scholarly journals “Retrotransposition bursts” in the adult brain: Stress, running, and operant learning increase the number of L1 retrotransposon DNA copies in the mouse brain

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S314
Author(s):  
Konstantin Anokhin ◽  
Olga Ivashkina
Keyword(s):  
Mouse Brain ◽  
Adult Brain ◽  
Operant Learning ◽  
L1 Retrotransposon

Myf5 is a novel early axonal marker in the mouse brain and is subjected to post-transcriptional regulation in neurons

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 319-331 ◽  
Author(s):  
P. Daubas ◽  
S. Tajbakhsh ◽  
J. Hadchouel ◽  
M. Primig ◽  
M. Buckingham
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Mrna Translation ◽  
Adult Brain ◽  
Protein Accumulation ◽  
Embryonic Mouse ◽  
Signalling Molecules ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Brain

Myf5 is a key basic Helix-Loop-Helix transcription factor capable of converting many non-muscle cells into muscle. Together with MyoD it is essential for initiating the skeletal muscle programme in the embryo. We previously identified unexpected restricted domains of Myf5 transcription in the embryonic mouse brain, first revealed by Myf5-nlacZ(+/)(−) embryos (Tajbakhsh, S. and Buckingham, M. (1995) Development 121, 4077–4083). We have now further characterized these Myf5 expressing neurons. Retrograde labeling with diI, and the use of a transgenic mouse line expressing lacZ under the control of Myf5 regulatory sequences, show that Myf5 transcription provides a novel axonal marker of the medial longitudinal fasciculus (mlf) and the mammillotegmental tract (mtt), the earliest longitudinal tracts to be established in the embryonic mouse brain. Tracts projecting caudally from the developing olfactory system are also labelled. nlacZ and lacZ expression persist in the adult brain, in a few ventral domains such as the mammillary bodies of the hypothalamus and the interpeduncular nucleus, potentially derived from the embryonic structures where the Myf5 gene is transcribed. To investigate the role of Myf5 in the brain, we monitored Myf5 protein accumulation by immunofluorescence and immunoblotting in neurons transcribing the gene. Although Myf5 was detected in muscle myotomal cells, it was absent in neurons. This would account for the lack of myogenic conversion in brain structures and the absence of a neural phenotype in homozygous null mutants. RT-PCR experiments show that the splicing of Myf5 primary transcripts occurs correctly in neurons, suggesting that the lack of Myf5 protein accumulation is due to regulation at the level of mRNA translation or protein stability. In the embryonic neuroepithelium, Myf5 is transcribed in differentiated neurons after the expression of neural basic Helix-Loop-Helix transcription factors. The signalling molecules Wnt1 and Sonic hedgehog, implicated in the activation of Myf5 in myogenic progenitor cells in the somite, are also produced in the viscinity of the Myf5 expression domain in the mesencephalon. We show that cells expressing Wnt1 can activate neuronal Myf5-nlacZ gene expression in dissected head explants isolated from E9.5 embryos. Furthermore, the gene encoding the basic Helix-Loop-Helix transcription factor mSim1 is expressed in adjacent cells in both the somite and the brain, suggesting that signalling molecules necessary for the activation of mSim1 as well as Myf5 are present at these different sites in the embryo. This phenomenon may be widespread and it remains to be seen how many other potentially potent regulatory genes, in addition to Myf5, when activated do not accumulate protein at inappropriate sites in the embryo.

scholarly journals Expression of Heparan Sulfate Endosulfatases in the Adult Mouse Brain: Co-expression of Sulf1 and Dopamine D1/D2 Receptors

2021 ◽  
Vol 15 ◽  
Author(s):  
Ken Miya ◽  
Kazuko Keino-Masu ◽  
Takuya Okada ◽  
Kenta Kobayashi ◽  
Masayuki Masu
Keyword(s):  
Heparan Sulfate ◽  
Mouse Brain ◽  
Adult Mouse ◽  
Extracellular Enzymes ◽  
Expression Patterns ◽  
D2 Receptor ◽  
Adult Brain ◽  
Nucleus Accumbens Shell ◽  
Adult Mouse Brain ◽  
Double Labeling

The heparan sulfate 6-O-endosulfatases, Sulfatase 1 (Sulf1), and Sulfatase 2 (Sulf2), are extracellular enzymes that regulate cellular signaling by removing 6-O-sulfate from the heparan sulfate chain. Although previous studies have revealed that Sulfs are essential for normal development, their functions in the adult brain remain largely unknown. To gain insight into their neural functions, we used in situ hybridization to systematically examine Sulf1/2 mRNA expression in the adult mouse brain. Sulf1 and Sulf2 mRNAs showed distinct expression patterns, which is in contrast to their overlapping expression in the embryonic brain. In addition, we found that Sulf1 was distinctly expressed in the nucleus accumbens shell, the posterior tail of the striatum, layer 6 of the cerebral cortex, and the paraventricular nucleus of the thalamus, all of which are target areas of dopaminergic projections. Using double-labeling techniques, we showed that Sulf1-expressing cells in the above regions coincided with cells expressing the dopamine D1 and/or D2 receptor. These findings implicate possible roles of Sulf1 in modulation of dopaminergic transmission and dopamine-mediated behaviors.

scholarly journals The CD38-independent ADP-ribosyl cyclase from mouse brain synaptosomes: a comparative study of neonate and adult brain

2006 ◽  
Vol 395 (2) ◽  
pp. 417-426 ◽  
Author(s):  
Claire Ceni ◽  
Nathalie Pochon ◽  
Michel Villaz ◽  
Hélène Muller-Steffner ◽  
Francis Schuber ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neuronal Excitability ◽  
Major Effect ◽  
Hplc Method ◽  
Adult Brain ◽  
Free Calcium ◽  
Neural Cells ◽  
Intracellular Enzyme ◽  
Synaptic Terminals ◽  
Adp Ribosyl Cyclase

cADPR (cADP-ribose), a metabolite of NAD+, is known to modulate intracellular calcium levels and to be involved in calcium-dependent processes, including synaptic transmission, plasticity and neuronal excitability. However, the enzyme that is responsible for producing cADPR in the cytoplasm of neural cells, and particularly at the synaptic terminals of neurons, remains unknown. In the present study, we show that endogenous concentrations of cADPR are much higher in embryonic and neonate mouse brain compared with the adult tissue. We also demonstrate, by comparing wild-type and Cd38−/− tissues, that brain cADPR content is independent of the presence of CD38 (the best characterized mammalian ADP-ribosyl cyclase) not only in adult but also in developing tissues. We show that Cd38−/− synaptosome preparations contain high ADP-ribosyl cyclase activities, which are more important in neonates than in adults, in line with the levels of endogenous cyclic nucleotide. By using an HPLC method and adapting the cycling assay developed initially to study endogenous cADPR, we accurately examined the properties of the synaptosomal ADP-ribosyl cyclase. This intracellular enzyme has an estimated Km for NAD+ of 21 μM, a broad optimal pH at 6.0–7.0, and the concentration of free calcium has no major effect on its cADPR production. It binds NGD+ (nicotinamide–guanine dinucleotide), which inhibits its NAD+-metabolizing activities (Ki=24 μM), despite its incapacity to cyclize this analogue. Interestingly, it is fully inhibited by low (micromolar) concentrations of zinc. We propose that this novel mammalian ADP-ribosyl cyclase regulates the production of cADPR and therefore calcium levels within brain synaptic terminals. In addition, this enzyme might be a potential target of neurotoxic Zn2+.

scholarly journals In vivo Chemical Reprogramming of Astrocytes into Functional Neurons

2018 ◽  
Author(s):  
Yantao Ma ◽  
Handan Xie ◽  
Xiaomin Du ◽  
Lipeng Wang ◽  
Xueqin Jin ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mouse Brain ◽  
Adult Brain ◽  
Specific Marker ◽  
Electrophysiological Properties ◽  
Chemically Induced ◽  
Chemical Reprogramming ◽  
Induced Neurons

AbstractMammals lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced reprogramming is a spatiotemporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for the in vivo reprogramming in organs with poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram resident astrocytes into functional neurons. The in situ chemically induced neurons (CiNs) resemble endogenous neurons in terms of neuron-specific marker expression and electrophysiological properties. Importantly, these CiNs can integrate into the mouse brain. Our study, for the first time, demonstrates in vivo chemical reprogramming in the adult brain, which could be a novel path for generating desired cells in situ for regenerative medicine.

scholarly journals Molecular Atlas of the Adult Mouse Brain

2019 ◽  
Author(s):  
Cantin Ortiz ◽  
Jose Fernandez Navarro ◽  
Aleksandra Jurek ◽  
Antje Märtin ◽  
Joakim Lundeberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Spatial Organization ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Adult Mouse Brain ◽  
Whole Brain ◽  
Systematic Classification ◽  
Molecular Code

AbstractBrain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette – that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains.

scholarly journals Scaling of gene transcriptional gradients with brain size across mouse development

2020 ◽  
Author(s):  
Lau Hoi Yan Gladys ◽  
Alex Fornito ◽  
Ben D. Fulcher
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Brain Size ◽  
Structural Connectivity ◽  
Adult Brain ◽  
Brain Atlas ◽  
Mouse Development ◽  
Time Points ◽  
Scaling Relationship ◽  
Exponential Distance

The structure of the adult brain is the result of complex physical mechanisms acting through development. These physical processes, acting in threedimensional space, mean that the brain’s spatial embedding plays a key role in its organization, including the gradient-like patterning of gene expression that encodes the molecular underpinning of functional specialization. However, we do not yet understand how the dramatic changes in brain shape and size that occur in early development influence the brain’s transcriptional architecture. Here we investigate the spatial embedding of transcriptional patterns of over 1800 genes across seven time points through mousebrain development using data from the Allen Developing Mouse Brain Atlas. We find that transcriptional similarity decreases exponentially with separation distance across all developmental time points, with a correlation length scale that follows a powerlaw scaling relationship with a linear dimension of brain size. This scaling suggests that the mouse brain achieves a characteristic balance between local molecular similarity (homogeneous gene expression within a specialized brain area) and longer-range diversity (between functionally specialized brain areas) throughout its development. Extrapolating this mouse developmental scaling relationship to the human cortex yields a prediction consistent with the value measured from microarray data. We introduce a simple model of brain growth as spatially autocorrelated gene-expression gradients that expand through development, which captures key features of the mouse developmental data. Complementing the well-known exponential distance rule for structural connectivity, our findings characterize an analogous exponential distance rule for transcriptional gradients that scales across mouse brain development, providing new understanding of spatial constraints on the brain’s molecular patterning.

scholarly journals Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Anthony N. van den Pol ◽  
Guochao Mao ◽  
Anasuya Chattopadhyay ◽  
John K. Rose ◽  
John N. Davis
Keyword(s):  
Mouse Brain ◽  
Vesicular Stomatitis Virus ◽  
Adult Mouse ◽  
Semliki Forest Virus ◽  
Adult Brain ◽  
Adult Mouse Brain ◽  
Glycoprotein Gene ◽  
Vesicular Stomatitis ◽  
The Brain ◽  
Chimeric Viruses

ABSTRACT Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene. We also test a virus-like vesicle (VLV) in which the VSV glycoprotein gene is expressed from a replicon encoding the nonstructural proteins of Semliki Forest virus. VSVΔG-CHIKV, VSVΔG-H5N1, and VLV were all safe in the adult mouse brain, as were VSVΔG viruses expressing either the Nipah F or G glycoprotein. In contrast, a complementing pair of VSVΔG viruses expressing Nipah G and F glycoproteins were lethal within the brain within a surprisingly short time frame of 2 days. Intranasal inoculation in postnatal day 14 mice with VSVΔG-CHIKV or VLV evoked no adverse response, whereas VSVΔG-H5N1 by this route was lethal in most mice. A key immune mechanism underlying the safety of VSVΔG-CHIKV, VSVΔG-H5N1, and VLV in the adult brain was the type I interferon response; all three viruses were lethal in the brains of adult mice lacking the interferon receptor, suggesting that the viruses can infect and replicate and spread in brain cells if not blocked by interferon-stimulated genes within the brain. IMPORTANCE Vesicular stomatitis virus (VSV) shows considerable promise both as a vaccine vector and as an oncolytic virus. The greatest limitation of VSV is that it is highly neurotropic and can be lethal within the brain. The neurotropism can be mostly attributed to the VSV G glycoprotein. Here, we test 4 chimeric viruses of VSV with glycoprotein genes from Nipah, chikungunya, and influenza viruses and nonstructural genes from Semliki Forest virus. Two of the four, VSVΔG-CHIKV and VLV, show substantially attenuated neurotropism and were safe in the healthy adult mouse brain. VSVΔG-H5N1 was safe in the adult brain but lethal in the younger brain. VSVΔG Nipah F+G was even more neurotropic than wild-type VSV, evoking a rapid lethal response in the adult brain. These results suggest that while chimeric VSVs show promise, each must be tested with both intranasal and intracranial administration to ensure the absence of lethal neurotropism.

scholarly journals Spatiotemporal Expression and Molecular Characterization ofmiR-344bandmiR-344cin the Developing Mouse Brain

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Jia-Wen Leong ◽  
Syahril Abdullah ◽  
King-Hwa Ling ◽  
Pike-See Cheah
Keyword(s):  
Mouse Brain ◽  
Noncoding Rna ◽  
Granular Layer ◽  
Developmental Stages ◽  
Adult Brain ◽  
Stem Loop ◽  
Small Noncoding Rna ◽  
Spatiotemporal Expression ◽  
Developing Mouse Brain

MicroRNAs (miRNAs) are small noncoding RNA known to regulate brain development. The expression of two novel miRNAs, namely,miR-344bandmiR-344c, was characterized during mouse brain developmental stages in this study.In situhybridization analysis showed thatmiR-344bandmiR-344cwere expressed in the germinal layer during embryonic brain developmental stages. In contrast,miR-344bwas not detectable in the adult brain whilemiR-344cwas expressed exclusively in the adult olfactory bulb and cerebellar granular layer. Stem-loop RT-qPCR analysis of whole brain RNAs showed that expression of themiR-344bandmiR-344cwas increased as brain developed throughout the embryonic stage and maintained at adulthood. Further investigation showed that these miRNAs were expressed in adult organs, wheremiR-344bandmiR-344cwere highly expressed in pancreas and brain, respectively. Bioinformatics analysis suggestedmiR-344bandmiR-344ctargetedOlig2andOtx2mRNAs, respectively. However, luciferase experiments demonstrated that these miRNAs did not targetOlig2andOtx2mRNAs. Further investigation on the locality ofmiR-344bandmiR-344cshowed that both miRNAs were localized in nuclei of immature neurons. In conclusion,miR-344bandmiR-344cwere expressed spatiotemporally during mouse brain developmental stages.

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