIR injury. Such findings provided insights into the therapeutic potential of hypoxia-induced astrocyte-secreted exosomes and the miR-329-5p for treating retina ischemic diseases.
PubMed: 38831900
DOI: 10.1016/j.omtn.2024.102209 -
Scientific Reports Jun 2024Keratoconus is corneal disease in which the progression of conical dilation of cornea leads to reduced visual acuity and even corneal perforation. However, the etiology...
Keratoconus is corneal disease in which the progression of conical dilation of cornea leads to reduced visual acuity and even corneal perforation. However, the etiology mechanism of keratoconus is still unclear. This study aims to identify the signature genes related to cell death in keratoconus and examine the function of these genes. A dataset of keratoconus from the GEO database was analysed to identify the differentially expressed genes (DEGs). A total of 3558 DEGs were screened from GSE151631. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they mainly involved in response to hypoxia, cell-cell adhesion, and IL-17 signaling pathway. Then, the cell death-related genes datasets were intersected with the above 3558 DEGs to obtain 70 ferroptosis-related DEGs (FDEGs), 32 autophagy-related DEGs (ADEGs), six pyroptosis-related DEGs (PDEGs), four disulfidptosis-related DEGs (DDEGs), and one cuproptosis-related DEGs (CDEGs). After using Least absolute shrinkage and selection operator (LASSO), Random Forest analysis, and receiver operating characteristic (ROC) curve analysis, one ferroptosis-related gene (TNFAIP3) and five autophagy-related genes (CDKN1A, HSPA5, MAPK8IP1, PPP1R15A, and VEGFA) were screened out. The expressions of the above six genes were significantly decreased in keratoconus and the area under the curve (AUC) values of these genes was 0.944, 0.893, 0.797, 0.726, 0.882 and 0.779 respectively. GSEA analysis showed that the above six genes mainly play an important role in allograft rejection, asthma, and circadian rhythm etc. In conclusion, the results of this study suggested that focusing on these genes and autoimmune diseases will be a beneficial perspective for the keratoconus etiology research.
Topics: Keratoconus; Humans; Computational Biology; Gene Expression Profiling; Gene Ontology; Cell Death; Gene Regulatory Networks; Ferroptosis; Databases, Genetic; Transcriptome; Protein Interaction Maps
PubMed: 38830963
DOI: 10.1038/s41598-024-63109-5 -
Frontiers in Pharmacology 2024Retinal pigment epithelial cell and neuroretinal damage in age-related macular degeneration (AMD) can lead to serious visual impairments and blindness. Studies have... (Review)
Review
Retinal pigment epithelial cell and neuroretinal damage in age-related macular degeneration (AMD) can lead to serious visual impairments and blindness. Studies have shown that mitophagy, a highly specialized cellular degradation system, is implicated in the pathogenesis of AMD. Mitophagy selectively eliminates impaired or non-functioning mitochondria via several pathways, such as the phosphatase and tensin homolog-induced kinase 1/Parkin, BCL2-interacting protein 3 and NIP3-like protein X, FUN14 domain-containing 1, and AMP-activated protein kinase pathways. This has a major impact on the maintenance of mitochondrial homeostasis. Therefore, the regulation of mitophagy could be a promising therapeutic strategy for AMD. Traditional Chinese medicine (TCM) uses natural products that could potentially prevent and treat various diseases, such as AMD. This review aims to summarize recent findings on mitophagy regulation pathways and the latest progress in AMD treatment targeting mitophagy, emphasizing methods involving TCM.
PubMed: 38828456
DOI: 10.3389/fphar.2024.1410998 -
BioRxiv : the Preprint Server For... May 2024Current clinical trials are investigating gamma frequency sensory stimulation as a potential therapeutic strategy for Alzheimer's disease, yet we lack a comprehensive...
BACKGROUND
Current clinical trials are investigating gamma frequency sensory stimulation as a potential therapeutic strategy for Alzheimer's disease, yet we lack a comprehensive picture of the effects of this stimulation on multiple aspects of brain function. While most prior research has focused on gamma frequency sensory stimulation, we previously showed that exposing mice to visual flickering stimulation increased MAPK and NFκB signaling in the visual cortex in a manner dependent on duration and frequency of sensory stimulation exposure. Because these pathways control multiple neuronal and glial functions and are differentially activated based on the duration and frequency of flicker stimulation, we aimed to define the transcriptional effects of different frequencies and durations of flicker stimulation on multiple brain functions.
METHODS
We exposed 5xFAD mice to different frequencies of audio/visual flicker stimulation (constant light, 10Hz, 20Hz, 40Hz) for durations of 0.5hr, 1hr, or 4hr, then used bulk RNAseq to profile transcriptional changes within the visual cortex and hippocampus tissues. Using weighted gene co-expression network analysis, we identified modules of co-expressed genes controlled by frequency and/or duration of stimulation.
RESULTS
Within the visual cortex, we found that all stimulation frequencies caused fast activation of a module of immune genes within 1hr and slower suppression of synaptic genes after 4hrs of stimulation. Interestingly, all frequencies of stimulation led to slow suppression of astrocyte specific gene sets, while activation of neuronal gene sets was frequency and duration specific. In contrast, in the hippocampus, immune and synaptic modules were suppressed based on the frequency of stimulation. Specifically,10Hz activated a module of genes associated with mitochondrial function, metabolism, and synaptic translation while 10Hz rapidly suppressed a module of genes linked to neurotransmitter activity.
CONCLUSION
Collectively, our data indicate that the frequency and duration of flicker stimulation controls immune, neuronal, and metabolic genes in multiple regions of the brain affected by Alzheimer's disease. Flicker stimulation may thus represent a potential therapeutic strategy that can be tuned based on the brain region and the specific cellular process to be modulated.
PubMed: 38826251
DOI: 10.1101/2024.05.20.594705 -
Aquatic Toxicology (Amsterdam,... Jul 2024Thyroid hormones (THs) act early in ontogenesis, even prior to the differentiation of thyrocytes. Maternal transfer of THs is therefore known to play an essential role...
The generation gap in endocrine disruption: Can the integrated fish endocrine disruptor test (iFEDT) bridge the gap by assessing intergenerational effects of thyroid hormone system disruption?
Thyroid hormones (THs) act early in ontogenesis, even prior to the differentiation of thyrocytes. Maternal transfer of THs is therefore known to play an essential role in early development. Current OECD test guidelines for the assessment of TH system disruption (THSD) do not address inter- or transgenerational effects. The integrated fish endocrine disruptor test (iFEDT), a test combining parental and developmental exposure of filial fish, may fill this gap. We tested the ability of the iFEDT to detect intergenerational effects in zebrafish (Danio rerio): Parental fish were exposed to propylthiouracil (PTU), an inhibitor of TH synthesis, or not exposed. The offspring was submitted to a crossed experimental design to obtain four exposure scenarios: (1) no exposure at all, (2) parental exposure only, (3) embryonic exposure only, and (4) combined parental and embryonic exposure. Swim bladder inflation, visual motor response (VMR) and gene expression of the progeny were analysed. Parental, but not embryonic PTU exposure reduced the size of the swim bladder of 5 d old embryos, indicating the existence of intergenerational effects. The VMR test produced opposite responses in 4.5 d old embryos exposed to PTU vs. embryos derived from exposed parents. Embryonic exposure, but not parental exposure increased gene expression of thyroperoxidase, the target of PTU, most likely due to a compensatory mechanism. The gene expression of pde-6h (phosphodiesterase) was reduced by embryonic, but not parental exposure, suggesting downregulation of phototransduction pathways. Hence, adverse effects on swim bladder inflation appear more sensitive to parental than embryonic exposure and the iFEDT represents an improvement in the testing strategy for THSD.
Topics: Animals; Endocrine Disruptors; Zebrafish; Thyroid Hormones; Water Pollutants, Chemical; Propylthiouracil; Female; Embryo, Nonmammalian; Male; Toxicity Tests
PubMed: 38824743
DOI: 10.1016/j.aquatox.2024.106969