scholarly journals Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlo N. G. Giachello ◽  
Yuen Ngan Fan ◽  
Matthias Landgraf ◽  
Richard A. Baines
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Critical Period ◽  
System Development ◽  
Nervous System Development ◽  
Critical Periods ◽  
Locomotor System ◽  
Network Function ◽  
Synaptic Excitation ◽  
No Signaling

AbstractThe emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network.

scholarly journals Activity manipulation of an excitatory interneuron, during an embryonic critical period, alters network tuning of the Drosophila larval locomotor circuit

2019 ◽  
Author(s):  
Carlo N. G. Giachello ◽  
Yuen Ngan Fan ◽  
Matthias Landgraf ◽  
Richard A. Baines
Keyword(s):  
Nitric Oxide ◽  
Critical Period ◽  
Critical Periods ◽  
Nervous Systems ◽  
Network Function ◽  
Network Response ◽  
Mechanistic Insight ◽  
Potential Mediator ◽  
Activity State ◽  
Activity Dependent

AbstractAs nervous systems develop, activity perturbations during critical periods can lead to permanently altered network function. However, how activity perturbation influences individual synapses, the network response and the underlying signalling mechanisms are not well understood. Here, we exploit a recently identified critical period in the development of the Drosophila larval locomotor circuit to show that activity perturbation differentially affects individual and identified synaptic pairings. Remarkably, we further show that activity-manipulation of a selective excitatory interneuron is sufficient to fully recapitulate the effects induced by network-wide activity disturbance; indicative that some neurons make a greater contribution to network tuning. We identify nitric oxide (NO)-signalling as a potential mediator of activity-dependent network tuning during the critical period. Significantly, the effect of NO-signalling to network tuning is dictated by the prior activity state of the network. Thus, this study provides mechanistic insight that is currently lacking into how activity during a critical period tunes a developing network.

Endocannabinoid signals in the developmental programming of delayed-onset neuropsychiatric and metabolic illnesses

2013 ◽  
Vol 41 (6) ◽  
pp. 1569-1576 ◽  
Author(s):  
Erik Keimpema ◽  
Daniela Calvigioni ◽  
Tibor Harkany
Keyword(s):  
Prescription Drugs ◽  
Maternal Nutrition ◽  
System Development ◽  
Nervous System Development ◽  
Molecular Evidence ◽  
Critical Periods ◽  
Affected Offspring ◽  
Neuropsychiatric Diseases ◽  
Maternal Programming ◽  
And Function

It is increasingly recognized that maternal exposure to metabolic (nutritional) stimuli, infections, illicit or prescription drugs and environmental stressors during pregnancy can predispose affected offspring to developing devastating postnatal illnesses. If detrimental maternal stimuli coincide with critical periods of tissue production and organogenesis then they can permanently derail key cellular differentiation programs. Maternal programming can thus either provoke developmental failure directly (‘direct hit’) or introduce latent developmental errors that enable otherwise sub-threshold secondary stressors to manifest as disease (‘double hit’) postnatally. Accumulating evidence suggests that nervous system development is tightly controlled by maternal metabolic stimuli, and whose synaptic wiring and integrative capacity are adversely affected by dietary and hormonal challenges, infections or episodes of illicit drug use. Endocannabinoids, a family of signal lipids derived from polyunsaturated fatty acids, have been implicated in neuronal fate determination, the control of axonal growth, synaptogenesis and synaptic neurotransmission. Therefore the continuum and interdependence of endocannabinoid actions during the formation and function of synapses together with dynamic changes in focal and circulating endocannabinoid levels upon maternal nutritional imbalance suggest that endocannabinoids can execute the ‘reprogramming’ of specific neuronal networks. In the present paper, we review molecular evidence suggesting that maternal nutrition and metabolism during pregnancy can affect the formation and function of the hippocampus and hypothalamus by altering endocannabinoid signalling such that neuropsychiatric diseases and obesity respectively ensue in affected offspring. Moreover, we propose that the placenta, fetal adipose and nervous tissues interact via endocannabinoid signals. Thus endocannabinoids are hypothesized to act as a molecular substrate of maternal programming.

Maria Montessori and Neuroscience: The Trailblazing Insights of an Exceptional Mind

2020 ◽  
Vol 26 (5-6) ◽  
pp. 394-401
Author(s):  
Mara Fabri ◽  
Stefania Fortuna
Keyword(s):  
System Development ◽  
Vital Role ◽  
Nervous System Development ◽  
Critical Periods ◽  
Neural Structure ◽  
Neuropsychological Development ◽  
Maria Montessori ◽  
Neuroscience Research ◽  
Child Centered

This comment presents Maria Montessori (1870–1952) and highlights that her child-centered method of education is based on brilliant intuitions, which were confirmed by neuroscience research many decades later, such as the distinction of three critical periods in children’s psychobiological development; the importance of the environment in supporting cerebral development and in promoting learning, as well as of affective stimulation in psychological growth and maturation; the specific neural structure of humans that specifically enables the acquisition of a language; the vital role of fine object manipulation in neuropsychological development, and of the physical exercise in brain and nervous system development.

The effect of folic acid as an antioxidant on the hypothalamic monoamines in experimentally induced hypothyroid rat

2011 ◽  
Vol 28 (3) ◽  
pp. 253-261 ◽  
Author(s):  
Wafaa Ibrahim ◽  
Ehab Tousson ◽  
Thanaa El-Masry ◽  
Nadia Arafa ◽  
Mohamed Akela
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Folic Acid ◽  
Group Treatment ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Control Group ◽  
Albino Rats ◽  
Pubertal Stage

Thyroid hormones are recognized as key metabolic hormones that play a critical role in the central nervous system development throughout life. In the present study, we studied the biochemical changes of hypothalamus of hypothyroid rats at post-pubertal stage, and the possible ameliorating effect of folic acid. A total of 50 male albino rats were equally divided into five groups; the first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which rats received daily 6- n-propyl-2-thiouracil (PTU) in drinking water for 6 weeks to induce hypothyroidism. The fourth and fifth groups were hypothyroid rats treated with folic acid for 4 weeks during and after receiving PTU, respectively, and were dissected after 6 and 10 weeks, respectively. There was a significant increase in plasma total homocysteine, malondialdehyde (MDA), oxidized glutathione\reduced glutathione and total nitric oxide and hypothalamic MDA, serotonin and norepinephrine in the hypothyroid rats group as compared to the control group. This reflects hyperhomocysteinaemia and oxidative stress associated with hypothyroid state. On the other hand, hypothalamic total nitric oxide and dopamine in the hypothyroid rats group were significantly decreased when compared to the control group. Treatment of hypothyroid rats with folic acid improves the oxidative stress and hypothalamic monoamines. Our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state.

scholarly journals An Overview of Studies Demonstrating that ex vivo Neuronal Networks Display Multiple Complex Behaviors: Emergent Properties of Nearest-Neighbor Interactions of Excitatory and Inhibitory Neurons.

2021 ◽  
Vol 15 (1) ◽  
pp. 3-15
Author(s):  
Thomas B. Shea
Keyword(s):  
Nervous System ◽  
Neuronal Activity ◽  
Neuronal Networks ◽  
Ex Vivo ◽  
System Development ◽  
Higher Order ◽  
Nervous System Development ◽  
Electrode Arrays ◽  
Higher Order Functions

The responsiveness of the human nervous system ranges from the basic sensory interpretation and motor regulation to so-called higher-order functions such as emotion and consciousness. Aspects of higher-order functions are displayed by other mammals and birds. In efforts to understand how neuronal interaction can generate such a diverse functionality, murine embryonic cortical neurons were cultured on Petri dishes containing multi-electrode arrays that allowed recording and stimulation of neuronal activity. Despite the lack of major architectural features that govern nervous system development in situ, this overview of multiple studies demonstrated that these 2-dimensional ex vivo neuronal networks nevertheless recapitulate multiple key aspects of nervous system development and activity in situ, including density-dependent, the spontaneous establishment of a functional network that displayed complex signaling patterns, and responsiveness to environmental stimulation including generation of appropriate motor output and long-term potentiation. These findings underscore that the basic interplay of excitatory and inhibitory neuronal activity underlies all aspects of nervous system functionality. This reductionist system may be useful for further examination of neuronal function under developmental, homeostatic, and neurodegenerative conditions.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li
Keyword(s):  
Brain Damage ◽  
Intracellular Signaling ◽  
System Development ◽  
Intrauterine Infection ◽  
Artery Occlusion ◽  
Nervous System Development ◽  
Human Infants ◽  
Hypoxic Ischemia ◽  
Show Evidence ◽  
The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

Antenatal Glucocorticoids Supplementation and Central Nervous System Development

2013 ◽  
Vol 14 (2) ◽  
pp. 160-166
Author(s):  
Diego Gazzolo ◽  
Laura D. Serpero ◽  
Alessandro Frigiola ◽  
Raul Abella ◽  
Alessandro Giamberti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Central Nervous System Development

Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review

2020 ◽  
Vol 20 (17) ◽  
pp. 1781-1790
Author(s):  
Noor Anisah Abu Yazit ◽  
Norsham Juliana ◽  
Srijit Das ◽  
Nur Islami Mohd Fahmi Teng ◽  
Nadia Mohd Fahmy ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Chromosomal Abnormalities ◽  
Current Knowledge ◽  
System Development ◽  
Genetic Disorder ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Importance ◽  
Nervous System Development ◽  
Micro Rna ◽  
A Genome

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.

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