Endocytic BDNF secretion regulated by Vamp3 in astrocytes

Brain-derived neurotrophic factor (BDNF) regulates diverse brain functions via TrkB receptor signaling. Due to the expression of TrkB receptors, astrocytes can internalize extracellular BDNF proteins via receptor-mediated endocytosis. Endocytosed BDNF can be re-secreted upon stimulation, but the molecular mechanism underlying this phenomenon remains unrecognized. Our study reveals that vesicle-associated membrane protein 3 (Vamp3) selectively regulates the release of endocytic BDNF from astrocytes. By using quantum dot (QD)-conjugated mature BDNF (QD-BDNF) as a proxy for the extracellular BDNF protein, we monitored the uptake, transport, and secretion of BDNF from cultured cortical astrocytes. Our data showed that endocytic QD-BDNF particles were enriched in Vamp3-containing vesicles in astrocytes and that ATP treatment sufficiently triggered either the antero- or retrograde transport and exocytosis of QD-BDNF-containing vesicles. Downregulation of Vamp3 expression disrupted endocytic BDNF secretion from astrocytes but did not affect uptake or transport. Collectively, these results provide evidence of the selective ability of astrocytic Vamp3 to control endocytic BDNF secretion during BDNF recycling. © 2021, The Author(s).1

Photobiomodulation with a 660-Nanometer Light-Emitting Diode Promotes Cell Proliferation in Astrocyte Culture

Astrocytes act as neural stem cells (NSCs) that have the potential to self-renew and differentiate into other neuronal cells. The protein expression of these astrocytes depends on the stage of differentiation, showing sequential expression of multiple proteins such as octamer-binding transcription factor 4 (Oct4), nestin, glial fibrillary acidic protein (GFAP), and aldehyde dehydrogenase 1 family member L1 (aldh1L1). Photobiomodulation (PBM) affects cell apoptosis, proliferation, migration, and adhesion. We hypothesized that astrocyte proliferation and differentiation would be modulated by PBM. We used an optimized astrocyte culture method and a 660-nanometer light-emitting diode (LED) to enhance the biological actions of many kinds of cells. We determined that the 660-nanometer LED promoted the biological actions of cultured astrocytes by increasing the reactive oxygen species levels. The overall viability of the cultured cells, which included various cells other than astrocytes, did not change after LED exposure; however, astrocyte-specific proliferation was observed by the increased co-expression of GFAP and bromodeoxyuridine (BrdU)/Ki67. Furthermore, the 660-nanometer LED provides evidence of differentiation, as shown by the decreased Oct4 and GFAP co-expression and increased nestin and aldh1L1 expression. These results demonstrate that a 660-nanometer LED can modify astrocyte proliferation, which suggests the efficacy of the therapeutic application of LED in various pathological states of the central nervous system

Effects of 660-nm LED photobiomodulation on drebrin expression pattern and astrocyte migration

Abstract Photobiomodulation (PBM) is a therapeutic tool that uses red or near-infrared light in medical applications. It’s applications in both central (CNS) and peripheral nervous system (PNS) are widely studied. Among glial cells, astrocytes are known to be activated in injured or damaged brains. Astrocytic cell migration is crucial for maintaining homeostasis in the brain. Our previous study showed that PBM led to astrocyte proliferation and differentiation, but the effects on migration has not been investigated. The aim of this study was to evaluate the effect of PBM on astrocyte migration, drebrin (DBN) expression and cytoplasmic morphology using primary cultured rat astrocyte. We applied a 660-nm light-emitting diode (LED) with fluence of 6, 12 and 18 J/cm2. PBM effects on astrocyte migration were analyzed by two different migration assays (scratch assay and transwell assay). We used immunofluorescence microscopy for visualizing DBN and glial-fibrillary acidic protein (GFAP) and analysis of DBN expression and astrocyte cytoplasmic morphology. Both scratch assay and transwell assay showed significant difference in astrocyte migration following PBM irradiation. With these specific fluence conditions, differences in DBN expression and cell morphology were revealed. PBM could increase the astrocyte migration by altering the cell morphology and DBN expression pattern

OR2AT4, an Ectopic Olfactory Receptor, Suppresses Oxidative Stress-Induced Senescence in Human Keratinocytes

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, Golfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated β-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKβ/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes

Optimal Trajectory Correction Maneuver Design Using the B-Plane Targeting Method for Future Korean Mars Missions

Optimal Trajectory Correction Maneuver (TCM) design algorithm has been developed using the B-plane targeting method for future Korean Mars missions. For every mission phase, trajectory informations can also be obtained using this developed algorithms which are essential to design optimal TCM strategy. The information were computed under minimum requiring perturbations to design Mars missions. Spacecraft can not be reached at designed aim point because of unexpected trajectory errors, caused by many perturbations and errors due to operating impulsive maneuvers during the cruising phase of missions. To maintain spacecraft's appropriate trajectory and deliver it to the designed aim point, B-plane targeting techniques are needed. A software NPSOL is used to solve this optimization problem, with the performance index of minimizing total amount of TCM's magnitude. And also executing time of maneuvers can be controlled for the user defined maneuver number (1˜5) of TCMs. The constraints, the Mars arrival B-plane boundary conditions, are formulated for the problem. Results of this work show the ability to design and analyze overall Mars missions, from the Earth launch phase to Mars arrival phase including capture orbit status for future Korean Mars missions

Korean Mars Mission Design Using KSLV-III

Mission opportunities and trajectory characteristics for the future Korean Mars mission have designed and analyzed using KSLV-III(Korea Space Launch Vehicle-III). Korea's first space center, ``NARO space center'' is selected as a launch site. For launch opportunities, year 2033 is investigated under considering the date of space center's completion with KSLV series development status. Optimal magnitude of various maneuvers, Trans Mars Injection (TMI) maneuver, Trajectory Correction Maneuver (TCM), Mars Orbit Insertion (MOI) maneuver and Orbit Trim Maneuver (OTM), which are required during the every Mars mission phases are computed with the formulation of nonlinear optimization problems using NPSOL software. Finally, mass budgets for upper stage (launcher) for KSLV-III and spacecraft are derived using various optimized maneuver magnitudes. For results, daily launch window from NARO space center for successful Korean Mars mission is avaliable for next 27 minutes starting from Apr. 16. 2033. 12:17:26 (UTC). Maximum spacecraft gross mass which can delivered to Mars is about 206 kg, with propellant mass of 109 kg and structure mass of 97 kg, when on board spacecraft thruster's Isp is assumed to have 290 sec. For upper stage, having structure ratio of 0.15 and Isp value of 280 sec, gross mass is about 1293 kg with propellant mass of 1099 kg and structure mass of 194 kg. However, including 10% margins to computed optimal maneuver values, spacecraft gross mass is reduced to about 148 kg with upper stage's mass of 1352 kg. This work will give various insights, requiring performances to developing of KSLV-III and spacecraft design for future Korean Mars missions

Dynamic Model Development for Interplanetary Navigation

In this paper, the dynamic model development for interplanetary navigation has been discussed. The Cowell method for special perturbation theories was employed to develop an interplanetary trajectory propagator including the perturbations due to geopotential, the Earth's dynamic polar motion, the gravity of the Sun, the Moon and the other planets in the solar system, the relativistic effect of the Sun, solar radiation pressure, and atmospheric drag. The equations of motion in dynamic model were numerically integrated using Adams-Cowell 11th order predictor-corrector method. To compare the influences of each perturbation, trajectory propagation was performed using initial transfer orbit elements of the Mars Express mission launched in 2003, because it can be the criterion to choose proper perturbation models for navigation upon required accuracy. To investigate the performance of dynamic model developed, it was tested whether the spacecraft can reach the Mars. The interplanetary navigation tool developed in this study demonstrated the spacecraft entering the Mars SOI(Sphere of Influence) and its velocity relative to the Mars was less than the escape velocity of the Mars, hence, the spacecraft can arrive at the target planet. The obtained results were also verified by using the AGI Satellite Tool Kit. It is concluded that the developed program is suitable for supporting interplanetary spacecraft mission for a future Korean Mars mission

An Orbit Propagation Software for Mars Orbiting Spacecraft

An orbit propagation software for the Mars orbiting spacecraft has been developed and verified in preparations for the future Korean Mars missions. Dynamic model for Mars orbiting spacecraft has been studied, and Mars centered coordinate systems are utilized to express spacecraft state vectors. Coordinate corrections to the Mars centered coordinate system have been made to adjust the effects caused by Mars precession and nutation. After spacecraft enters Sphere of Influence (SOI) of the Mars, the spacecraft experiences various perturbation effects as it approaches to Mars. Every possible perturbation effect is considered during integrations of spacecraft state vectors. The Mars50c gravity field model and the Mars-GRAM 2001 model are used to compute perturbation effects due to Mars gravity field and Mars atmospheric drag, respectively. To compute exact locations of other planets, JPL's DE405 ephemerides are used. Phobos and Deimos's ephemeris are computed using analytical method because their informations are not released with DE405. Mars Global Surveyor's mapping orbital data are used to verify the developed propagator performances. After one Martian day propagation (12 orbital periods), the results show about maximum ±5 meter errors, in every position state components(radial, cross-track and along-track), when compared to these from the Astrogator propagation in the Satellite Tool Kit. This result shows high reliability of the developed software which can be used to design near Mars missions for Korea, in future

Earth to Mars Ballistic Mission Opportunities from Naro Space Center

Earth to Mars ballistic mission opportunities from Naro Space Center are studied. Determining ballistic mission opportunities can be divided into two major parts, i.e. the launch window and the daily launch window determination. At the launch window determination parts, Porkchop diagrams of Earth launch C3 magnitude, total mission duration, declination of V∞ vector at the Earth launch, and declination & right ascension of V∞ vector at the Mars arrival are examined. The location of launch site and rotation effects of the Earth are considered during the daily launch window determination parts. Using Lambert method, various Porkchop diagrams of launching in 2027 are examined for example. The daily launch window of Naro Space Center at that year was checked to verify the launch possibility by comparing with the Kennedy Space Center

Launch Opportunities for Jupiter Missions Using the Gravity Assist

Interplanetary trajectories using the gravity assists are studied for future Korean interplanetary missions. Verifications of the developed softwares and results were performed by comparing data from ESA's Mars Express mission and previous results. Among the Jupiter exploration mission scenarios, multi-planet gravity assist mission to Jupiter (Earth-Mars-Earth-Jupiter Gravity Assist, EMEJGA trajectory) requires minimum launch energy (C3) of 29.231 km2/s2 with 4.6 years flight times. Others, such as direct mission and single-planet(Mars) gravity assist mission, requires launch energy (C3) of 75.656 km^2/s^2 with 2.98 years flight times and 63.590 km2/s2 with 2.33 years flight times, respectively. These results show that the planetary gravity assists can reduce launch energy, while EMEJGA trajectory requires the longer flight time than the other missions