scholarly journals Kinetics of alpha-synuclein depletion in three brain regions following conditional pan-neuronal inactivation of the encoding gene (Snca) by tamoxifen-induced Cre-recombination in adult mice

2021 ◽  
Author(s):  
Kirill D. Chaprov ◽  
Ekaterina A. Lysikova ◽  
Ekaterina V. Teterina ◽  
Vladimir L. Buchman
Keyword(s):  
Cerebral Cortex ◽  
Neuron Specific Enolase ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Tamoxifen Treatment ◽  
Adult Mice ◽  
Cre Recombination ◽  
Lag Period ◽  
Kinetics Of ◽  
Old Mice

AbstractConditional pan-neuronal inactivation of the Snca gene in 2-month old male and female mice causes dramatic decrease in the level of the encoded protein, alpha-synuclein, in three studied brain regions, namely cerebral cortex, midbrain and striatum, 12 weeks after the last injection of tamoxifen. Kinetics of alpha-synuclein depletion is different in these brain regions with a longer lag period in the cerebral cortex where this protein is normally most abundant. Our results suggest that efficient post-developmental pan-neuronal knockout of alpha-synuclein in adult, i.e. 5- to 6-month old, animals, could be achieved by tamoxifen treatment of 2-month old mice carrying loxP-flanked Snca gene and expressing inducible Cre-ERT2 recombinase under control of the promoter of neuron-specific enolase (NSE) gene.

scholarly journals Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice

2020 ◽  
Vol 133 (3) ◽  
pp. 595-610 ◽  
Author(s):  
Yang Yu ◽  
Yongyan Yang ◽  
Hong Tan ◽  
Myriam Boukhali ◽  
Ashok Khatri ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Tau Phosphorylation ◽  
Mitochondrial Metabolism ◽  
Sevoflurane Anesthesia ◽  
Neonatal Mice ◽  
Adult Mice ◽  
Baseline Conditions ◽  
Old Mice

Background Sevoflurane anesthesia induces Tau phosphorylation and cognitive impairment in neonatal but not in adult mice. This study tested the hypothesis that differences in brain Tau amounts and in the activity of mitochondria–adenosine triphosphate (ATP)–Nuak1–Tau cascade between the neonatal and adult mice contribute to the age-dependent effects of sevoflurane on cognitive function. Methods 6- and 60-day-old mice of both sexes received anesthesia with 3% sevoflurane for 2 h daily for 3 days. Biochemical methods were used to measure amounts of Tau, phosphorylated Tau, Nuak1, ATP concentrations, and mitochondrial metabolism in the cerebral cortex and hippocampus. The Morris water maze test was used to evaluate cognitive function in the neonatal and adult mice. Results Under baseline conditions and compared with 60-day-old mice, 6-day-old mice had higher amounts of Tau (2.6 ± 0.4 [arbitrary units, mean ± SD] vs. 1.3 ± 0.2; P < 0.001), Tau oligomer (0.3 ± 0.1 vs. 0.1 ± 0.1; P = 0.008), and Nuak1 (0.9 ± 0.3 vs. 0.3 ± 0.1; P = 0.025) but lesser amounts of ATP (0.8 ± 0.1 vs. 1.5 ± 0.1; P < 0.001) and mitochondrial metabolism (74.8 ± 14.1 [pmol/min] vs. 169.6 ± 15.3; P < 0.001) in the cerebral cortex. Compared with baseline conditions, sevoflurane anesthesia induced Tau phosphorylation at its serine 202/threonine 205 residues (1.1 ± 0.4 vs. 0.2 ± 0.1; P < 0.001) in the 6-day-old mice but not in the 60-day-old mice (0.05 ± 0.04 vs. 0.03 ± 0.01; P = 0.186). The sevoflurane-induced Tau phosphorylation and cognitive impairment in the neonatal mice were both attenuated by the inhibition of Nuak1 and the treatment of vitamin K2. Conclusions Higher brain Tau concentrations and lower brain mitochondrial metabolism in neonatal compared with adult mice contribute to developmental stage–dependent cognitive dysfunction after sevoflurane anesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Ischemia Induces Release of Endogenous Amino Acids from the Cerebral Cortex and Cerebellum of Developing and Adult Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Simo S. Oja ◽  
Pirjo Saransaari
Keyword(s):  
Amino Acids ◽  
Cerebral Cortex ◽  
Gaba Release ◽  
Taurine Release ◽  
Adult Mice ◽  
High K ◽  
Old Mice ◽  
Harmful Effects ◽  
Cortical Slices ◽  
Developing Mice

Ischemia enhanced release of endogenous neuroactive amino acids from cerebellar and cerebral cortical slices. More glutamate was released in adult than developing mice. Taurine release enhanced by K+ stimulation and ischemia was more than one magnitude greater than that of GABA or glutamate in the developing cerebral cortex and cerebellum, while in adults the releases were almost comparable. Aspartate release was prominently enhanced by both ischemia and K+ stimulation in the adult cerebral cortex. In the cerebellum K+ stimulation and ischemia evoked almost 10-fold greater GABA release in 3-month olds than in 7-day olds. The release of taurine increased severalfold in the cerebellum of 7-day-old mice in high-K+ media, whereas the K+-evoked effect was rather small in adults. In 3-month-old mice no effects of K+ stimulation or ischemia were seen in the release of aspartate, glycine, glutamine, alanine, serine, or threonine. The releases from the cerebral cortex and cerebellum were markedly different and also differed between developing and adult mice. In developing mice only the release of inhibitory taurine may be large enough to counteract the harmful effects of excitatory amino acids in ischemia in both cerebral cortex and cerebellum, in particular since at that age the release of glutamate and aspartate cannot be described as massive.

scholarly journals The Importation of Hematogenous Precursors by the Thymus Is a Gated Phenomenon in Normal Adult Mice

2001 ◽  
Vol 193 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Deborah L. Foss ◽  
Elina Donskoy ◽  
Irving Goldschneider
Keyword(s):  
Adult Life ◽  
Normal Adult ◽  
New Paradigm ◽  
Intravenous Injections ◽  
Adult Mice ◽  
Gate Opening ◽  
Age Dependent ◽  
Intrathymic Injection ◽  
Kinetics Of ◽  
Old Mice

Hematogenous precursors repopulate the thymus of normal adult mice, but it is not known whether this process is continuous or intermittent. Here, two approaches were used to demonstrate that the importation of prothymocytes in adult life is a gated phenomenon. In the first, age-dependent receptivity to thymic chimerism was studied in nonirradiated Ly 5 congenic mice by quantitative intrathymic and intravenous bone marrow (BM) adoptive transfer assays. In the second, the kinetics of importation of blood-borne prothymocytes was determined by timed separation of parabiotic mice. The results showed that >60% of 3–18-wk-old mice developed thymic chimerism after intrathymic injection of BM cells, and that the levels of chimerism (range, 5–90% donor-origin cells) varied cyclically (periodicity, 3 to 5 wk). In contrast, only 11–14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period ∼1 wk; refractory period ∼3 wk). In the intravenously injected mice, chimerism occurred simultaneously in both thymic lobes; gate opening occurred only after most intrathymic niches for prothymocytes had emptied; and the ensuing wave of thymocytopoiesis encompassed two periods of gating. These kinetics were confirmed in parabiotic mice, and in cohorts of mice in whom gating was synchronized by an initial intrathymic injection of BM cells. In addition, a protocol was developed by which sequential intravenous injections of BM cells over a 3 to 4 wk period routinely induces thymic chimerism in the apparent absence of stem cell chimerism. Hence, the results not only provide a new paradigm for the regulation of prothymocyte importation during adult life, but may also have applied implications for the selective induction of thymocytopoiesis in nonmyeloablated hosts.

scholarly journals Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ravi L. Rungta ◽  
Marc Zuend ◽  
Ali-Kemal Aydin ◽  
Éric Martineau ◽  
Davide Boido ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Somatosensory Cortex ◽  
Cerebral Blood Volume ◽  
Transfer Functions ◽  
Neurovascular Coupling ◽  
Sensory Stimulation ◽  
Brain Regions ◽  
Blood Velocity ◽  
Functional Brain Imaging ◽  
Vascular Events

AbstractThe spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.

scholarly journals STABILITY OF DNA IN PURKINJE CELL NUCLEI OF THE MOUSE

1974 ◽  
Vol 63 (2) ◽  
pp. 665-674 ◽  
Author(s):  
V. Mareš ◽  
B. Schultze ◽  
W. Maurer
Keyword(s):  
Young Adult ◽  
Purkinje Cell ◽  
Nuclear Dna ◽  
Brain Regions ◽  
Nuclear Volume ◽  
High Dose ◽  
Prenatal Period ◽  
Cell Nuclei ◽  
Grain Number ◽  
Adult Mice

Neurons of the mouse were labeled with [3H]thymidine during their prenatal period of proliferation. The 3H activity of the Purkinje cell nuclei was then studied autoradiographically 8, 25, 55, and 90 days after birth. The measured grain number per nucleus decreased by about 14% between the 8th and 25th postnatal days and then remained constant up to 90 days. There was no significant decrease of the 3H activity of the Purkinje cell nuclei after correction of the measured grain number per nucleus for increasing nuclear volume of the growing Purkinje cells and for the influence of [3H]ß self-absorption in the material of the sections. Injection of a high dose of [3H]thymidine into young adult mice did not result in 3H labeling of either Purkinje or other neurons in other brain regions. The results agree with the concept of metabolic stability of nuclear DNA. "Metabolic" DNA could not be observed in these experiments.

Abstract WMP41: Neuronal Sirt1 is Required for Resveratrol Preconditioning Induced Ischemic Tolerance

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kevin B Koronowski ◽  
Isa Saul ◽  
Zachary Balmuth-Loris ◽  
Miguel Perez-Pinzon
Keyword(s):  
Knockout Mouse ◽  
Infarct Volume ◽  
Hypoxia Inducible Factor ◽  
Brain Regions ◽  
Artery Occlusion ◽  
Ischemic Tolerance ◽  
Tamoxifen Treatment ◽  
Neurological Score ◽  
Transcription Factor Activation ◽  
Cerebral Artery Occlusion

Introduction: Our previous work demonstrates that resveratrol, a naturally occurring polyphenol, protects against cerebral ischemia when administered 2 or 14 days prior to injury. Resveratrol activates Sirt1, an NAD + -dependent deacylase that regulates cellular metabolism. It has been postulated that neuronal Sirt1 directly mediates this neuroprotection but it remains to be empirically tested. Objective: The objective of this study was to generate an inducible, neuronal-specific Sirt1 knockout mouse and determine whether neuronal Sirt1 is necessary for resveratrol-induced ischemic tolerance. Methods: Twenty to twenty-five gram neuronal-specific Sirt1 knockout mice (Sirt1neu-/-) and WTs were induced with tamoxifen. Mice were randomized for 1) western blot; 2) resveratrol preconditioning (RPC; 10 mg/kg resveratrol i.p.) or vehicle (1.5% DMSO; 0.9% saline) treatment 2 days prior to 60 minute middle cerebral artery occlusion (MCAo); 3) untargeted primary metabolomics by GC-TOF-MS; or 4) transcription factor activation profiling. Twenty-four hours following MCAo, neurological score was used to assess functional outcome and infarct volume was quantified by TTC staining. Results: Tamoxifen treatment removed WT Sirt1 protein from major brain regions but not from heart (Figure 1A, n=3). In WT, RPC reduced infarct volume by 43.7% and improved neurological score by nearly 3 points, however these effects were lost in Sirt1neu-/- (Figure 1B, n=5-9). Compared to WT, metabolic profiles from Sirt1neu-/- displayed significantly altered glycolysis metabolites (Figure 1C, n=8). Activation of hypoxia inducible factor (HIF) was reduced by 48% in Sirt1neu-/- (Figure 1D, n=3). Conclusions: We generated and utilized an inducible, neuronal-specific knockout mouse to demonstrate that neuronal Sirt1 specifically is required for RPC-induced ischemic tolerance. Additionally, Sirt1 regulates glycolysis in the brain, possibly through its interaction with HIF.

Brain regions susceptible to alpha-synuclein spreading

2021 ◽  
Author(s):  
Yu-Jie Guo ◽  
Huan Xiong ◽  
Kang Chen ◽  
Jin-Jun Zou ◽  
Peng Lei
Keyword(s):  
Brain Regions ◽  
Alpha Synuclein

scholarly journals The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid

2021 ◽  
Vol 15 ◽  
Author(s):  
Kazuhiko Sawada ◽  
Shiori Kamiya ◽  
Ichio Aoki
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Magnetic Resonance ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
S100 Protein ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Magnetic Resonance Images ◽  
Neonatal Exposure

Prenatal and neonatal exposure to valproic acid (VPA) is associated with human autism spectrum disorder (ASD) and can alter the development of several brain regions, such as the cerebral cortex, cerebellum, and amygdala. Neonatal VPA exposure induces ASD-like behavioral abnormalities in a gyrencephalic mammal, ferret, but it has not been evaluated in brain regions other than the cerebral cortex in this animal. This study aimed to facilitate a comprehensive understanding of brain abnormalities induced by developmental VPA exposure in ferrets. We examined gross structural changes in the hippocampus and tracked proliferative cells by 5-bromo-2-deoxyuridine (BrdU) labeling following VPA administration to ferret infants on postnatal days (PDs) 6 and 7 at 200 μg/g of body weight. Ex vivo short repetition time/time to echo magnetic resonance imaging (MRI) with high spatial resolution at 7-T was obtained from the fixed brain of PD 20 ferrets. The hippocampal volume estimated using MRI-based volumetry was not significantly different between the two groups of ferrets, and optical comparisons on coronal magnetic resonance images revealed no differences in gross structures of the hippocampus between VPA-treated and control ferrets. BrdU-labeled cells were observed throughout the hippocampus of both two groups at PD 20. BrdU-labeled cells were immunopositive for Sox2 (>70%) and almost immunonegative for NeuN, S100 protein, and glial fibrillary acidic protein. BrdU-labeled Sox2-positive progenitors were abundant, particularly in the subgranular layer of the dentate gyrus (DG), and were denser in VPA-treated ferrets. When BrdU-labeled Sox2-positive progenitors were examined at 2 h after the second VPA administration on PD 7, their density in the granular/subgranular layer and hilus of the DG was significantly greater in VPA-treated ferrets compared to controls. The findings suggest that VPA exposure to ferret infants facilitates the proliferation of DG progenitors, supplying excessive progenitors for hippocampal adult neurogenesis to the subgranular layer.

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