Reversibility of visual field defects through induction of brain plasticity: vision restoration, recovery and rehabilitation using alternating current stimulation

For decades visual field defects were considered irreversible because it was thought that in the visual system the regeneration potential of the neuronal tissues is low.Nevertheless,there is always some potential for partial recovery of the visual field defect that can be achieved through induction of neuroplasticity.Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy.It is maintained throughout life and just as neurological rehabilitation can improve motor coordination,visual field defects in glaucoma,diabetic retinopathy or optic neuropathy can be improved by inducing neuroplasticity.In ophthalmology many new treatment paradigms have been tested that can induce neuroplastic changes,including non-invasive alternating current stimulation.Treatment with alternating current stimulation(e.g.,30 minutes,daily for 10 days using transorbital electrodes and^10 Hz)activates the entire retina and parts of the brain.Electroencephalography and functional magnetic resonance imaging studies revealed local activation of the visual cortex,global reorganization of functional brain networks,and enhanced blood flow,which together activate neurons and their networks.The future of low vision is optimistic because vision loss is indeed,partially reversible.

Associations between meeting 24-hour movement guidelines and quality of life among children and adolescents with autism spectrum disorder

Background:The Canadian 24-hour movement behavior(24-HMB)guidelines suggest that a limited amount of screen time use,an adequate level of physical activity(PA),and sufficient sleep duration are beneficial for ensuring and optimizing the health and quality of life(QoL)of children and adolescents.However,this topic has yet to be examined for children and adolescents with autism spectrum disorder(ASD)specifically.The aim of this cross-sectional observational study was to examine the associations between meeting 24-HMB guidelines and several QoLrelated indicators among a national sample of American children and adolescents with ASD.Methods:Data were taken from the 2020 U.S.National Survey of Children’s Health dataset.Participants(n=956)aged 617 years and currently diagnosed with ASD were included.The exposure of interest was adherence to the 24-HMB guidelines.Outcomes were QoL indicators,including learning interest/curiosity,repeating grades,adaptive ability,victimization by bullying,and behavioral problems.Categorical variables were described with unweighted sample counts and weighted percentages.Age,sex,race,preterm birth status,medication,behavioral treatment,household poverty level,and the educational level of the primary caregivers were included as covariates.Odds ratio(OR)and 95%confidence interval(95%CI)were used to present the strength of association between adherence to 24-HMB guidelines and QoL-related indicators.Results:Overall,452 participants(45.34%)met 1 of the 3 recommendations,216(22.65%)met 2 recommendations,whereas only 39 participants(5.04%)met all 3 recommendations.Compared with meeting none of the recommendations,meeting both sleep duration and PA recommendations(OR=3.92,95%CI:1.639.48,p<0.001)or all 3 recommendations(OR=2.11,95%CI:1.034.35,p=0.04)was associated with higher odds of showing learning interest/curiosity.Meeting both screen time and PA recommendations(OR=0.15,95%CI:0.040.61,p<0.05)or both sleep duration and PA recommendations(OR=0.24,95%CI:0.070.87,p<0.05)was associated with lower odds of repeating any grades.With respect to adaptive ability,participants who met only the PA recommendation of the 24-HMB were less likely to have difficulties dressing or bathing(OR=0.11,95%CI:0.020.66,p<0.05)than those who did not.For participants who met all 3 recommendations(OR=0.38,95%CI:0.150.99,p=0.05),the odds of being victimized by bullying was lower.Participants who adhered to both sleep duration and PA recommendations were less likely to present with severe behavioral problems(OR=0.17,95%CI:0.040.71,p<0.05)than those who did not meet those guidelines.Conclusion:Significant associations were found between adhering to 24-HMB guidelines and selected QoL indicators.These findings highlight the importance of maintaining a healthy lifestyle as a key factor in promoting and preserving the QoL of children with ASD.

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage

Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).

The role of microglia versus peripheral macrophages in maladaptive plasticity after nerve injury

Microglia and macrophages in the development of maladaptive plastic changes after peripheral nerve injury:Microglia and macrophages encompass the innate immune response to injury in the central and peripheral nervous systems,respectively,and are intimately involved in the pathogenesis of maladaptive changes(Tsuda,2019).These dynamic cells can influence neuronal activity in active and quiescent states.Conflicting findings argue that peripheral macrophages facilitate the development of nerve injury-induced neuropathic pain,as opposed to central microglia(Lopes et al.,2017;Yu et al.,2020).

青少年应激引起腹侧海马长时程增强的持续增加：星形细胞谷氨酰胺合成酶的作用

童年期创伤是引发与压力有关的精神病的最重要风险因素之一,例如创伤后压力障碍或抑郁。尽管已证实星形胶质细胞在调节递质释放和突触可塑性中发挥作用,然而目前尚不清楚星形胶质递质代谢在这种应激诱导的精神病理学中所起的作用。在啮齿动物,可以通过青少年应激暴露来模拟童年逆境,从而导致焦虑加剧以及成年后应对压力的能力下降。我们描述了这种幼年应激大鼠,无论成年期是否有其他应激,都会导致腹侧CA1(v CA1)Schaffer侧支的突触效力降低,而高频刺激后突触传递的长时程增强(LTP)增加。我们通过阻断星形胶质谷氨酸降解酶谷氨酰胺合成酶(GS)测试谷氨酸-谷氨酰胺循环是否引起青少年应激后可塑性的持久变化。用蛋氨酸亚砜亚胺对正常大鼠的切片中GS的药理抑制的确模仿青少年应激对vCA1-LTP的影响,而提供谷氨酰胺足以使LTP正常化。评估在青少年、成年期或青少年/成年联合应激后,vCA1辐射层中的稳态mRNA水平揭示了GS、星形细胞谷氨酸和谷氨酰胺转运蛋白表达的明显变化。尽管青少年应激后GS mRNA表达水平持续降低,但GS蛋白水平保持稳定。本研究结果表明,星形胶质细胞和谷氨酸-谷氨酰胺循环在介导青少年应激对vCA1(与焦虑和情绪记忆处理有关的区域)的可塑性的长期影响中起关键作用。

Utilizing multiphoton imaging and integrative clearing to reveal sex differences in neuroimmune interactions after nerve injury

With the constant development of multiphoton microscopy,our ability to observe complex and dynamic biological processes deeper within living tissue,is steadily improving.Researchers use multiphoton microscopy,because experiments can be conducted with little to no invasiveness or tissue damage over a long period of time with no photodamage(Mancuso et al.,2009).This allows for the introduction of tissue into the context of a three-dimensional 3D environment in which visualization of cellular activation and interaction is viable.By circumventing a distorted reconstruction with limited z-stacks,multiphoton imaging provides enhanced spatiotemporal resolution.

Parkinson’s Disease: Examining the Role of the Pedunculopontine Nucleus via Animal Models

Parkinson’s disease is a neurodegenerative disease that spreads rapidly through the brain, and can influence a number of vital systems. The cause of this disease appears to be brought on by the progressive inability to produce adequate dopamine in the brain. People that suffer with Parkinson’s have reported REM sleep disruption at the onset of the condition. This paper reviews several animal model lesion studies related to the Pedunculopontine Nucleus, and how it plays a role in sleep regulation following a decline in dopamine production in those with parkinsonian conditions. The goal of this paper is to elucidate the functioning of the PPN and explain the nuclei’s possible role in the onset and progression of parkinsonian conditions in animal models.

High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal networks.An ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain areas.Recently introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging tool.Compared to endoscopes based on graded-index lenses or fibre bundles,this new approach offers a footprint reduction exceeding an order of magnitude,combined with a significant enhancement in resolution.We designed a compact and high-speed system for fluorescent imaging at the tip of a fibre,achieving a resolution of 1.18±0.04μm across a 50-μm field of view,yielding 7-kilopixel images at a rate of 3.5 frames/s.Furthermore,we demonstrate in vivo observations of cell bodies and processes of inhibitory neurons within deep layers of the visual cortex and hippocampus of anaesthetised mice.This study paves the way for modern microscopy to be applied deep inside tissues of living animal models while exerting a minimal impact on their structural and functional properties.

儿童观看卡通片激活内侧前额皮层

成人的内侧前额叶皮层(medial prefrontal cortex,MPFC)参与加工真实人物而非虚拟人造角色的心理活动.与成人相比,儿童更加迷恋卡通形象,本文研究儿童的MPFC活动是否也能区分加工真实人物和虚拟人造角色的心理活动.通过功能磁共振成像(functional magnetic resonance imaging,fMRI)测量10岁儿童观看电影和卡通片段时候的大脑激活情况,其中电影和卡通分别代表真实和虚拟生活场景.结果发现,与成人不同,儿童的MPFC在观看描述类似事件的真实人物和虚拟角色的时候都会被激活.这些结果表明,10岁左右的儿童观看虚拟现实中的人造角色时,其MPFC可以被自动激活,这与成人的MPFC活动不同.

Watching cartoons activates the medial prefrontal cortex in children

The medial prefrontal cortex (MPFC) of human adults is involved in attributing mental states to real human agents but not to virtual artificial characters. This study examined whether such differential MPFC activity can be observed in children who are more fascinated by cartoons than adults. We measured brain activity using functional magnetic resonance imaging (fMRI) while 10-year-old children watched movie and cartoon clips, simulating real and virtual visual worlds, respectively. We showed neuroimaging evidence that, in contrast to adults, the MPFC of children was activated when perceiving both human agents and artificial characters in coherent visual events. Our findings suggest that, around the age of 10 years, the MPFC activity in children is different from that in adults in that it can be spontaneously activated by non-human agents in a virtual visual world.

Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance,neuroinflammation and Alzheimer’s disease

Background:The metabolic syndrome is a consequence of modern lifestyle that causes synaptic insulin resistance and cognitive deficits and that in interaction with a high amyloid load is an important risk factor for Alzheimer’s dis-ease.It has been proposed that neuroinflammation might be an intervening variable,but the underlying mechanisms are currently unknown.Methods:We utilized primary neurons to induce synaptic insulin resistance as well as a mouse model of high-risk aging that includes a high amyloid load,neuroinflammation,and diet-induced obesity to test hypotheses on underly-ing mechanisms.Results:We found that neddylation and subsequent activation of cullin-RING ligase complexes induced synaptic insulin resistance through ubiquitylation and degradation of the insulin-receptor substrate IRS1 that organizes synap-tic insulin signaling.Accordingly,inhibition of neddylation preserved synaptic insulin signaling and rescued memory deficits in mice with a high amyloid load,which were fed with a’western diet’.Conclusions:Collectively,the data suggest that neddylation and degradation of the insulin-receptor substrate is a nodal point that links high amyloid load,neuroinflammation,and synaptic insulin resistance to cognitive decline and impaired synaptic plasticity in high-risk aging.

Structure of serotonin receptors:molecular underpinning of receptor activation and modulation

The structural basis of the regulation of serotonin(5-hydroxy-tryptamine,5-HT)receptors by ligands and lipids is only emerging.A recent study by Xu and colleagues1 published in Nature addresses this issue by resolving five structures of 5-HT;receptor-G protein complexes.These include 5-HT1A in the apostate,i.e.not bound to a ligand,5-HT1A and 5-HT1D bound to serotonin or the atypical antipsychotic aripiprazole(for 5-HT1A),and 5-HT1E bound to its selective agonist BRL-54443.