scholarly journals Thalamocortical Afferents Innervate the Cortical Subplate much Earlier in Development in Primate than in Rodent

2019 ◽  
Vol 29 (4) ◽  
pp. 1706-1718 ◽  
Author(s):  
Ayman Alzu’bi ◽  
Jihane Homman-Ludiye ◽  
James A Bourne ◽  
Gavin J Clowry
Keyword(s):  
Cortical Neuron ◽  
Fetal Development ◽  
Cortical Neurons ◽  
Current Model ◽  
Internal Capsule ◽  
Ventral Telencephalon ◽  
Cortical Neurogenesis ◽  
Acetylcholinesterase Histochemistry ◽  
Dorsolateral Cortex ◽  
Early Human

Abstract The current model, based on rodent data, proposes that thalamocortical afferents (TCA) innervate the subplate towards the end of cortical neurogenesis. This implies that the laminar identity of cortical neurons is specified by intrinsic instructions rather than information of thalamic origin. In order to determine whether this mechanism is conserved in the primates, we examined the growth of thalamocortical (TCA) and corticofugal afferents in early human and monkey fetal development. In the human, TCA, identified by secretagogin, calbindin, and ROBO1 immunoreactivity, were observed in the internal capsule of the ventral telencephalon as early as 7–7.5 PCW, crossing the pallial/subpallial boundary (PSB) by 8 PCW before the calretinin immunoreactive corticofugal fibers do. Furthermore, TCA were observed to be passing through the intermediate zone and innervating the presubplate of the dorsolateral cortex, and already by 10–12 PCW TCAs were occupying much of the cortex. Observations at equivalent stages in the marmoset confirmed that this pattern is conserved across primates. Therefore, our results demonstrate that in primates, TCAs innervate the cortical presubplate at earlier stages than previously demonstrated by acetylcholinesterase histochemistry, suggesting that pioneer thalamic afferents may contribute to early cortical circuitry that can participate in defining cortical neuron phenotypes.

Nrf2 mediates the neuroprotective effect of isoflurane preconditioning in cortical neuron injury induced by oxygen-glucose deprivation

2021 ◽  
pp. 096032712198941
Author(s):  
X-S Liu ◽  
X-L Bai ◽  
Z-X Wang ◽  
S-Y Xu ◽  
Y Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cortical Neuron ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Lactate Dehydrogenase Activity ◽  
Primary Mouse ◽  
Ldh Release ◽  
Neuron Injury ◽  
And Oxidative Stress

Objective: To investigate how nuclear factor-E2-related factor 2 (Nrf2) involved in the protective effect of isoflurane (Iso) preconditioning in oxygen glucose deprivation (OGD)-induced cortical neuron injury. Methods: Primary mouse cortical neurons were divided into Control, ML385 (an Nrf2 inhibitor), Iso, Iso + ML385, OGD, ML385 + OGD, Iso + OGD, and Iso + ML385 + OGD groups. Lactate dehydrogenase activity (LDH) release and oxidative stress indexes were quantified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability, Annexin V-FITC/propidium iodide (PI) staining to measure cell apoptosis, dichloro-dihydro-fluorescein diacetate (DCFH-DA) method to test reactive oxygen species (ROS), and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting to evaluate genes and protein expression. Results: Iso preconditioning reduced LDH release and inhibited cell cytotoxicity in OGD-induced cortical neurons, which was abolished by ML385. Iso preconditioning increased the Nrf2 nuclear translocation in cortical neurons. Meanwhile, Iso decreased the OGD-induced apoptosis with the down-regulations of Bax and Caspase-3 and the up-regulation of Bcl-2, which was reversed by ML385. OGD enhanced the level of ROS and malondialdehyde (MDA) in cortical neurons, but reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were aggravated in ML385 + OGD group and mitigated in Iso + OGD group. No observable difference was found between OGD group and Iso + ML385 + OGD group regarding apoptosis-related proteins and oxidative stress-related indexes. Conclusion: Iso preconditioning up-regulated Nrf2 level to play its protective role in OGD-induced mouse cortical neuron injury.

scholarly journals Analysis of Multiquantal Transmitter Release From Single Cultured Cortical Neuron Terminals

1999 ◽  
Vol 81 (4) ◽  
pp. 1810-1817 ◽  
Author(s):  
Oliver Prange ◽  
Timothy H. Murphy
Keyword(s):  
Cortical Neuron ◽  
Cortical Neurons ◽  
Transmitter Release ◽  
Primary Cultures ◽  
Three Dimensional ◽  
Variable Number ◽  
Release Process ◽  
Release Probability ◽  
Synaptic Terminals ◽  
Neuron Terminals

Analysis of multiquantal transmitter release from single cultured cortical neuron terminals. Application of single synapse recording methods indicates that the amplitude of postsynaptic responses of single CNS synapses can vary greatly among repeated stimuli. To determine whether this observation could be attributed to synapses releasing a variable number of transmitter quanta, we assessed the prevalence of multiquantal transmitter release in primary cultures of cortical neurons with the action potential (AP)-dependent presynaptic turnover of the styryl dye FM1–43 ( Betz and Bewick 1992 , 1993 ; Betz et al. 1996 ). It was assumed that if a high proportion of vesicles within a terminal were loaded with FM1–43 the amount of dye released per stimulus would be proportional to the number of quanta released and/or the probability of release at a terminal. To rule out differences in the amount of release (between terminals) caused by release probability or incomplete loading of terminals, conditions were chosen to maximize both release probability and terminal loading. Three-dimensional reconstruction of terminals was employed to ensure that bouton fluorescence was accurately measured. Analysis of the relationship between the loading of terminals and release indicated that presumed larger terminals (>FM1–43 uptake) release a greater amount of dye per stimulus than smaller terminals, suggesting multiquantal release. The distribution of release amounts across terminals was significantly skewed toward higher values, with 13–17% of synaptic terminals apparently releasing multiple quanta per AP. In conclusion, our data suggest that most synaptic terminals release a relatively constant amount of transmitter per stimulus; however, a subset of terminals releases amounts of FM1–43 that are greater than that expected from a unimodal release process.

scholarly journals Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by β-amyloid 31-35

2009 ◽  
Vol 102 (5) ◽  
pp. 655-662 ◽  
Author(s):  
Huan-Ling Yu ◽  
Li Li ◽  
Xiao-Hong Zhang ◽  
Li Xiang ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Cortical Neuron ◽  
Cortical Neurons ◽  
Tail Length ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Neuroprotective Effects ◽  
Regulated Expression ◽  
Cultured Cortical Neurons ◽  
Β Amyloid

Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in β-amyloid (Aβ) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Aβ31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

scholarly journals Length of the Neurogenic Period—A Key Determinant for the Generation of Upper-Layer Neurons During Neocortex Development and Evolution

2021 ◽  
Vol 9 ◽  
Author(s):  
Barbara K. Stepien ◽  
Samir Vaid ◽  
Wieland B. Huttner
Keyword(s):  
Cognitive Abilities ◽  
Cortical Neurons ◽  
Mammalian Species ◽  
Critical Role ◽  
Exact Nature ◽  
Cortical Neurogenesis ◽  
Brain Functions ◽  
The Relationship ◽  
Development And Evolution

The neocortex, a six-layer neuronal brain structure that arose during the evolution of, and is unique to, mammals, is the seat of higher order brain functions responsible for human cognitive abilities. Despite its recent evolutionary origin, it shows a striking variability in size and folding complexity even among closely related mammalian species. In most mammals, cortical neurogenesis occurs prenatally, and its length correlates with the length of gestation. The evolutionary expansion of the neocortex, notably in human, is associated with an increase in the number of neurons, particularly within its upper layers. Various mechanisms have been proposed and investigated to explain the evolutionary enlargement of the human neocortex, focussing in particular on changes pertaining to neural progenitor types and their division modes, driven in part by the emergence of human-specific genes with novel functions. These led to an amplification of the progenitor pool size, which affects the rate and timing of neuron production. In addition, in early theoretical studies, another mechanism of neocortex expansion was proposed—the lengthening of the neurogenic period. A critical role of neurogenic period length in determining neocortical neuron number was subsequently supported by mathematical modeling studies. Recently, we have provided experimental evidence in rodents directly supporting the mechanism of extending neurogenesis to specifically increase the number of upper-layer cortical neurons. Moreover, our study examined the relationship between cortical neurogenesis and gestation, linking the extension of the neurogenic period to the maternal environment. As the exact nature of factors promoting neurogenic period prolongation, as well as the generalization of this mechanism for evolutionary distinct lineages, remain elusive, the directions for future studies are outlined and discussed.

scholarly journals Muscone Exerts Neuroprotection in an Experimental Model of Stroke via Inhibition of the Fas Pathway

2012 ◽  
Vol 7 (8) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Gang Wei ◽  
Dong-Feng Chen ◽  
Xiao-Ping Lai ◽  
Dong-Hui Liu ◽  
Ru-Dong Deng ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cortical Neuron ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
Infarct Volume ◽  
Neurological Dysfunction ◽  
Gas Chromatography Mass Spectrometry ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Cell Viability Assay

Identifying small molecules that are neuroprotective against stroke injury will be highly beneficial for treatment therapies. A cell viability assay and gas chromatography-mass spectrometry were used to identify active small molecules in XingNaoJing, which is a well known Chinese Medicine prescribed for the effective treatment of stroke. Studies have found that muscone is the active compound that prevents PC12 cell and cortical neuron damage following various injuries. Analysis of apoptosis indicated that muscone inhibited glutamate-induced apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8 expression were upregulated following glutamate treatment in cortical neurons, and was markedly attenuated in the presence of muscone. Furthermore, muscone significantly reduced cerebral infarct volume, neurological dysfunction and inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO) rats in a dose-dependent manner. Moreover, a significant decrease in Fas and caspase-8 expression in the rat cortex was observed in MCAO rats treated with muscone. Our results demonstrate that muscone may be a small active molecule with neuroprotective properties, and that inhibition of apoptosis and Fas is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.

scholarly journals Trio Mediates Netrin-1-Induced Rac1 Activation in Axon Outgrowth and Guidance

2008 ◽  
Vol 28 (7) ◽  
pp. 2314-2323 ◽  
Author(s):  
Anne Briançon-Marjollet ◽  
Atefeh Ghogha ◽  
Homaira Nawabi ◽  
Ibtissem Triki ◽  
Camille Auziol ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Anterior Commissure ◽  
Internal Capsule ◽  
Axon Outgrowth ◽  
Nucleotide Exchange ◽  
Deleted In Colorectal Cancer ◽  
Commissural Axons ◽  
Guidance Cue ◽  
Axonal Projections ◽  
Nucleotide Exchange Factor

ABSTRACT The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. The guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 activation has not yet been identified. Here, we show that the RhoGEF Trio mediates Rac1 activation in netrin-1 signaling. We found that Trio interacts with the netrin-1 receptor DCC in mouse embryonic brains and that netrin-1-induced Rac1 activation in brain is impaired in the absence of Trio. Trio−/− cortical neurons fail to extend neurites in response to netrin-1, while they are able to respond to glutamate. Accordingly, netrin-1-induced commissural axon outgrowth is reduced in Trio−/− spinal cord explants, and the guidance of commissural axons toward the floor plate is affected by the absence of Trio. The anterior commissure is absent in Trio-null embryos, and netrin-1/DCC-dependent axonal projections that form the internal capsule and the corpus callosum are defective in the mutants. Taken together, these findings establish Trio as a GEF that mediates netrin-1 signaling in axon outgrowth and guidance through its ability to activate Rac1.

scholarly journals Dynein activating adaptor BICD2 controls radial migration of upper-layer cortical neurons in vivo

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Lena Will ◽  
Sybren Portegies ◽  
Jasper van Schelt ◽  
Merel van Luyk ◽  
Dick Jaarsma ◽  
...  
Keyword(s):  
Cortical Neuron ◽  
Cortical Neurons ◽  
Cortical Development ◽  
Adaptor Protein ◽  
Cortical Plate ◽  
Neuron Migration ◽  
Knock Out ◽  
Radial Migration

Abstract For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurological diseases, including malformations of cortical development. Previous studies have shown that knockdown of BICD2 interferes with interkinetic nuclear migration in radial glial progenitor cells, and that Bicd2-deficient mice display an altered laminar organization of the cerebellum and the neocortex. However, the precise in vivo role of BICD2 in neocortical development remains unclear. By comparing cell-type specific conditional Bicd2 knock-out mice, we found that radial migration in the cortex predominantly depends on BICD2 function in post-mitotic neurons. Neuron-specific Bicd2 cKO mice showed severely impaired radial migration of late-born upper-layer neurons. BICD2 depletion in cortical neurons interfered with proper Golgi organization, and neuronal maturation and survival of cortical plate neurons. Single-neuron labeling revealed a specific role of BICD2 in bipolar locomotion. Rescue experiments with wildtype and disease-related mutant BICD2 constructs revealed that a point-mutation in the RAB6/RANBP2-binding-domain, associated with cortical malformation in patients, fails to restore proper cortical neuron migration. Together, these findings demonstrate a novel, cell-intrinsic role of BICD2 in cortical neuron migration in vivo and provide new insights into BICD2-dependent dynein-mediated functions during cortical development.

scholarly journals ERK1/2 Antagonizes Glycogen Synthase Kinase-3β-induced Apoptosis in Cortical Neurons

2002 ◽  
Vol 277 (51) ◽  
pp. 49577-49584 ◽  
Author(s):  
Michal Hetman ◽  
Shih-Ling Hsuan ◽  
Agata Habas ◽  
Matthew J. Higgins ◽  
Zhengui Xia
Keyword(s):  
Cortical Neuron ◽  
Cortical Neurons ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Activation ◽  
Induced Apoptosis ◽  
Neuron Apoptosis ◽  
Constitutively Active

Inhibition of glycogen synthase kinase-3β (GSK3β) is one of the mechanisms by which phosphatidylinositol 3-kinase (PI3K) activation protects neurons from apoptosis. Here, we report that inhibition of ERK1/2 increased the basal activity of GSK3β in cortical neurons and that both ERK1/2 and PI3K were required for brain-derived neurotrophic factor (BDNF) suppression of GSK3β activity. Moreover, cortical neuron apoptosis induced by expression of recombinant GSK3β was inhibited by coexpression of constitutively active MKK1 or PI3K. Activation of both endogenous ERK1/2 and PI3K signaling pathways was required for BDNF to block apoptosis induced by expression of recombinant GSK3β. Furthermore, cortical neuron apoptosis induced by LY294002-mediated activation of endogenous GSK3β was blocked by expression of constitutively active MKK1 or by BDNF via stimulation of the endogenous ERK1/2 pathway. Although both PI3K and ERK1/2 inhibited GSK3β activity, neither had an effect on GSK3β phosphorylation at Tyr-216. Interestingly, PI3K (but not ERK1/2) induced the inhibitory phosphorylation of GSK3β at Ser-9. Significantly, coexpression of constitutively active MKK1 (but not PI3K) still suppressed neuronal apoptosis induced by expression of the GSK3β(S9A) mutant. These data suggest that activation of the ERK1/2 signaling pathway protects neurons from GSK3β-induced apoptosis and that inhibition of GSK3β may be a common target by which ERK1/2 and PI3K protect neurons from apoptosis. Furthermore, ERK1/2 inhibits GSK3β activity via a novel mechanism that is independent of Ser-9 phosphorylation and likely does not involve Tyr-216 phosphorylation.

scholarly journals The Effect of Intravenously and Intra-arterially Delivered Human Umbilical Cord Blood Mononuclear Cell on Cortical Neurogenesis of Post-Ischemic Stroke Rat Brain

2021 ◽  
Vol 9 (A) ◽  
pp. 1245-1251
Author(s):  
Sastia Winda Astuti ◽  
Isabella Kurnia Liem ◽  
Yetty Ramli
Keyword(s):  
Ischemic Stroke ◽  
Cord Blood ◽  
Rat Brain ◽  
Cortical Neurons ◽  
Mononuclear Cells ◽  
Neurological Deficits ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Cortical Neurogenesis ◽  
The Brain

BACKGROUND: Stroke is the second most cause of death in the world. There are several treatments but they often end up with disabilities. Recently, cell therapy has become a new hope as an alternative treatment as it could improve the patients neurological deficits and daily living activities. Cord blood mononuclear cells (CB-MNCs) are one of the cell therapies for post-ischemic neurogenesis by intravenous or intra-arterial administration; however, it is not clear which one is better. AIM: This study aims to compare the effects of intra-arterial and intravenous administration of human CB-MNC on cortical neurogenesis of rat brain after ischemic stroke. METHODS: Twenty-four rats were divided into four groups, that is, control, middle cerebral artery obstruction (MCAO) without treatment, MCAO with intra-arterial CB-MNC injection (MCAO-IA), and MCAO with intravenous CB-MNC injection (MCAO-IV). Two weeks after injection, all rats were sacrificed, the brain was harvested, histologically process and stained with hematoxylin eosin (HE) to determine cellular and tissue morphology changes, and immunohistochemical staining, anti-NeuN antibody to determine the number of cortical neurons. The HE showed that MCAO rat brain had gliosis and shrunken cells. RESULTS: The results showed that MCAO-IA and MCAO-IV had fewer areas of gliosis and shrunken cells when compared to the MCAO group. The number of neurons also showed an increase. However, there was no difference between the MCAO-IA and MCAO-IV groups. It was concluded both of them could improve neurogenesis. CONCLUSION: CB-MNC administration can be an alternative for stroke ischemic therapy because it is proven to increase neurogenesis and reduce gliosis areas. However, there was no difference in neurogenesis in the brain tissue of mice injected with CB-MNC intravenously or intra-arterially.

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