PSA Depletion Induces the Differentiation of Immature Neurons in the Piriform Cortex of Adult Mice

Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.

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Anatomical development of the cerebellothalamic tract in embryonic mice

10.1101/731968 ◽

2019 ◽

Author(s):

Daniël B. Dumas ◽

Simona V. Gornati ◽

Youri Adolfs ◽

Tomomi Shimogori ◽

R. Jeroen Pasterkamp ◽

...

Keyword(s):

Cerebral Cortex ◽

Neurodevelopmental Disorders ◽

Developmental Disorders ◽

Light Sheet ◽

Autism Spectrum ◽

Adult Brain ◽

Mammalian Brain ◽

Wide Field ◽

Thalamic Nuclei ◽

Cortical Regions

AbstractCerebellar projections to the thalamus are a pivotal connection in cerebello-cerebral interactions. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic projection has also been implemented in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied in many species, a detailed description of the ontogeny of the mammalian cerebello-thalamic tract (CbT) is currently missing. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation (IUE) of wild type mice. Wide-field, confocal and 3D light-sheet imaging of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex become increasingly innervated. Several CbT fiber varicosities colocalize with vGluT2, indicating that already from E18.5 the CbT synapse in various thalamic nuclei. Our results contribute to the construction of a frame of reference on the anatomical development of the CbT, which will help to guide future experiments investigating neurodevelopmental disorders.Significance statementUsing various microscopic approaches, we investigated the anatomical development of the fiber tract between the cerebellum and thalamus, one of the major mammalian brain connections. Our results show that in mice cerebellar axons wait outside of the thalamus from embryonic day (E)15.5 until E17.5 before invading the thalamic complex. Cerebellar axons establish vGluT2-positive synapses at E18.5 throughout various thalamic nuclei, each of which subsequently develops its connections with dedicated cerebral cortical regions. Our data thereby advocate the cerebellar influence on the maturation of the thalamus and connected cerebral cortex. This knowledge can help to guide future experiments into neurodevelopmental disorders affecting cerebello-thalamo-cortical networks.

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Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

10.1101/490680 ◽

2018 ◽

Author(s):

Edwin Wong ◽

Stephen D Glasgow ◽

Lianne J Trigiani ◽

Daryan Chitsaz ◽

Vladmir Rymar ◽

...

Keyword(s):

Spatial Memory ◽

Learning And Memory ◽

Critical Role ◽

Long Term Potentiation ◽

Memory Formation ◽

Adult Brain ◽

Mammalian Brain ◽

Conditional Deletion ◽

The Impact ◽

Adult Mammalian Brain

Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the post-natal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behaviour. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

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Newly Generated and Non-Newly Generated “Immature” Neurons in the Mammalian Brain: A Possible Reservoir of Young Cells to Prevent Brain Aging and Disease?

Journal of Clinical Medicine ◽

10.3390/jcm8050685 ◽

2019 ◽

Vol 8 (5) ◽

pp. 685 ◽

Cited By ~ 10

Author(s):

Chiara La Rosa ◽

Marco Ghibaudi ◽

Luca Bonfanti

Keyword(s):

Neurological Disorders ◽

Brain Aging ◽

Brain Plasticity ◽

Brain Regions ◽

Mammalian Brain ◽

Brain Health ◽

Immature Neurons ◽

Potential Reservoir ◽

The Impact ◽

Stem Cell Niches

Brain plasticity is important for translational purposes since most neurological disorders and brain aging problems remain substantially incurable. In the mammalian nervous system, neurons are mostly not renewed throughout life and cannot be replaced. In humans, the increasing life expectancy explains the increase in brain health problems, also producing heavy social and economic burden. An exception to the “static” brain is represented by stem cell niches leading to the production of new neurons. Such adult neurogenesis is dramatically reduced from fish to mammals, and in large-brained mammals with respect to rodents. Some examples of neurogenesis occurring outside the neurogenic niches have been reported, yet these new neurons actually do not integrate in the mature nervous tissue. Non-newly generated, “immature” neurons (nng-INs) are also present: Prenatally generated cells continuing to express molecules of immaturity (mostly shared with the newly born neurons). Of interest, nng-INs seem to show an inverse phylogenetic trend across mammals, being abundant in higher-order brain regions not served by neurogenesis and providing structural plasticity in rather stable areas. Both newly generated and nng-INs represent a potential reservoir of young cells (a “brain reserve”) that might be exploited for preventing the damage of aging and/or delay the onset/reduce the impact of neurological disorders.

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Effects and Potential Mechanisms of Alcohol Use Disorder on the Fate Determination of Newly Born Neurons in the Hippocampus

Alcohol and Alcoholism ◽

10.1093/alcalc/agaa083 ◽

2020 ◽

Vol 55 (6) ◽

pp. 598-602

Author(s):

Zahra Shabani ◽

Mohsen Jafarzadeh Gharehziaaddin

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Brain ◽

Adult Hippocampal Neurogenesis ◽

Mammalian Brain ◽

Extrinsic Factors ◽

Proliferation And Differentiation ◽

Underlying Mechanisms

Abstract In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.

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CCL11 Differentially Affects Post-Stroke Brain Injury and Neuroregeneration in Mice Depending on Age

Cells ◽

10.3390/cells9010066 ◽

2019 ◽

Vol 9 (1) ◽

pp. 66

Author(s):

Simone Lieschke ◽

Bozena Zechmeister ◽

Matteo Haupt ◽

Xuan Zheng ◽

Fengyan Jin ◽

...

Keyword(s):

Brain Injury ◽

Cell Injury ◽

Adult Brain ◽

Lymphocyte Migration ◽

Stroke Treatment ◽

Post Stroke ◽

Adult Mice ◽

Interesting Approach ◽

The Impact ◽

First Time

CCL11 has recently been shown to differentially affect cell survival under various pathological conditions including stroke. Indeed, CCL11 promotes neuroregeneration in neonatal stroke mice. The impact of CCL11 on the adult ischemic brain, however, remains elusive. We therefore studied the effect of ectopic CCL11 on both adolescent (six-week) and adult (six-month) C57BL6 mice exposed to stroke. Intraperitoneal application of CCL11 significantly aggravated acute brain injury in adult mice but not in adolescent mice. Likewise, post-stroke neurological recovery after four weeks was significantly impaired in adult mice whilst CCL11 was present. On the contrary, CCL11 stimulated gliogenesis and neurogenesis in adolescent mice. Flow cytometry analysis of blood and brain samples revealed a modification of inflammation by CCL11 at subacute stages of the disease. In adolescent mice, CCL11 enhances microglial cell, B and T lymphocyte migration towards the brain, whereas only the number of B lymphocytes is increased in the adult brain. Finally, the CCL11 inhibitor SB297006 significantly reversed the aforementioned effects. Our study, for the first time, demonstrates CCL11 to be a key player in mediating secondary cell injury under stroke conditions. Interfering with this pathway, as shown for SB297006, might thus be an interesting approach for future stroke treatment paradigms.

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Adult Neurogenesis: From Precursors to Network and Physiology

Physiological Reviews ◽

10.1152/physrev.00055.2003 ◽

2005 ◽

Vol 85 (2) ◽

pp. 523-569 ◽

Cited By ~ 668

Author(s):

Djoher Nora Abrous ◽

Muriel Koehl ◽

Michel Le Moal

Keyword(s):

Adult Neurogenesis ◽

Brain Plasticity ◽

Current Knowledge ◽

Hippocampal Formation ◽

Functional Integration ◽

Brain Regions ◽

Biological Properties ◽

Adult Brain ◽

Mammalian Brain ◽

Extrinsic Factors

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.

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DAMPAK KEBIJAKAN FISKAL TERHADAP KINERJA SEKTOR PERTANIAN DI SULAWESI TENGGARA

Jurnal Sosio Agribisnis ◽

10.33772/jsa.v1i1.1826 ◽

2017 ◽

Vol 1 (1) ◽

Author(s):

La Ode Jabuddin ◽

Ayub M Padangaran ◽

Azhar Bafadal Bafadal

Keyword(s):

Fiscal Policy ◽

Interest Rates ◽

Agricultural Sector ◽

Simultaneous Equations ◽

Poor People ◽

Land Area ◽

Factors Affecting ◽

Historical Simulation ◽

The Impact ◽

Direct Expenditure

This study aims to: (1) Knowing the dynamics of fiscal policy and the performance of the agricultural sector, (2) Analyze the factors that influence fiscal policy and the performance of the agricultural sector, and (3) Analyzing the impact of fiscal policy on the performance of the agricultural sector. The data used in this study were pooled 2005-2013 data in the aggregate. Econometric model the impact of fiscal policy on the performance of the agricultural sector is built in the form of simultaneous equations, consisting of 7 equations with 25 total variables in the model, 7 endogenous variables, 12 exogenous variables, and 6 variables lag. The model is estimated by 2SLS method SYSLIN procedures and historical simulation with SIMNLIN procedure.The results showed that: (1) The development of fiscal policy in Southeast Sulawesi from year to year tends to increase, (2) The performance of the agricultural sector from the aspect of GDP has decreased, from the aspect of labor is still consistent, in terms of investment to grow positively, and assign roles which means to decrease the number of poor people, (3) factors affecting fiscal policy is local revenues, equalization funds, other revenues, as well as the lag fiscal policy, (4) the factors that affect the performance of the agricultural sector from the aspect GDP is labor, direct expenditure and GDP lag; from the aspect of labor is the total labor force, investment, land area, direct expenditure, as well as the lag of labor; from the aspect of investment is influenced by GDP per capita, land area, interest rates and investment lag; as well as from the aspect of poor people, are affected by population, investments, direct expenditure and poverty lag, (5). Fiscal policy impact on the agricultural sector GDP increase, a decrease in the number of poor, declining agricultural laborers, and a decrease in the amount of investment in the agricultural sector.Keywords: Fiscal policy, the performance of the agricultural sector, the simultaneous equations

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Structural Model of Service Quality Factors Affecting Loyalty Sustainability

International Journal of Sustainable Construction Engineering Technology ◽

10.30880/ijscet.2020.11.02.026 ◽

2020 ◽

Vol 11 (2) ◽

Author(s):

Eman Al-erqi ◽

◽

Mohd Lizam Mohd Diah ◽

Najmaddin Abo Mosali ◽

◽

...

Keyword(s):

International Students ◽

Service Quality ◽

Goodness Of Fit ◽

Structural Model ◽

Quality Factors ◽

Factors Affecting ◽

Measurement Models ◽

Confirmatory Factor ◽

The University ◽

The Impact

This study seeks to address the impact of service quality affecting international student's satisfaction towards loyalty tothe Universiti Tun Hussein Onn Malaysia(UTHM). The aim of thestudy is to develop relationship between service quality factor and loyalty to the university from the international students’ perspectives. The study adopted quantitative approach where data was collected through questionnaire survey and analysed statistically. A total of 246 responses were received and found to be valid. The model was developed and analysed using AMOS-SEM software. Confirmatory factor analysis (CFA) function of the software was to assessed the measurement models and found that all the models achieved goodness of fit. Then path analysis function was used to assessed structural model and found that service qualityfactors have a significant effect on the students’ satisfaction and thus affecting the loyaltyto the university. Hopefully the outcome form this study will benefit the university in providing services especially to the international students.

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