Browsing by Subject "regeneration"

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  • Licht, Tamar; Kreisel, Tirzah; Biala, Yoav; Mohan, Sandesh; Yaari, Yoel; Anisimov, Andrey; Alitalo, Kari; Keshet, Eli (2020)
    Multiple insults to the brain lead to neuronal cell death, thus raising the question to what extent can lost neurons be replenished by adult neurogenesis. Here we focused on the hippocampus and especially the dentate gyrus (DG), a vulnerable brain region and one of the two sites where adult neuronal stem cells (NSCs) reside. While adult hippocampal neurogenesis was extensively studied with regard to its contribution to cognitive enhancement, we focused on their underestimated capability to repair a massively injured, nonfunctional DG. To address this issue, we inflicted substantial DG-specific damage in mice of either sex either by diphtheria toxin-based ablation of >50% of mature DG granule cells (GCs) or by prolonged brain-specific VEGF overexpression culminating in extensive, highly selective loss of DG GCs (thereby also reinforcing the notion of selective DG vulnerability). The neurogenic system promoted effective regeneration by increasing NSCs proliferation/survival rates, restoring a nearly original DG mass, promoting proper rewiring of regenerated neurons to their afferent and efferent partners, and regaining of lost spatial memory. Notably, concomitantly with the natural age-related decline in the levels of neurogenesis, the regenerative capacity of the hippocampus also subsided with age. The study thus revealed an unappreciated regenerative potential of the young DG and suggests hippocampal NSCs as a critical reservoir enabling recovery from catastrophic DG damage.
  • Kulha, Niko Aleksi; Pasanen, Leena; Holmström, Lasse; Grandpre, Louis de; Kuuluvainen, Timo Tapio; Aakala, Tuomas (2019)
    Identifying the scales of variation in forest structures and the underlying processes are fundamental for understanding forest dynamics. Here, we studied these scale-dependencies in forest structure in naturally dynamic boreal forests on two continents. We identified the spatial scales at which forest structures varied, and analyzed how the scales of variation and the underlying drivers differed among the regions and at particular scales. We studied three 2kmx2km landscapes in northeastern Finland and two in eastern Canada. We estimated canopy cover in contiguous 0.1-ha cells from aerial photographs and used scale-derivative analysis to identify characteristic scales of variation in the canopy cover data. We analyzed the patterns of variation at these scales using Bayesian scale space analysis. We identified structural variation at three spatial scales in each landscape. Among landscapes, the largest scale of variation showed the greatest variability (20.1-321.4ha), related to topography, soil variability, and long-term disturbance history. Superimposed on this large-scale variation, forest structure varied at similar scales (1.3-2.8ha) in all landscapes. This variation correlated with recent disturbances, soil variability, and topographic position. We also detected intense variation at the smallest scale analyzed (0.1ha, grain of our data), partly driven by recent disturbances. The distinct scales of variation indicated hierarchical structure in the landscapes studied. Except for the large-scale variation, these scales were remarkably similar among the landscapes. This suggests that boreal forests may display characteristic scales of variation that occur somewhat independent of the tree species characteristics or the disturbance regime.
  • Lalowski, Maciej M.; Björk, Susann; Finckenberg, Piet; Soliymani, Rabah; Tarkia, Miikka; Calza, Giulio; Blokhina, Daria; Tulokas, Sari; Kankainen, Matti; Lakkisto, Päivi; Baumann, Marc; Kankuri, Esko; Mervaala, Eero (2018)
    The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and beta-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.
  • Jenkins, Cherie (Helsingin yliopisto, 2020)
    Reptiles have long been studied in search of the mechanisms behind neuronal regeneration. This thesis delves into the regenerative areas of two emerging model species to the field of regenerative research: Pogona vitticeps (bearded dragon) and Pantherophis guttatus (corn snake). This fluorescent immunohistochemical study maps out and compares the constitutive proliferative zones in these two species to better define the focus of future comparative neurodegenerative experiments. A BrdU pulse chase experiment in conjunction with PCNA reveals proliferative zones in the lateral ventricular ependyma of both species. Stem cell niches were found in the ependymal lining adjacent to the medial cortex and dorsal ventricular ridge in both species, however, the nucleus sphericus ependyma was an active proliferative zone only in Pantherophis. Imaging of further markers in this study support the findings of the pulse chase experiment. High levels of the stem cell marker Sox2 was found in lateral ventricular ependymal cells in both species. The glial marker GFAP reveals a highly ordered array of radial glia in the cortical areas of Pogona, which is significantly reduced or absent in Pantherophis. And lastly the neuronal marker HU was found in the same cells that were BrdU positive and had migrated a short distance from the proliferative zones, which shows that the proliferative areas in the lateral ventricular lining do indeed produce neurons. The BrdU and PCNA marked cells were quantified in both species, and a brief comparison between the species showed that Pogona had a significantly higher number and concentration of proliferative cells in the proliferative zones than Pantherophis. Scattered BrdU positive cells that were neither neuronal nor positive for any other marker were also found scattered throughout the parenchyma of Pogona, and these cells remain uncharacterized. Differences between these two species are not surprising, as lizards are known to have better regenerative capabilities than snakes, however, more comparative research between these species is needed to gain further insight into the mechanisms behind their contrasting regenerative capabilities.
  • Salminen, Ella (Helsingin yliopisto, 2020)
    The axolotl (Ambystoma mexicanum) has an astounding ability to regenerate entire lost body parts throughout its life. Significant progress has been made in recent years to understand the mechanisms of axolotl regeneration, but how the animal maintains its capacity for successful regeneration remains obscure. In mammals, the ability to repair damaged tissue drastically declines with age, in part due to the accumulation of senescent cells. However, in axolotls, the number of senescent cells does not increase upon aging. Low levels of chronic senescence in axolotls have been proposed to support their ability to regenerate even at an old age. Axolotls can efficiently clear senescent cells, but whether they can prevent the induction of senescence is not known. This thesis provides the first indication of a secreted anti-senescence activity from axolotl cells. Data presented here show that conditioned medium from cultured axolotl cells reduces senescence and increases proliferation in mouse embryonic fibroblast, a widely used model for spontaneous senescence. Remarkably, conditioned media from other tested cell types, namely cervical cancer cells and young mouse embryonic fibroblasts, did not considerably affect senescence, despite extensively increasing proliferation. Taken together, secreted factors from cultured axolotl cells seem to reduce senescence directly, and not by merely promoting proliferation. This observation forms a basis for future endeavors to determine whether preventing senescence facilitates regeneration in vivo.
  • Kubin, Eero; Kemppainen, Lauri (The Society of Forestry in Finland - The Finnish Forest Research Institute, 1994)
    The effect of scarification, ploughing and cross-directional plouhing on temperature conditions in the soil and adjacent air layer have been studied during 11 consecutive growth periods by using an unprepared clear-cut area as a control site. The maximum and minimum temperatures were measured daily in the summer months, and other temperature observations were made at four-hour intervals by means of a Grant measuring instrument. The development of the seedling stand was also followed in order to determine its shading effect on the soil surface. Soil preparation decreased the daily temperature amplitude of the air at the height of 10 cm. The maximum temperatures on sunny days were lower in the tilts of the ploughed and in the humps of the cross-directional ploughed sites compared with the unprepared area. Correspondingly, the night temperatures were higher and so the soil preparation considerably reduced the risk of night frost. In the soil at the depth of 5 cm, soil preparation increased daytime temperatures and reduced night temperatures compared with unprepared area. The maximum increase in monthly mean temperatures was almost 5 °C, and the daily variation in the surface parts of the tilts and humps increased so that excessively high temperatures for the optimal growth of the root system were measured from time to time. The temperature also rose at the depths of 50 and 100 cm. Soil preparation also increased the cumulative temperature sum. The highest sums accumulated during the summer months were recorded at the depth of 5 cm in the humps of cross-directional ploughed area (1127 dd.) and in the tilts of the ploughed area (1106 dd.), while the corresponding figure in the unprepared soil was 718 dd. At the height of 10 cm the highest temperature sum was 1020 dd. in the hump, the corresponding figure in the unprepared area being 925 dd. The incidence of high temperature amplitudes and percentage of high temperatures at the depth of 5 cm decreased most rapidly in the humps of cross-directional ploughed area and in the ploughing tilts towards the end of the measurement period. The decrease was attributed principally to the compressing of tilts, the ground vegetation succession and the growth of seedlings. The mean summer temperature in the unprepared area was lower than in the prepared area and the difference did not diminish during the period studied. The increase in temperature brought about by soil preparation thus lasts at least more than 10 years.
  • Danilova, Tatiana; Lindahl, Maria (2018)
    Mesencephalic astrocyte-derived neurotrophic factor (MANF) was originally identified as a secreted trophic factor for dopamine neurons in vitro. It protects and restores damaged cells in rodent models of Parkinson's disease, brain and heart ischemia, spinocerebellar ataxia and retina in vivo. However, its exact mechanism of action is not known. MANF is widely expressed in most human and mouse organs with high levels in secretory tissues. Intracellularly, MANF localizes to the endoplasmic reticulum (ER) and ER stress increases it's expression in cells and tissues. Furthermore, increased MANF levels has been detected in the sera of young children with newly diagnosed Type 1 (T1D) diabetes and Type 2 (T2D) diabetic patients. ER stress is caused by the accumulation of misfolded and aggregated proteins in the ER. It activates a cellular defense mechanism, the unfolded protein response (UPR), a signaling cascade trying to restore ER homeostasis. However, if prolonged, unresolved ER stress leads to apoptosis. Unresolved ER stress contributes to the progressive death of pancreatic insulin-producing beta cells in both T1D and T2D. Diabetes mellitus is characterized by hyperglycemia, caused by the inability of the beta cells to maintain sufficient levels of circulating insulin. The current medications, insulin and antidiabetic drugs, alleviate diabetic symptoms but cannot reconstitute physiological insulin secretion which increases the risk of devastating vascular complications of the disease. Thus, one of the main strategies in improving current diabetes therapy is to define and validate novel approaches to protect beta cells from stress as well as activate their regeneration. Embryonic deletion of the Manf gene in mice led to gradual postnatal development of insulin-deficient diabetes caused by reduced beta cell proliferation and increased beta cell death due to increased and sustained ER stress. In vitro, recombinant MANF partly protected mouse and human beta cells from ER stress-induced beta cell death and potentiated mouse and human beta cell proliferation. Importantly, in vivo overexpression of MANF in the pancreas of T1D mice led to increased beta cell proliferation and decreased beta cell death, suggesting that MANF could be a new therapeutic candidate for beta cell protection and regeneration in diabetes.
  • Vaartaja, Olli (Suomen metsätieteellinen seura, 1955)
  • Eymann, Julia; Di-Poi, Nicolas (2020)
    The retina is a complex tissue responsible for both detection and primary processing of visual stimuli. Although all vertebrate retinas share a similar, multi-layered organization, the ability to regenerate individual retinal cells varies tremendously, being extremely limited in mammals and birds when compared to anamniotes such as fish and amphibians. However, little is yet known about damage response and regeneration of retinal tissues in "non-classical" squamate reptiles (lizards, snakes), which occupy a key phylogenetic position within amniotes and exhibit unique regenerative features in many tissues. Here, we address this gap by establishing and characterizing a model of excitotoxic retinal damage in bearded dragon lizard (Pogona vitticeps). We particularly focus on identifying, at the cellular and molecular level, a putative endogenous cellular source for retinal regeneration, as diverse self-repair strategies have been characterized in vertebrates using a variety of retinal injury and transgenic models. Our findings reveal for the first time that squamates hold the potential for postnatal retinal regeneration following acute injury. Although no changes occur in the activity of physiologically active progenitors recently identified at the peripheral retinal margin of bearded dragon, two distinct successive populations of proliferating cells at central retina respond to neurotoxin treatment. Following an initial microglia response, a second source of proliferating cells exhibit common hallmarks of vertebrate Muller glia (MG) activation, including cell cycle re-entry, dedifferentiation into a progenitor-like phenotype, and re-expression of proneural markers. The observed lizard glial responses, although not as substantial as in anamniotes, appear more robust than the absent or neonatal-limited regeneration reported without exogenous stimulation in other amniotes. Altogether, these results help to complete our evolutionary understanding of regenerative potential of the vertebrate retina, and further highlight the major importance of glial cells in retinal regeneration. Furthermore, our work offers a new powerful vertebrate model to elucidate the developmental and evolutionary bases of retinal regeneration within amniotes. Such new understanding of self-repair mechanisms in non-classical species endowed with regenerative properties may help designing therapeutic strategies for vertebrate retinal diseases.
  • Lappi, J.; Smolander, H.; Kotisaari, A. (Suomen metsätieteellinen seura, 1983)
  • Kellomäki, Seppo; Hänninen, Heikki; Kolström, Taneli (Suomen metsätieteellinen seura, 1988)
  • Tulokas, Sari (Helsingfors universitet, 2016)
    This study compared proliferation rate and expression of cardiac stem cell markers in one day seven days old mice hearts (1D and 7D). Primary antibodies Ki-67 and C-kit were used in immunohistochemistry and primers C-kit, GATA-4, Myh6, Sca-1 and Mesp1 were used in quantitative PCR. This study found a considerably higher proliferation rate and a higher number of C-kit+ stem cells in 1D than in 7D samples, but the difference was not statistically significant due to a small sample size. A significant difference in the expression of other studied markers was not found. These findings suggest that a decrease in proliferation rate and the number of C-kit+ stem cells coincide with the loss of regenerative potential. Therefore, it is possible that either, or both, of these changes are responsible for the closure of the regenerative window.
  • Kalervo, Karri (Helsingfors universitet, 2016)
    Sydämen regeneraatiokyky on ihmisellä hyvin rajallinen. Uusia sydänlihassoluja tiedetään muodostuvan jatkuvasti, mutta ei kuitenkaan riittävästi, jotta tuhoutuneen sydänlihaksen korjaantuminen esimerkiksi sydäninfarktin jälkeen olisi tehokasta. Tällä hetkellä ei ole kunnollisia keinoja, joilla voisi korjata jo syntyneitä vaurioita; terapeuttisilla menetelmillä voidaan lähinnä estää uusien vaurioiden syntyä. Hemioksygenaasi-1-entsyymillä (HO-1) tiedetään olevan edullisia vaikutuksia sydämen regeneraatiossa. Tutkimme seeprakalan sydämen kryovauriomallilla HO-1:n merkitystä sydämen regeneraatiossa. Neonataalirotan sydänlihassolujen avulla tutkittiin HO-1:n vaikutusta solujen proliferaatioon. Osoitimme HO-1:n indusoimisen parantavan seeprakalan sydämen funktiota vaurion jälkeen ja lisäävän uusien sydänlihassolujen määrää. Soluviljelymallissa HO-1:n indusointi lisää niin ikään uusien sydänlihassolujen määrää, toisaalta vaikuttaa siltä, että se myös estää proliferaatiota. HO-1 on mielenkiintoinen kohdemolekyyli etsittäessä uusia keinoja sydämen vaurioiden ja niistä seuraavan vajaatoiminnan hoitoon.
  • Sirén, Gustaf (Suomen metsätieteellinen seura, 1955)
  • Piha, Aura (Helsingfors universitet, 2011)
    Fire is an important driver of the boreal forest ecosystem, and a useful tool for the restoration of degraded forests. However, we lack knowledge on the ecological processes initiated by prescribed fires, and whether they bring about the desired restoration effects. The purpose of this study was to investigate the impacts of low-intensity experimental prescribed fires on four ecological processes in young commercial Scots pine (Pinus sylvestris) stands eight years after the burning. The processes of interest were tree mortality, dead wood creation, regeneration and fire scar formation. These were inventoried in twelve study plots, which were 30 m x 30 m in size. The plots belonged to two different stand age classes: 30-35 years or 45 years old at the time of burning. The study was partly a follow-up of study plots researched by Sidoroff et al. (2007) one year after burning in 2003. Tree mortality increased from 183 stems ha-1 in 2003 to 259 stems ha-1 in 2010, corresponding to 15 % and 21 % of stem number respectively. Most mortality was experienced in the stands of the younger age class, in smaller diameter classes and among species other than Scots pine. By 2010, the average mortality of Scots pine per plot was 18%, but varied greatly ranging from 0% to 63% of stem number. Delayed mortality, i.e. mortality that occurred between 2 and 8 years after fire, seemed to become more important with increasing diameter. The input of dead wood also varied greatly between plots, from none to 72 m3 ha-1, averaging at 12 m3 ha-1. The amount of fire scarred trees per plot ranged from none to 20 %. Four out of twelve plots (43 %) did not have any fire scars. Scars were on average small: 95% of scars were less than 4 cm in width, and 75% less than 40 cm in length. Owing to the light nature of the fire, the remaining overstorey and thick organic layer, regeneration was poor overall. The abundance of pine and other seedlings indicated a viable seed source existed, but the seedlings failed to establish under dense canopy. The number of saplings ranged from 0 to 12 333 stems ha-1. The results of this study indicate that a low intensity fire does not necessarily initiate the ecological processes of tree mortality, dead wood creation and regeneration in the desired scale. Fire scars, which form the basis of fire dating in fire history studies, did not form in all cases.