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Article ; Online: Translational Utility of the Nonhuman Primate Model.

Tarantal, Alice F / Hartigan-O'Connor, Dennis J / Noctor, Stephen C

Biological psychiatry. Cognitive neuroscience and neuroimaging

2022 Volume 7, Issue 5, Page(s) 491–497

Abstract: Nonhuman primates are essential for the study of human disease and to explore the safety of new diagnostics and therapies proposed for human use. They share similar genetic, physiologic, immunologic, reproductive, and developmental features with humans ... ...

Abstract	Nonhuman primates are essential for the study of human disease and to explore the safety of new diagnostics and therapies proposed for human use. They share similar genetic, physiologic, immunologic, reproductive, and developmental features with humans and thus have proven crucial for the study of embryonic/fetal development, organ system ontogeny, and the role of the maternal-placental-fetal interface in health and disease. The fetus may be exposed to a variety of inflammatory stimuli including infectious microbes as well as maternal inflammation, which can result from infections, obesity, or environmental exposures. Growing evidence supports that inflammation is a mediator of fetal programming and that the maternal immune system is tightly integrated with fetal-placental immune responses that may set a postnatal path for future health or disease. This review addresses some of the unique features of the nonhuman primate model system, specifically the rhesus monkey (Macaca mulatta), and importance of the species for studies focused on organ system ontogeny and the impact of viral teratogens in relation to development and congenital disorders.
MeSH term(s)	Animals ; Female ; Humans ; Inflammation ; Macaca mulatta ; Placenta ; Pregnancy
Language	English
Publishing date	2022-03-10
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2022.03.001
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Article ; Online: Nonhuman Primates in Translational Research.

Tarantal, Alice F / Noctor, Stephen C / Hartigan-O'Connor, Dennis J

Annual review of animal biosciences

2022 Volume 10, Page(s) 441–468

Abstract: Nonhuman primates are critically important animal models in which to study complex human diseases, understand biological functions, and address the safety of new diagnostics and therapies proposed for human use. They have genetic, physiologic, ... ...

Abstract	Nonhuman primates are critically important animal models in which to study complex human diseases, understand biological functions, and address the safety of new diagnostics and therapies proposed for human use. They have genetic, physiologic, immunologic, and developmental similarities when compared to humans and therefore provide important preclinical models of human health and disease. This review highlights select research areas that demonstrate the importance of nonhuman primates in translational research. These include pregnancy and developmental disorders, infectious diseases, gene therapy, somatic cell genome editing, and applications of in vivo imaging. The power of the immune system and our increasing understanding of the role it plays in acute and chronic illnesses are being leveraged to produce new treatments for a range of medical conditions. Given the importance of the human immune system in health and disease, detailed study of the immune system of nonhuman primates is essential to advance preclinical translational research. The need for nonhuman primates continues to remain a high priority, which has been acutely evident during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic. Nonhuman primates will continue to address key questions and provide predictive models to identify the safety and efficiency of new diagnostics and therapies for human use across the lifespan.
MeSH term(s)	Animals ; COVID-19/veterinary ; Disease Models, Animal ; Humans ; Primates/genetics ; SARS-CoV-2 ; Translational Research, Biomedical
Language	English
Publishing date	2022-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2700164-7
ISSN	2165-8110 ; 2165-8102
ISSN (online)	2165-8110
ISSN	2165-8102
DOI	10.1146/annurev-animal-021419-083813
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Article ; Online: Cortical Evolution Conference, 2018.

Martínez-Cerdeño, Verónica / Noctor, Stephen C

The Journal of comparative neurology

2019 Volume 527, Issue 10, Page(s) 1543–1544

MeSH term(s)	Animals ; Biological Evolution ; Cerebral Cortex ; Humans
Language	English
Publishing date	2019-03-01
Publishing country	United States
Document type	Congress ; Editorial ; Introductory Journal Article
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.24663
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Article ; Online: Decreased number and increased activation state of astrocytes in gray and white matter of the prefrontal cortex in autism.

Vakilzadeh, Gelareh / Falcone, Carmen / Dufour, Brett / Hong, Tiffany / Noctor, Stephen C / Martínez-Cerdeño, Verónica

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 32, Issue 21, Page(s) 4902–4912

Abstract: The cerebral cortex presents with alterations in the number of specific cell types in autism spectrum disorder (ASD). Astrocytes have many functions in the brain including a role in higher cognitive functions and in inflammatory brain processes. ... ...

Abstract	The cerebral cortex presents with alterations in the number of specific cell types in autism spectrum disorder (ASD). Astrocytes have many functions in the brain including a role in higher cognitive functions and in inflammatory brain processes. Therefore, an alteration in number, function, and/or activation state of astrocytes, could be present in ASD. We quantified astrocyte number in the gray and white matter of the prefrontal cortex-BA9, BA46, and BA47-in 15 ASD and 15 age- and sex-matched control cases. We labeled astrocytes with antibodies against the protein GFAP and S100β, markers of astrocytes. We found a significant decrease in the number of astrocytes in the gray and white matter of all prefrontal areas of interest with both markers. We also found an increased state of activation of GFAP+ astrocytes in all areas. A reduced number of astrocytes in the cerebral cortex in ASD could lead to impaired synaptic function and disrupted connectivity. An increased astrocyte activation may indicate a chronic mild inflammatory state of the cerebral cortex in ASD. Overall, we found that astrocytes are disrupted in ASD.
MeSH term(s)	Humans ; White Matter/metabolism ; Astrocytes/metabolism ; Autism Spectrum Disorder/metabolism ; Autistic Disorder/metabolism ; Prefrontal Cortex/metabolism ; Inflammation/metabolism ; Gray Matter/metabolism
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhab523
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Article: Microglia enhances proliferation of neural progenitor cells in an

Chounchay, Supanee / Noctor, Stephen C / Chutabhakdikul, Nuanchan

EXCLI journal

2020 Volume 19, Page(s) 950–961

Abstract: Microglial cells are the primary immune cells in the central nervous system. In the mature brain, microglia perform functions that include eliminating pathogens and clearing dead/dying cells and cellular debris through phagocytosis. In the immature brain, ...

Abstract	Microglial cells are the primary immune cells in the central nervous system. In the mature brain, microglia perform functions that include eliminating pathogens and clearing dead/dying cells and cellular debris through phagocytosis. In the immature brain, microglia perform functions that include synapse development and the regulation of cell production through extensive contact with and phagocytosis of neural progenitor cells (NPCs). However, the functional role of microglia in the proliferation and differentiation of NPCs under hypoxic-ischemic (HI) injury is not clear. Here, we tested the hypothesis that microglia enhance NPCs proliferation following HI insult. Primary NPCs cultures were divided into four treatment groups: 1) normoxic NPCs (NN); 2) normoxic NPCs cocultured with microglia (NN+M); 3) hypoxic NPCs (HN); and 4) hypoxic NPCs cocultured with microglia (HN+M). Hypoxic-ischemic injury was induced by pretreatment of the cell cultures with 100 µM deferoxamine mesylate (DFO). NPCs treated with 100 µM DFO (HN groups) for 24 hours had significantly increased expression of hypoxia-inducible factor 1 alpha (HIF-1α), a marker of hypoxic cells. Cell number, protein expression, mitosis, and cell cycle phase were examined, and the data were compared between the four groups. We found that the number of cells expressing the NPCs marker Sox2 increased significantly in the HN+M group and that the number of PH3-positive cells increased in the HN+M group; flow cytometry analysis showed a significant increase in the percentage of cells in the G2/M phase in the HN+M group. In summary, these results support the concept that microglia enhance the survival of NPCs under HI injury by increasing NPCs proliferation, survival, and differentiation. These results further suggest that microglia may induce neuroprotective effects after hypoxic injury that can be explored to develop novel therapeutic strategies for the treatment of HI injury in the immature brain.
Language	English
Publishing date	2020-07-03
Publishing country	Germany
Document type	Journal Article
ISSN	1611-2156
ISSN	1611-2156
DOI	10.17179/excli2020-2249
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Article ; Online: Cortical evolution 2018: Advantages of animal model species.

Martínez-Cerdeño, Verónica / Noctor, Stephen C

The Journal of comparative neurology

2018 Volume 527, Issue 10, Page(s) 1766–1768

MeSH term(s)	Animals ; Biological Evolution ; Cerebral Cortex ; Models, Animal
Language	English
Publishing date	2018-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.24536
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Article ; Online: Time-lapse imaging of fluorescently labeled live cells in the embryonic mammalian forebrain.

Noctor, Stephen C

Cold Spring Harbor protocols

2011 Volume 2011, Issue 11, Page(s) 1350–1361

Abstract: Time-lapse imaging of fluorescently labeled cells in organotypic slice culture provides a unique window through which to view development of the embryonic forebrain. The live imaging approach allows investigators to directly observe and record neurogenic ...

Abstract	Time-lapse imaging of fluorescently labeled cells in organotypic slice culture provides a unique window through which to view development of the embryonic forebrain. The live imaging approach allows investigators to directly observe and record neurogenic and gliogenic divisions in the developing forebrain, to record the proliferative behavior of embryonic precursor cells, and to track newborn cells as they migrate from the proliferative zones to their final destination. This approach allows for identification and characterization of embryonic precursor cells, permits the physiological and immunohistochemical characterization of the fluorescent cells under study, and presents an opportunity to test hypotheses about mechanisms that guide developmental processes in the forebrain. This article describes a protocol for time-lapse imaging of fluorescently labeled cells in the embryonic forebrain of organotypic slice cultures. The procedure does not require prohibitively expensive on-stage incubation systems, and can yield reliable data from embryonic slices for up to 1 wk. Tracking the movement of labeled cells in slice culture is relatively straightforward in those cases in which there are few labeled cells. Although this approach is time intensive, it provides beautifully detailed images that reveal morphological and functional data from labeled cells over time, and can yield a significant amount of data from each cell.
MeSH term(s)	Animals ; Microscopy, Fluorescence/methods ; Prosencephalon/cytology ; Prosencephalon/embryology ; Rats ; Staining and Labeling/methods ; Time-Lapse Imaging/methods
Language	English
Publishing date	2011-11-01
Publishing country	United States
Document type	Journal Article
ISSN	1559-6095
ISSN (online)	1559-6095
DOI	10.1101/pdb.prot066605
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Article: Neural Progenitor Cell Terminology.

Martínez-Cerdeño, Verónica / Noctor, Stephen C

Frontiers in neuroanatomy

2018 Volume 12, Page(s) 104

Abstract: Since descriptions of neural precursor cells (NPCs) were published in the late 19th century, neuroanatomists have used a variety of terms to describe these cells, each term reflecting contemporary understanding of cellular characteristics and function. ... ...

Abstract	Since descriptions of neural precursor cells (NPCs) were published in the late 19th century, neuroanatomists have used a variety of terms to describe these cells, each term reflecting contemporary understanding of cellular characteristics and function. As the field gained knowledge through a combination of technical advance and individual insight, the terminology describing NPCs changed to incorporate new information. While there is a trend toward consensus and streamlining of terminology over time, to this day scientists use different terms for NPCs that reflect their field and perspective, i.e., terms arising from molecular, cellular, or anatomical sciences. Here we review past and current terminology used to refer to NPCs, including embryonic and adult precursor cells of the cerebral cortex and hippocampus.
Language	English
Publishing date	2018-12-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2018.00104
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Article ; Online: The fundamental building blocks of cortical development are established in human exencephaly.

Falcone, Carmen / Vakilzadeh, Gelareh / Noctor, Stephen C / Martínez-Cerdeño, Verónica

Pediatric research

2019 Volume 87, Issue 5, Page(s) 868–871

Abstract: Background: The presence and status of progenitor/stem cells in excencephalic brain have not been previously examined.: Methods: Brain sections of excencephalic 17-week fetus were stained for specific stem and mature cell markers.: Results: The ... ...

Abstract	Background: The presence and status of progenitor/stem cells in excencephalic brain have not been previously examined. Methods: Brain sections of excencephalic 17-week fetus were stained for specific stem and mature cell markers. Results: The ventricles were open, the developing cerebral cortex was thin in the radial dimension, and the ventricular surface was undulated. There was a decreased ratio of subventricular/ventricular zone radial glia precursor cells (RGCs; PAX6 Conclusions: This indicates that the underlying condition did not initially preclude radial glial cells from undergoing asymmetric divisions that produce IPCs but halted the developmental progression. RGC and IPC presence in the developing cerebral cortex demonstrates that the fundamental building blocks of cortical formation had been established and that a normal sequence of developmental steps had been initiated in this case of exencephaly. These data expand our understanding of exencephaly etiology and highlight the status of cortical progenitor cells that may be linked to the disorder.
MeSH term(s)	Astrocytes/cytology ; Cell Differentiation ; Cerebral Cortex/embryology ; Female ; Humans ; Neural Stem Cells/cytology ; Neural Tube Defects/embryology ; Neural Tube Defects/pathology ; Neurogenesis ; Neuroglia/pathology ; Neurons/metabolism ; Oligodendroglia/cytology ; Phenotype ; Pregnancy ; Pregnancy Trimester, Second ; Stem Cells/cytology
Language	English
Publishing date	2019-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-019-0687-y
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Article ; Online: Development of the Neuro-Immune-Vascular Plexus in the Ventricular Zone of the Prenatal Rat Neocortex.

Penna, Elisa / Mangum, Jon M / Shepherd, Hunter / Martínez-Cerdeño, Veronica / Noctor, Stephen C

Cerebral cortex (New York, N.Y. : 1991)

2020 Volume 31, Issue 4, Page(s) 2139–2155

Abstract: Microglial cells make extensive contacts with neural precursor cells (NPCs) and affiliate with vasculature in the developing cerebral cortex. But how vasculature contributes to cortical histogenesis is not yet fully understood. To better understand ... ...

Abstract	Microglial cells make extensive contacts with neural precursor cells (NPCs) and affiliate with vasculature in the developing cerebral cortex. But how vasculature contributes to cortical histogenesis is not yet fully understood. To better understand functional roles of developing vasculature in the embryonic rat cerebral cortex, we investigated the temporal and spatial relationships between vessels, microglia, and NPCs in the ventricular zone. Our results show that endothelial cells in developing cortical vessels extend numerous fine processes that directly contact mitotic NPCs and microglia; that these processes protrude from vessel walls and are distinct from tip cell processes; and that microglia, NPCs, and vessels are highly interconnected near the ventricle. These findings demonstrate the complex environment in which NPCs are embedded in cortical proliferative zones and suggest that developing vasculature represents a source of signaling with the potential to broadly influence cortical development. In summary, cortical histogenesis arises from the interplay among NPCs, microglia, and developing vasculature. Thus, factors that impinge on any single component have the potential to change the trajectory of cortical development and increase susceptibility for altered neurodevelopmental outcomes.
MeSH term(s)	Animals ; Cerebral Ventricles/blood supply ; Cerebral Ventricles/cytology ; Cerebral Ventricles/embryology ; Embryonic Development/physiology ; Female ; Microglia/physiology ; Neocortex/blood supply ; Neocortex/cytology ; Neocortex/embryology ; Neural Stem Cells/physiology ; Neurogenesis/physiology ; Neuroimmunomodulation/physiology ; Pregnancy ; Rats
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhaa351
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