scholarly journals nor-1 Regulates Hippocampal Axon Guidance, Pyramidal Cell Survival, and Seizure Susceptibility

2004 ◽  
Vol 24 (20) ◽  
pp. 9070-9078 ◽  
Author(s):  
Tiia Pönniö ◽  
Orla M. Conneely
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Axonal Guidance ◽  
Seizure Susceptibility ◽  
Mammalian Development

ABSTRACT The nuclear receptor transcription factor, nor-1, is expressed during mammalian development predominantly in the nervous system and is induced in a cell-specific manner in nonneuronal cells in response to a variety of extracellular stimuli. To elucidate the essential developmental functions of this transcription factor, we have analyzed the consequences of its elimination on central nervous system development in mice. Here we show that null mutant mice lacking nor-1 respond with increased limbic seizure activity to the excitotoxic glutamate receptor agonist kainic acid. We demonstrate that these abnormalities are associated with defective postnatal hippocampal development exemplified by abnormal axonal guidance of dentate gyrus granule and mossy cells, disorganization of the pyramidal cell layer, and early postnatal death of pyramidal neurons in the CA1 field of the hippocampus. Our data indicate that nor-1 plays a critical role in neuronal survival and axonal guidance in the developing murine hippocampus and that hippocampal dysgenesis in nor-1−/− mice may be an underlying cause of seizure susceptibility.

scholarly journals Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Noriko Shinjyo ◽  
Wataru Kagaya ◽  
Marcela Pekna
Keyword(s):  
Nervous System ◽  
Complement System ◽  
Complement Activation ◽  
Neural Plasticity ◽  
Measles Virus ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Infectious Agents ◽  
The Complement System

As part of the innate immune system, complement plays a critical role in the elimination of pathogens and mobilization of cellular immune responses. In the central nervous system (CNS), many complement proteins are locally produced and regulate nervous system development and physiological processes such as neural plasticity. However, aberrant complement activation has been implicated in neurodegeneration, including Alzheimer’s disease. There is a growing list of pathogens that have been shown to interact with the complement system in the brain but the short- and long-term consequences of infection-induced complement activation for neuronal functioning are largely elusive. Available evidence suggests that the infection-induced complement activation could be protective or harmful, depending on the context. Here we summarize how various infectious agents, including bacteria (e.g., Streptococcus spp.), viruses (e.g., HIV and measles virus), fungi (e.g., Candida spp.), parasites (e.g., Toxoplasma gondii and Plasmodium spp.), and prion proteins activate and manipulate the complement system in the CNS. We also discuss the potential mechanisms by which the interaction between the infectious agents and the complement system can play a role in neurodegeneration and dementia.

scholarly journals Smad1 and Smad8 Function Similarly in Mammalian Central Nervous System Development

2005 ◽  
Vol 25 (11) ◽  
pp. 4683-4692 ◽  
Author(s):  
Mark Hester ◽  
John C. Thompson ◽  
Joseph Mills ◽  
Ye Liu ◽  
Heithem M. El-Hodiri ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bone Morphogenetic Proteins ◽  
System Development ◽  
Nervous System Development ◽  
Mammalian Development ◽  
Hypomorphic Allele ◽  
Mammalian Central Nervous System ◽  
Neomycin Cassette ◽  
Intracellular Mediators

ABSTRACT Smads 1, 5, and 8 are the intracellular mediators for the bone morphogenetic proteins (BMPs), which play crucial roles during mammalian development. Previous research has shown that Smad1 is important in the formation of the allantois, while Smad5 has been shown to be critical in the process of angiogenesis. To further analyze the BMP-responsive Smads, we disrupted the murine Smad8 gene utilizing the Cre/loxP system. A Smad8 hypomorphic allele (Smad8 Δexon3 ) was constructed that contains an in-frame deletion of exon 3, removing one-third of the MH2 domain and a small portion of the linker region. Xenopus injection assays indicated that this Smad8 deletion allele is still functional but has reduced ventralizing capability compared to the wild type. Although Smad8 Δexon3/Δexon3 embryos are phenotypically normal, homozygotes of another hypomorphic allele of Smad8 (Smad8 3loxP ) containing a neomycin cassette within intron 3, phenocopy an embryonic brain defect observed in roughly 22% of Smad1 +/ − embryos analyzed at embryonic day 11.5. These observations suggest that BMP-responsive Smads have critical functions in the development of the mammalian central nervous system.

scholarly journals Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development

2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Alison T. DePew ◽  
Timothy J. Mosca
Keyword(s):  
Nervous System ◽  
Cell Surface ◽  
Current Knowledge ◽  
System Development ◽  
Critical Role ◽  
Surface Protein ◽  
Nervous System Development ◽  
Cell Surface Receptor ◽  
Synaptic Development ◽  
Disease Etiology

As the nervous system develops, connections between neurons must form to enable efficient communication. This complex process of synaptic development requires the coordination of a series of intricate mechanisms between partner neurons to ensure pre- and postsynaptic differentiation. Many of these mechanisms employ transsynaptic signaling via essential secreted factors and cell surface receptors to promote each step of synaptic development. One such cell surface receptor, LRP4, has emerged as a synaptic organizer, playing a critical role in conveying extracellular signals to initiate diverse intracellular events during development. To date, LRP4 is largely known for its role in development of the mammalian neuromuscular junction, where it functions as a receptor for the synaptogenic signal Agrin to regulate synapse development. Recently however, LRP4 has emerged as a synapse organizer in the brain, where new functions for the protein continue to arise, adding further complexity to its already versatile roles. Additional findings indicate that LRP4 plays a role in disorders of the nervous system, including myasthenia gravis, amyotrophic lateral sclerosis, and Alzheimer’s disease, demonstrating the need for further study to understand disease etiology. This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections.

scholarly journals The role of astrocyte‐mediated plasticity in neural circuit development and function

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Nelson A. Perez-Catalan ◽  
Chris Q. Doe ◽  
Sarah D. Ackerman
Keyword(s):  
Nervous System ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Functional Changes ◽  
Sensory Evoked ◽  
And Function

AbstractNeuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.

scholarly journals Deficiency of Pro-apoptotic Hrk Attenuates Programmed Cell Death in the Developing Murine Nervous System but Does Not Affect Bcl-x Deficiency-Induced Neuron Apoptosis

2011 ◽  
Vol 59 (11) ◽  
pp. 976-983 ◽  
Author(s):  
Arindam P. Ghosh ◽  
Jennifer D. Cape ◽  
Barbara J. Klocke ◽  
Kevin A. Roth
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
System Development ◽  
Critical Role ◽  
Family Members ◽  
Nervous System Development ◽  
Neuronal Populations ◽  
Embryonic Nervous System ◽  
Induced Neuron

The BCL-2 family includes both pro- and anti-apoptotic proteins, which regulate programmed cell death during development and in response to various apoptotic stimuli. The BH3-only subgroup of pro-apoptotic BCL-2 family members is critical for the induction of apoptotic signaling, by binding to and neutralizing anti-apoptotic BCL-2 family members. During embryonic development, the anti-apoptotic protein BCL-XL plays a critical role in the survival of neuronal populations by regulating the multi-BH domain protein BAX. In this study, the authors investigated the role of Harakiri (HRK), a relatively recently characterized BH3-only molecule in disrupting the BAX-BCL-XL interaction during nervous system development. Results indicate that HRK deficiency significantly reduces programmed cell death in the nervous system. However, HRK deficiency does not significantly attenuate the widespread apoptosis seen in the Bcl-x−/− embryonic nervous system, indicating that other BH3-only molecules, alone or in combination, may regulate BAX activation in immature neurons.

scholarly journals THE DEVELOPMENT OF NEUROINFLAMMATORY PROCESSES IN RATS IN EARLY POSTNATAL ONTOGENESIS AFTER PRENATAL HYPERHOMOCYSTEINEMIA

2019 ◽  
Vol 19 (1S) ◽  
pp. 234-235
Author(s):  
A D Shcherbitskaia ◽  
D S Vasilev ◽  
N L Tumanova ◽  
Ju P Milyutina ◽  
I V Zalozniaia ◽  
...  
Keyword(s):  
Nervous System ◽  
Pyramidal Neurons ◽  
System Development ◽  
Nervous System Development ◽  
Early Postnatal Ontogenesis ◽  
Prenatal Hyperhomocysteinemia ◽  
Gestational Exposure ◽  
And Migration ◽  
Long Term Impact

Prenatal exposure to high levels of homocysteine has long-term impact on growth retardation of nervous system development and is related to central nervous system diseases in children. However, it is not well-characterized whether gestational exposure to hyperhomocysteinemia (HHC) affects the development of nervous system in offspring. It was observed disturbed neuroblast generation and migration, neuronal death in cortex, revealed as reduction of pyramidal neurons number, and activation of glia in the month after birth in offspring subjected to HHC. These disorders may be associated with changes in the content of pro-inflammatory cytokines in the cortex tissue of HHC pups.

scholarly journals The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009475
Author(s):  
Leo T. H. Tang ◽  
Meera Trivedi ◽  
Jenna Freund ◽  
Christopher J. Salazar ◽  
Maisha Rahman ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuronal Development ◽  
System Development ◽  
Nervous System Development ◽  
Axonal Guidance ◽  
Neural Patterning ◽  
Dendritic Trees ◽  
Important Regulator ◽  
P Type ◽  
Dendrite Morphogenesis

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.

Sign in / Sign up

Export Citation Format

Share Document