Cell types and cell circuits in human and non-human primate retina

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 78, P. 100844 - 100844

Published: Feb. 5, 2020

This review summarizes our current knowledge of primate including human retina focusing on bipolar, amacrine and ganglion cells their connectivity. We have two main motivations in writing. Firstly, recent progress non-invasive imaging methods to study retinal diseases mean that better understanding the is becoming an important goal both for basic clinical sciences. Secondly, genetically modified mice are increasingly used as animal models diseases. Thus, it understand which extent retinas primates rodents comparable. first compare cell populations rodent retinas, with emphasis how fovea (despite its small size) dominates neural landscape retina. next summarise what known, not about postreceptoral neurone The inventories bipolar now nearing completion, comprising ~12 types at least 17 cell. Primate show clear differences dendritic field size across retina, morphology differs clearly from mouse cells. Compared cells, even higher morphological diversity: they could comprise over 40 types. Many appear conserved between mice, but functions only a few understood any or non-primate Amacrine final frontier research monkeys alike.

Language: Английский

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Crosstalk: The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image‐forming and non‐image‐forming vision

The Journal of Comparative Neurology, Journal Year: 2020, Volume and Issue: 528(12), P. 2044 - 2067

Published: Jan. 31, 2020

Melanopsin ganglion cells have defied convention since their discovery almost 20 years ago. In the following, many types of these intrinsically photosensitive retinal (ipRGCs) emerged. mouse retina, there are currently six known (M1-M6) melanopsin cells, each with unique morphology, mosaics, connections, physiology, projections, and functions. While melanopsin-expressing usually associated behaviors like circadian photoentrainment pupillary light reflex, characterization multiple has demonstrated a reach that may extend far beyond non-image-forming vision. fact, studies shown individual potential to impact image-forming functions contrast sensitivity color opponency. Thus, goal this review is summarize morphological functional aspects in retina highlight respective roles Although cell do project brain targets, it important note only first step determining influence on Even so, visual system canonically been divided into two realms begun challenge boundary between them, providing an overlap information complementary rather than redundant. Further photoreceptors will no doubt continue illustrate ever-expanding role for

Language: Английский

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Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma

Journal of Pineal Research, Journal Year: 2021, Volume and Issue: 70(4)

Published: March 17, 2021

Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin promising substance ameliorate glaucoma-associated compromised rhythms, sleep, mood, function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long-term (daily at 10:30 pm for 90 days) oral administration on systemic (Tb) local organ vision (IOP) pattern electroretinogram (PERG), depending stage patients diagnosed stable or advanced primary open-angle glaucoma. laboratory study 15 them, 24-hour records salivary were obtained MTNR1B receptor gene polymorphism was assessed. increased stability Tb rhythm by improving its phase alignment IOP. time-dependently decreased IOP standard deviation (SD). mean SD decreases more pronounced individuals higher initial mean. improved RGCs function glaucoma; N95 amplitude increase correlated positively loss. The beneficial sleep mood greater Finally, delayed phases observed G-allele carriers Combined, these results provide evidence efficiency restoring rhythms different vs. indicating that personalized strategy may further refine treatment benefits.

Language: Английский

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Roles of clock genes in the pathogenesis of Parkinson's disease

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 74, P. 101554 - 101554

Published: Dec. 30, 2021

Language: Английский

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Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4401 - 4401

Published: April 16, 2024

The circadian rhythms generated by the master biological clock located in brain's hypothalamus influence central physiological processes. At molecular level, a core set of genes interact to form transcription-translation feedback loops that provide basis rhythm. In animal models disease, desynchronization peripheral tissues with has been detected. Interestingly, patients vascular dementia have sleep disorders and irregular patterns. These alterations impact hormonal levels, cardiovascular health (including blood pressure regulation vessel function), pattern expression activity antioxidant enzymes. Additionally, oxidative stress can arise from ischemia-reperfusion injury, amyloid-beta production, abnormal phosphorylation tau protein, neurotransmitters, among others. Several signaling pathways are involved pathogenesis dementia. While precise mechanisms linking still being studied, there is evidence suggest maintaining healthy patterns supporting proper rhythm function may be important for reducing risk Here, we reviewed main action targets related cycle

Language: Английский

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Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1086 - 1086

Published: May 30, 2022

Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration retina, ultimately leading to loss visual function. Oxidative stress inflammation play fundamental roles in physiopathology these diseases. Photoreceptor cell death induces an inflammatory state retina. The activation several molecular pathways triggers different cellular responses injury, including microglia eliminate debris recruit cells from circulation. Therapeutical options for IRDs currently limited, although small number patients have been successfully treated gene therapy. Many other therapeutic strategies being pursued mitigate deleterious effects associated with oxidative metabolism and/or inflammation, inhibiting reactive oxygen species’ accumulation responses, blocking autophagy. Several compounds tested clinical trials, generating great expectations their implementation. present review discusses main mechanisms that occur latest therapies under investigation.

Language: Английский

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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

PLoS ONE, Journal Year: 2019, Volume and Issue: 14(12), P. e0226197 - e0226197

Published: Dec. 10, 2019

Background Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and light entrainment of body’s circadian rhythms through their connection to pretectal nucleus hypothalamus, respectively. Increased awareness rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led a wave research focusing on role mRGCs these diseases. Postmortem analyses AD patients demonstrated significant loss mRGCs, vivo measurements mRGC function with chromatic pupillometry may be potential biomarker for early diagnosis progression AD. Methods We performed prospective case-control study 20 cognitively healthy participants: 10 individuals pre-symptomatic pathology (pre-AD), identified by presence abnormal levels amyloid β42 total Tau proteins cerebrospinal fluid, age-matched controls normal CSF levels. To evaluate function, we used standardized protocol Ganzfeld system using red (640 nm) blue (450 stimuli measured pupillary (PLR). Non-invasive wrist actigraphy sleep questionnaires were also completed rest-activity rhythm. Results Our results did not demonstrate difference PLR between pre-AD but showed variability group compared pupillometry. Wrist variable sleep-wake patterns irregular controls. Conclusions The seen cycle suggests that occurs stages, preceding cognitive decline. Future longitudinal studies following participants can help elucidating relationship

Language: Английский

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Circadian alterations in patients with neurodegenerative diseases: Neuropathological basis of underlying network mechanisms

Neurobiology of Disease, Journal Year: 2020, Volume and Issue: 144, P. 105029 - 105029

Published: July 28, 2020

Circadian organization of physiology and behavior is an important biological process that allows organisms to anticipate prepare for daily changes demands. Disruptions in this system precipitates a wide range health issues. In patients with neurodegenerative diseases, alterations circadian rhythms are among the most common debilitating symptoms. Although growing awareness these symptoms has occurred during last decade, their underlying neuropathophysiological circuitry remains poorly understood consequently no effective therapeutic strategies available alleviate Recent studies have examined neuropathological status different neural components governing generation diseases. review, we will dissect potential contribution dysfunctions nodes A deeper understanding mechanisms provide not only better disease neuro-pathophysiology, but also hold promise developing mechanisms-based therapies.

Language: Английский

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The Evolution-Driven Signature of Parkinson’s Disease

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(7), P. 475 - 492

Published: June 1, 2020

Evolutionarily based cellular vulnerability can explain clinical and pathological involvement of various structures in Parkinson's disease (PD).Neurons PD-prone share similar features, including long highly branched axons, spontaneous pacemaker spiking, elevated mitochondrial oxidant stress. In humans, the metabolic demands these cells are higher than other species, due to human longevity exceptionally large number synapses per neuron.Neurons displaying PD strikingly phenotypes across brain beyond substantia nigra pars compacta, dorsal vagal motor nucleus, amygdala, locus coeruleus, pedunculopontine raphe nuclei, diverse skin, retinal or heart autonomic ganglia.These remain largely unchanged throughout evolution, there is a mismatch between their relatively evolutionary conservation marked expansion telencephalon.In PD, numerous repercussions: gait automatization subconscious blindsight compromised; imprecise neuromodulatory tuning leads emotional, autonomic, sleep–wake dysregulation; ontogenetically primitive behaviours such as rapid eye movement sleep behaviour disorder re-emerge.Our model bridges from hierarchical concepts evolutionarily driven connectomics accounts for variability synchronicity symptoms anatomically separated networks. this review, we approach (PD) context an central nervous system functions. The neurons at risk have hyperbranched extensive transmitter release sites, display They function networks vertebrate but now connecting expanded cortex. Their breakdown favoured by longevity. At level, dysfunction starts synapses, then involves axons cell bodies. behavioural network dysfunctions provoke core syndrome parkinsonism freezing failed automatization, non-motor deficits inactive dysregulation. proposed re-interpretation prototypical allows new conceptual framework future research. second most frequent neurodegenerative humans. Age principal factor, with incidence rising exponentially above 60 years [1.de Lau L.M. Breteler M.M. Epidemiology disease.Lancet Neurol. 2006; 5: 525-535Abstract Full Text PDF PubMed Scopus (2087) Google Scholar]. previous Personal View paper, reviewed anatomical physiological differences PD-susceptible counterparts mammals [2.Diederich N.J. et al.Parkinson's disease: it consequence evolution?.Mov. Disord. 2019; 34: 453-459Crossref (5) first explore reasons focal certain types. A unifying pattern high energy multiple levels crystallizes, on salient studies that will be discussed detail. We extend review commonly accepted focus dopaminergic showing also serotonergic, cholinergic, noradrenergic neurons, all originating brainstem basal ganglia (BG). With novel approach, link vulnerable within argument related works comparative anatomy neurology. input sciences, re-interpret key syndromes manifestations dysfunctional maladaptive archaic argue modulate automated response environmental challenges, give examples supporting hypothesis. However, draw attention fact available literature does not symptoms, especially when comes those appearing lately course disease. As arguments develop, hope cement concept may dichotomy areas (specifically telencephalon) where numbers complexity increased markedly remained static terms indices. These data closely linked selective types rooting syndromes. 1997, Parent [3.Parent A. evolution involution.Biochem. Cell Biol. 1997; 75: 651-667Crossref Scholar] stated 'structures appear early among undergo involution ageing diseases' 'the processes play specifically target phylogenetically ancient components brain, SN.' But how? Based immunohistochemical findings, co-workers suspected characteristics axon understanding degenerative process [4.Parent al.Organization ganglia: importance axonal collateralization.Trends Neurosci. 2000; 23: 20-27Abstract Indeed, compacta (SNc) projections terminal regions extraordinary synaptic sites. For one neuron reaching out striatum has been estimated 1 × 106 2.4 106, highest values lateral part SNc [5.Bolam J.P. Pissadaki E.K. Living edge too many mouths feed: why dopamine die?.Mov. 2012; 27: 1478-1483Crossref (0) Scholar, 6.Redgrave P. al.Goal-directed habitual control implications disease.Nat. Rev. 2010; 11: 760-772Crossref (523) 7.Hernandez L.F. al.Dopaminergic Parkinson cost humans' performance.Trends 42: 375-383Abstract order maintain connections, develop degree arborization: they become hyperbranched. Although suggest primarily unfavourable ratio striatal suprastriatal cortical could hyperbranchism well single form goes up secondary, compensatory way succumb old age. Anyhow, potential propagation increases [8.Pissadaki Bolam action neurons: clues susceptibility disease.Front. Comput. 2013; 7: 13Crossref (124) (Figure 1). When taking into account length (DA) exceeds 4 m, instantly obvious bioenergetic associated abundant vesicular likely daunting [9.Attwell D. Laughlin S.B. An budget signaling grey matter brain.J. Cereb. Blood Flow Metab. 2011; 21: 1133-1145Crossref (1690) Scholar,10.Sengupta B. al.Information efficiency – synthesis.PLoS 9e1003157Crossref Other thousands sites telencephalic targets, although quantitative estimations case currently lacking. instance, serotonergic nuclei innervate forebrain [11.Deneris E. Gaspar Serotonin development: shaping molecular structural identities.Wiley Interdiscip. Dev. 2018; 7https://doi.org/10.1002/wdev.301Crossref (24) Pedunculopontine cholinergic coeruleus hypothalamic orexin long, telencephalon (see [12.Uchihara T. al.Propagation Aβ, tau α-synuclein pathology experimental models reality: prions, propagons propaganda.Acta Neuropathol. 2016; 131: 1-3Crossref (9) 13.Mena-Segovia J. Rethinking nucleus: organization function.Neuron. 2017; 94: 7-18Abstract (57) 14.Uchihara Giasson B.I. Propagation alpha-synuclein pathology: hypotheses, discoveries, yet unresolved questions studies.Acta 49-73Crossref (74) 15.Parent M. Relationship collateralization neuronal degeneration ganglia.J. Neural Transm. Suppl. 70: 85-88Google 16.Visser A.K. al.Measuring serotonin synthesis: conventional methods PET tracers (pre)clinical implications.Eur. Nucl. Med. Mol. Imaging. 38: 576-591Crossref Figure 2). Of note, well-conserved melanopsin-containing ganglion retina widely structures, only primary suprachiasmatic nucleus superior colliculus (SC) geniculate [17.Berson D.M. al.Phototransduction set circadian clock.Science. 2002; 295: 1070-1073Crossref (2051) Scholar,18.Hattar S. al.Melanopsin-containing cells: architecture, projections, intrinsic photosensitivity.Science. 1065-1070Crossref (1606) Beyond undeniable challenge, questioned how subtle gauging calibration maintained systems precise feedback should function. Adequate seems life, no more clinically confirmed less adequate movements, emotional expressions, reactions [19.Bowers al.Startling facts about emotion blunted reactivity aversive stimuli.Brain. 129: 3356-3365Crossref (79) While efficiently adaptive development, hyperbranching age, causing reversion slower, coarser, behaviours, characteristic features Box contributing, deleterious mechanisms).Figure 2Hyperbranchism Different Neuronal Networks Risk Involvement Disease (PD).Show full caption(A) Wide-ranging arborization GPi (from [15.Parent Scholar], permission). arrow points location body. estimation varicosities indicated parentheses. Reconstruction serial sections. (B) Melanopsin [31.Lax al.Photosensitive health rhythms.Int. Sci. 20E3164Crossref (4) left representative drawings illustrate melanopsin plexus subject, whereas right show (reduced) patient. Individual shown different colours. (C) connectivity (PPN) [13.Mena-Segovia Single-cell tracing depicted part. PPN represented shaded area. main three trajectories ascending stream, ventral descending projection. (D) Schematic [16.Visser Both autoreceptors (5-HT1A 5-HT1B) heteroreceptors postsynaptic receptors Abbreviations: Amyg, amygdala; Ant, anterior thalamus; CL, centrolateral thalamic nucleus; CM, centre median FH, Forel field H; GiN, gigantocellular GPi, internal segment globus pallidus; IC, inferior colliculus; PF, parafascicular Pf, PnC, pontis caudalis; PnO, oralis; PPN, tegmental RRA, retrorubral area; Rt, reticular SC, SNc, compacta; SNr, reticulata; STN, subthalamic VA/VL, anterior/ventral nuclei; VM, ventromedial VTA, area.View Large Image ViewerDownload Hi-res image Download (PPT)Box 1PD Deleterious Evolutionary MechanismsExaptation Utensil Network AdaptationEvolution progressed 'recycling' older circuits jobs. perspective BGs undergone what called 'exaptation'. This 'ancestral unit co-opted functions'. By changing output loops simultaneously modalities impact functions [72.Grillner Manira A.E. Current principles control, special reference locomotion.Physiol. 2020; 100: 271-320Crossref (12) One thus handles cognitive, parallel, despite increasing information input. Can exaptation increase process? Does lead genetic mutations toxins? particular, 'frequent reliance performance' [7.Hernandez strain systems?Antagonistic PleiotropyAntagonistic pleiotropy cognitive decline age [156.Magalhães Sandberg Cognitive aging extension linking learning, plasticity, neurodegeneration.Mech. Ageing 2005; 126: 1026-1033Crossref (32) phenotype status, during young succumbs later on. service larger territories, able transitorily permanently compensate producing amounts than, mouse [157.Burbulla al.Dopamine oxidation mediates lysosomal disease.Science. 357: 1255-1261Crossref (199) Later on, same mechanism enhances human-specific time-dependent cascade starting stress resulting, others, aSyn accumulation Scholar].Evolutionarily Imposed Trade-offsFar outreaching, energy-greedy optimal development late life. dilemma crisply described 'a tangle trade-offs: versus function' [158.Maklakov A.A. Chapman Evolution function.Proc. 286: 20191604Crossref (7) enormous: 2% body volume consumes 20% energy, requiring portion Among trade-offs posited telencephalization 'expensive tissue' hypothesis popular, proposes trade-off size digestive tract, which considerably smaller primate [159.Aiello L.C. Wheeler expensive-tissue hypothesis: evolution.Curr. Anthropol. 1995; 36: 199-221Crossref Scholar,160.Navarrete al.Energetics size.Nature. 480: 91-93Crossref Despite better digestibility current food, places burden enteric neurons. functional directly challenge BG. them, bipedal locomotion mentioned. comparing quadrupedal walking chimpanzees, bipedalism 75% costly attributable hip hindlimb [161.Sockol M.D. al.Chimpanzee locomotor energetics origin bipedalism.Proc. Natl. Acad. U. 2007; 104: 12265-12269Crossref (181) BG organizational coordinating forward locomotion. (A) Exaptation Adaptation systems? Antagonistic Pleiotropy Trade-offs Far Examination somatodendritic region at-risk gives additional insight factors might drive vulnerability. tier slow, autonomous pacemakers broad potentials oscillations cytosolic Ca2+ concentration [20.Surmeier D.J. modulation disease.Curr. Opin. Neurobiol. 2014; 29: 109-117Crossref (62) Scholar,21.Surmeier simply prion disorder.J. 37: 9799-9807Crossref (66) facilitating pacemaking process, oxidative phosphorylation ATP production, loading juxtaposed mitochondria Ca2+. feed-forward appears old, present muscle [22.Balaban R.S. Domestication cardiac mitochondrion conversion.J. Cell. Cardiol. 2009; 46: 832-841Abstract (61) ensures sustained synaptically activity fail because depletion. critical even short periods inactivity would cause suppression ongoing goal-directed possibly dire consequences organism's survival. Similarly, noninterrupted crucial systems, maintaining rhythms, preparedness arousal changes, fight flee responses active avoidance Scholar,23.Hormigo al.Circuits mediate expression signalled converge tegmentum.J. 39: 4576-4594Crossref cost, however, induced diminishes Complex I damage mitophagy [24.Grünewald al.Mitochondrial DNA depletion respiratory chain-deficient neurons.Ann. 79: 366-378Crossref tipping point, PD-vulnerable (at sites) go over 'cliff', senescent, die. context, mentioned healthy condition rate already near maximal sustainable actively involved located extended arborizations

Language: Английский

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Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle

Current Neuropharmacology, Journal Year: 2020, Volume and Issue: 19(2), P. 248 - 264

Published: April 29, 2020

All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous clocks are modulated by various pathways that essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new of timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics signaling clock have been identified. The physiology is expansive, its link neurodegeneration multifactorial. Circadian disruption prevelant contamporary society where light-noise, shift-work, transmeridian travel commonplace, also reported from early stages Alzheimer's disease (AD). alignment bright light therapy conjunction with chronobiotics beneficial treating sundowning syndrome other cognitive symptoms advanced AD patients. We performed a comprehensive analysis clinical reports review clock, delineate dysfunction AD, unravel dynamics vicious cycle between two pathologies. delineates role putative targets like proteins PER, CLOCK, BMAL1, ROR, clock-controlled AVP, SIRT1, FOXO, PK2 towards future approaches management AD. Furthermore, aging delineated.

Language: Английский

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