scholarly journals What happens to your brain on the way to Mars

2015 ◽  
Vol 1 (4) ◽  
pp. e1400256 ◽  
Author(s):  
Vipan K. Parihar ◽  
Barrett Allen ◽  
Katherine K. Tran ◽  
Trisha G. Macaraeg ◽  
Esther M. Chu ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Charged Particles ◽  
Radiation Sensitivity ◽  
Galactic Cosmic Rays ◽  
Spine Density ◽  
Neuronal Structure ◽  
Prefrontal Cortical ◽  
Radiation Induced ◽  
The Central Nervous System ◽  
The Brain

As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

scholarly journals Neuroinvasion of SARS-CoV-2 in human and mouse brain

2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Immune Cell ◽  
Multiple Organ ◽  
Type I ◽  
Organ Systems ◽  
The Central Nervous System ◽  
Interferon Responses ◽  
The Brain ◽  
Immune Cell Infiltrates

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

scholarly journals The accumulation of N6-methyl-2’-deoxyadenosine in DNA drives activity-induced gene expression and is required for the extinction of conditioned fear

2016 ◽  
Author(s):  
Xiang Li ◽  
Qiongyi Zhao ◽  
Wei Wei ◽  
Quan Lin ◽  
Christophe Magnan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cortical Neurons ◽  
Conditioned Fear ◽  
Fear Extinction ◽  
Adult Brain ◽  
Extinction Learning ◽  
Prefrontal Cortical ◽  
Genome Wide ◽  
Extinction Memory ◽  
The Brain

Here we report that the recently discovered mammalian DNA modification N6-methyl-2’-deoxyadenosine (m6dA) is dynamically regulated in primary cortical neurons, and accumulates along promoters and coding sequences within the genome of activated prefrontal cortical neurons of adult C57/BI6 mice in response to fear extinction learning. The deposition of m6dA is generally associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with fear extinction learning-induced gene expression. Of particular relevance for fear extinction memory, the accumulation of m6dA is associated with an active chromatin state and the recruitment of transcriptional machinery to the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV mRNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as a novel neuroepigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

scholarly journals Fingolimod Modulates Dendritic Architecture in a BDNF-Dependent Manner

2020 ◽  
Vol 21 (9) ◽  
pp. 3079 ◽  
Author(s):  
Abhisarika Patnaik ◽  
Eleonora Spiombi ◽  
Angelisa Frasca ◽  
Nicoletta Landsberger ◽  
Marta Zagrebelsky ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Rett Syndrome ◽  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Neurological Diseases ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Spine Density ◽  
Neuronal Structure ◽  
Cellular Mechanisms

The brain-derived neurotrophic factor (BDNF) plays crucial roles in both the developing and mature brain. Moreover, alterations in BDNF levels are correlated with the cognitive impairment observed in several neurological diseases. Among the different therapeutic strategies developed to improve endogenous BDNF levels is the administration of the BDNF-inducing drug Fingolimod, an agonist of the sphingosine-1-phosphate receptor. Fingolimod treatment was shown to rescue diverse symptoms associated with several neurological conditions (i.e., Alzheimer disease, Rett syndrome). However, the cellular mechanisms through which Fingolimod mediates its BDNF-dependent therapeutic effects remain unclear. We show that Fingolimod regulates the dendritic architecture, dendritic spine density and morphology of healthy mature primary hippocampal neurons. Moreover, the application of Fingolimod upregulates the expression of activity-related proteins c-Fos and pERK1/2 in these cells. Importantly, we show that BDNF release is required for these actions of Fingolimod. As alterations in neuronal structure underlie cognitive impairment, we tested whether Fingolimod application might prevent the abnormalities in neuronal structure typical of two neurodevelopmental disorders, namely Rett syndrome and Cdk5 deficiency disorder. We found a significant rescue in the neurite architecture of developing cortical neurons from Mecp2 and Cdkl5 mutant mice. Our study provides insights into understanding the BDNF-dependent therapeutic actions of Fingolimod.

scholarly journals Astrocyte-derived thrombospondin induces cortical synaptogenesis in a sex-specific manner

2021 ◽  
Author(s):  
Anna Mazur ◽  
Ean H. Bills ◽  
Brandon J. Henderson ◽  
W. Christopher Risher
Keyword(s):  
Cortical Neurons ◽  
Neuronal Response ◽  
Male Rats ◽  
Estrogen Signaling ◽  
Synaptic Connectivity ◽  
The Central Nervous System ◽  
17Β Estradiol ◽  
Males And Females ◽  
Cortical Synapses ◽  
The Brain

AbstractThe regulation of synaptic connectivity in the brain is vital to proper functioning and development of the central nervous system (CNS). Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared to female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to TSP2, which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17β-estradiol production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that TSP-induced synaptogenesis is critical for the development of male but not female cortical synapses, contributing to sex differences in astrocyte-mediated synaptic connectivity.

scholarly journals Neuroinvasion of SARS-CoV-2 in human and mouse brain

2020 ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Immune Cell ◽  
Multiple Organ ◽  
Cns Infection ◽  
Type I ◽  
Organ Systems ◽  
Pathologic Features ◽  
The Central Nervous System ◽  
The Brain

SummaryAlthough COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Sign in / Sign up

Export Citation Format

Share Document