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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 -
Ophthalmology and Therapy Jul 2024This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function....
INTRODUCTION
This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function. Since PAs often impair vision as a result of their location near visual structures, this research is key to understanding and improving vision recovery after surgery.
METHODS
Our study is based on a retrospective analysis of the historical data of 28 patients diagnosed with pituitary adenomas. We conducted assessments by reviewing preoperative and postoperative imaging records. These included optical coherence tomography (OCT) for retinal structure analysis, diffusion tensor imaging (DTI) for neural transmission evaluation, and optical coherence tomography angiography for assessing blood vessel density. These tools allowed for a detailed understanding of the structural and functional changes within the visual pathway following PA surgery.
RESULTS
OCT findings show postoperative changes in the eye: thinning in average and nasal circumpapillary retinal nerve fiber layer, thickening in macular central 1 mm inner plexus layer, ganglion cell complex, and nasal retinal nerve fiber layer. DTI reveals increased fractional anisotropy (FA) in the left optic chiasm and posterior optic nerve, decreased mid-segment optic nerve FA, and increased apparent diffusion coefficient (ADC) in the right optic chiasm and nerve segments. Early postoperative reduction in radial peripapillary capillaries plexus density is noted. Preoperative ganglion cell layer (GCL) thickness correlates with postoperative visual radiation FA and ADC values, especially in the inferior quadrant. A negative correlation exists between preoperative GCL thickness and postoperative visual field mean defect values, particularly on the temporal side and superior inner ring. All changes are statistically significant (P < 0.05).
CONCLUSIONS
The study finds that surgery for PA has varied effects on vision. Early post surgery, there are changes in the retina and nerve signals. Macular GCL thickness before surgery might predict early visual recovery, influencing future research and treatment for vision issues related to PA.
PubMed: 38822193
DOI: 10.1007/s40123-024-00966-3 -
Scientific Reports May 2024In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual...
In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.
Topics: Animals; Rats; Mice; Male; Retinal Ganglion Cells; Photic Stimulation; Female; Contrast Sensitivity; Behavior, Animal; Retinal Cone Photoreceptor Cells; Mice, Inbred C57BL; Visual Perception; Fear; Retina; Visual Pathways
PubMed: 38822033
DOI: 10.1038/s41598-024-63458-1 -
Neural Regeneration Research Feb 2025Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration. It causes local damage to photoreceptors, retinal pigment epithelium, and...
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration. It causes local damage to photoreceptors, retinal pigment epithelium, and choroidal vessels, which leads to permanent central vision loss of patients with neovascular age-related macular degeneration. The pathogenesis of subretinal fibrosis is complex, and the underlying mechanisms are largely unknown. Therefore, there are no effective treatment options. A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments. The current article reviews several aspects of subretinal fibrosis, including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis; multimodal imaging techniques for subretinal fibrosis; animal models for studying subretinal fibrosis; cellular and non-cellular constituents of subretinal fibrosis; pathophysiological mechanisms involved in subretinal fibrosis, such as aging, infiltration of macrophages, different sources of mesenchymal transition to myofibroblast, and activation of complement system and immune cells; and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis, such as vascular endothelial growth factor, connective tissue growth factor, fibroblast growth factor 2, platelet-derived growth factor and platelet-derived growth factor receptor-β, transforming growth factor-β signaling pathway, Wnt signaling pathway, and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10. This review will improve the understanding of the pathogenesis of subretinal fibrosis, allow the discovery of molecular targets, and explore potential treatments for the management of subretinal fibrosis.
PubMed: 38819041
DOI: 10.4103/NRR.NRR-D-23-01642 -
Nature Communications May 2024Object recognition and categorization are essential cognitive processes which engage considerable neural resources in the human ventral visual stream. However, the...
Object recognition and categorization are essential cognitive processes which engage considerable neural resources in the human ventral visual stream. However, the tuning properties of human ventral stream neurons for object shape and category are virtually unknown. We performed large-scale recordings of spiking activity in human Lateral Occipital Complex in response to stimuli in which the shape dimension was dissociated from the category dimension. Consistent with studies in nonhuman primates, the neuronal representations were primarily shape-based, although we also observed category-like encoding for images of animals. Surprisingly, linear decoders could reliably classify stimulus category even in data sets that were entirely shape-based. In addition, many recording sites showed an interaction between shape and category tuning. These results represent a detailed study on shape and category coding at the neuronal level in the human ventral visual stream, furnishing essential evidence that reconciles human imaging and macaque single-cell studies.
Topics: Humans; Visual Cortex; Neurons; Photic Stimulation; Male; Female; Pattern Recognition, Visual; Adult; Animals; Young Adult; Visual Pathways
PubMed: 38816391
DOI: 10.1038/s41467-024-49078-3 -
European Journal of Pharmacology May 2024Corneal neovascularization (CoNV) is predominantly initiated by inflammatory processes, resulting in aberrant vascular proliferation and consequent visual impairment....
Corneal neovascularization (CoNV) is predominantly initiated by inflammatory processes, resulting in aberrant vascular proliferation and consequent visual impairment. Existing therapeutic interventions for CoNV demonstrate limited efficacy and potential for adverse reactions. Protein arginine methyltransferase 1 (PRMT1) is associated with the regulation of inflammation and M2 macrophage polarization. Nevertheless, the precise mechanism by which PRMT1 operates in CoNV remains uncertain. This study explored the impact of PRMT1 inhibition in a murine model of CoNV induced by alkali burn. Our findings indicated a direct relationship between PRMT1 levels and corneal damage. Moreover, our observations indicated an increase in fibroblast growth factor 2 (FGF2) expression in CoNV, which was reduced after treatment with a PRMT1 inhibitor. The inhibition of PRMT1 alleviated both corneal injury and CoNV, as evidenced by decreased corneal opacity and neovascularization. Immunofluorescence analysis and evaluation of inflammatory factor expression demonstrated that PRMT1 inhibition attenuated M2 macrophage polarization, a phenomenon that was reversed by the administration of recombinant FGF2 protein. These results were confirmed through experimentation on Human Umbilical Vein Endothelial Cells (HUVECs) and Mouse leukemia cells of monocyte macrophage cells (RAW264.7). Furthermore, it was established that FGF2 played a role in PI3K/Akt signal transduction, a critical regulatory pathway for M2 macrophage polarization. Importantly, the activity of this pathway was found to be suppressed by PRMT1 inhibitors. Mechanistically, PRMT1 was shown to promote M2 macrophage polarization, thereby contributing to CoNV, through the FGF2/PI3K/Akt pathway. Therefore, targeting PRMT1 may offer a promising therapeutic approach.
PubMed: 38815785
DOI: 10.1016/j.ejphar.2024.176673 -
Frontiers in Bioscience (Landmark... May 2024Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the... (Review)
Review
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.
Topics: Humans; PTEN Phosphohydrolase; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; MicroRNAs; Tumor Microenvironment; Cell Proliferation; Apoptosis; Gene Expression Regulation, Neoplastic; RNA, Long Noncoding; Autophagy; Cell Movement; RNA, Circular; Herpesvirus 4, Human; Signal Transduction
PubMed: 38812313
DOI: 10.31083/j.fbl2905179 -
Proceedings. Biological Sciences May 2024The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and...
The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and irradiances are higher. Although melanopsin and cone photoresponses can be mediated via separate pathways, the connectivity of melanopsin cells across all levels of the retina enables them to modify cone signals. The downstream effects of melanopsin-cone interactions on human vision are however, incompletely understood. Here, we determined how the change in daytime melanopsin activation affects the human cone pathway signals in the visual cortex. A 5-primary silent-substitution method was developed to evaluate the dependence of cone-mediated signals on melanopsin activation by spectrally tuning the lights and stabilizing the rhodopsin activation under a constant cone photometric luminance. The retinal (white noise electroretinogram) and cortical responses (visual evoked potential) were simultaneously recorded with the photoreceptor-directed lights in 10 observers. By increasing the melanopsin activation, a reverse response pattern was observed with cone signals being supressed in the retina by 27% ( = 0.03) and subsequently amplified by 16% ( = 0.01) as they reach the cortex. We infer that melanopsin activity can amplify cone signals at sites distal to retinal bipolar cells to cause a decrease in the psychophysical Weber fraction for cone vision.
Topics: Humans; Rod Opsins; Retinal Cone Photoreceptor Cells; Visual Cortex; Adult; Electroretinography; Evoked Potentials, Visual; Female; Male; Young Adult; Photic Stimulation
PubMed: 38808443
DOI: 10.1098/rspb.2023.2708 -
Frontiers in Neuroscience 2024The caudolateral nidopallium (NCL, an analog of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in corvids (a songbird), whereas...
The caudolateral nidopallium (NCL, an analog of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in corvids (a songbird), whereas the involvement of other brain regions in these phenomena is not well explored. We used house crows () to explore the neural correlates of learning and decision-making by initially training them on a shape discrimination task followed by immunohistochemistry to study the immediate early gene expression (Arc), a dopaminoceptive neuronal marker (DARPP-32, Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa) to understand the involvement of the reward pathway and an immature neuronal marker (DCX, doublecortin) to detect learning-induced changes in adult neurogenesis. We performed neuronal counts and neuronal tracing, followed by morphometric analyses. Our present results have demonstrated that besides NCL, other parts of the caudal nidopallium (NC), avian basal ganglia, and intriguingly, vocal control regions in house crows are involved in visual discrimination. We have also found that training on the visual discrimination task can be correlated with neurite pruning in mature dopaminoceptive neurons and immature DCX-positive neurons in the NC of house crows. Furthermore, there is an increase in the incorporation of new neurons throughout NC and the medial striatum which can also be linked to learning. For the first time, our results demonstrate that a combination of structural changes in mature and immature neurons and adult neurogenesis are linked to learning in corvids.
PubMed: 38808028
DOI: 10.3389/fnins.2024.1359874