Protein expression differs between neural progenitor cells from the adult rat brain subventricular zone and olfactory bulb

<p>Abstract</p> <p>Background</p> <p>Neural progenitor cells can be isolated from various regions of the adult mammalian brain, including the forebrain structures of the subventricular zone and the olfactory bulb. Currently it is unknown whether functional differences in these progenitor cell populations can already be found on the molecular level. Therefore, we compared protein expression profiles between progenitor cells isolated from the subventricular zone and the olfactory bulb using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry. The subventricular zone and the olfactory bulb are connected by the Rostral Migratory Stream (RMS), in which glial fibrillary acidic protein (GFAP)-positive cells guide neuroblasts. Recent literature suggested that these GFAP-positive cells possess neurogenic potential themselves. In the current study, we therefore compared the cultured neurospheres for the fraction of GFAP-positive cells and their morphology of over a prolonged period of time.</p> <p>Results</p> <p>We found significant differences in the protein expression patterns between subventricular zone and olfactory bulb neural progenitor cells. Of the differentially expressed protein spots, 105 were exclusively expressed in the subventricular zone, 23 showed a lower expression and 51 a higher expression in the olfactory bulb. The proteomic data showed that more proteins are differentially expressed in olfactory bulb progenitors with regard to proteins involved in differentiation and microenvironmental integration, as compared to the subventricular zone progenitors. Compared to 94% of all progenitors of the subventricular zone expressed GFAP, nearly none in the olfactory bulb cultures expressed GFAP. Both GFAP-positive subpopulations differed also in morphology, with the olfactory bulb cells showing more branching. No differences in growth characteristics such as doubling time, and passage lengths could be found over 26 consecutive passages in the two cultures.</p> <p>Conclusion</p> <p>In this study, we describe differences in protein expression of neural progenitor populations isolated from two forebrain regions, the subventricular zone and the olfactory bulb. These subpopulations can be characterized by differential expression of marker proteins. We isolated fractions of progenitor cells with GFAP expression from both regions, but the GFAP-positive cells differed in number and morphology. Whereas in vitro growth characteristics of neural progenitors are preserved in both regions, our proteomic and immunohistochemical data suggest that progenitor cells from the two regions differ in morphology and functionality, but not in their proliferative capacity.</p

Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

Self-organization of developing embryo using scale-invariant approach

<p>Abstract</p> <p>Background</p> <p>Self-organization is a fundamental feature of living organisms at all hierarchical levels from molecule to organ. It has also been documented in developing embryos.</p> <p>Methods</p> <p>In this study, a scale-invariant power law (SIPL) method has been used to study self-organization in developing embryos. The SIPL coefficient was calculated using a centro-axial skew symmetrical matrix (CSSM) generated by entering the components of the Cartesian coordinates; for each component, one CSSM was generated. A basic square matrix (BSM) was constructed and the determinant was calculated in order to estimate the SIPL coefficient. This was applied to developing <it>C. elegans </it>during early stages of embryogenesis. The power law property of the method was evaluated using the straight line and Koch curve and the results were consistent with fractal dimensions (fd). Diffusion-limited aggregation (DLA) was used to validate the SIPL method.</p> <p>Results and conclusion</p> <p>The fractal dimensions of both the straight line and Koch curve showed consistency with the SIPL coefficients, which indicated the power law behavior of the SIPL method. The results showed that the ABp sublineage had a higher SIPL coefficient than EMS, indicating that ABp is more organized than EMS. The fd determined using DLA was higher in ABp than in EMS and its value was consistent with type 1 cluster formation, while that in EMS was consistent with type 2.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Treatment and long-term outcome in primary distal renal tubular acidosis

Background Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome.Methods We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form.Results Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage 2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate.Conclusion Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.C1 [Lopez-Garcia, Sergio Camilo; Kleta, Robert; Bockenhauer, Detlef] NHS Fdn Trust, Great Ormond St Hosp Children, Dept Paediat Nephrol, London, England.[Lopez-Garcia, Sergio Camilo; Walsh, Stephen B.; Dufek, Stephanie; Iancu, Daniela; Kleta, Robert; Bockenhauer, Detlef] UCL, Ctr Nephrol, London, England.[Walsh, Stephen B.] Bambino Gesu Childrens Hosp IRCCS, Div Nephrol, Rome, Italy.[Fila, Marc] Montpellier Univ Hosp, CHU Arnaud Villeneuve, Pediat Nephrol, Montpellier, France.[Hooman, Nakysa] Iran Univ Med Sci, Ali Asghar Clin Res Dev Ctr, Tehran, Iran.[Zaniew, Marcin] Univ Zielona Gora, Dept Pediat, Zielona Gora, Poland.[Bertholet-Thomas, Aurelia] Ctr Reference Malad Renales Rares, Bron, France.[Colussi, Giacomo] ASST Niguarda, Milan, Italy.[Burgmaier, Kathrin] Univ Hosp Cologne, Dept Pediat, Cologne, Germany.[Levtchenko, Elena] Univ Hosp Leuven, Leuven, Belgium.[Sharma, Jyoti; Singhal, Jyoti] King Edward Mem Hosp, Pune, Maharashtra, India.[Soliman, Neveen A.] Cairo Univ, Dept Pediat, Ctr Pediat Nephrol & Transplantat, Kasr Al Ainy Sch Med, Cairo, Egypt.[Ariceta, Gema] Hosp Univ Vall dHebron, Barcelona, Spain.[Basu, Biswanath] NRS Med Coll, Div Pediat Nephrol, Kolkata, India.[Murer, Luisa] Azienda Osped & Univ Padova, Pediat Nephrol Dialysis & Transplant Unit, Padua, Italy.[Tasic, Velibor] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Tsygin, Alexey] Natl Med & Res Ctr Childrens Hlth, Moscow, Russia.[Decramer, Stephane] CHU Toulouse, Serv Nephrol Pediat, Hop Enfants, Ctr Reference Malad Renales Rares Sud Ouest, Toulouse, France.[Gil-Pena, Helena] Hosp Univ Cent Asturias, Oviedo, Spain.[Koster-Kamphuis, Linda] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.[La Scola, Claudio] Azienda Osped Univ St Orsola Malpighi, Nephrol & Dialysis Unit, Dept Woman Child & Urol Dis, Bologna, Italy.[Gellermann, Jutta; Thumfart, Julia] Charite Univ Med Berlin, Berlin, Germany.[Konrad, Martin; Koenig, Jens] Univ Childrens Hosp, Munster, Germany.[Lilien, Marc] Univ Med Ctr, Wilhelmina Childrens Hosp, Utrecht, Netherlands.[Francisco, Telma] Ctr Hosp Lisboa Cent, Lisbon, Portugal.[Tramma, Despoina] Aristotle Univ Thessaloniki, Pediat Dept 4, Thessaloniki, Greece.[Trnka, Peter] Lady Cilento Childrens Hosp, Brisbane, Qld, Australia.[Trnka, Peter; Mallett, Andrew] Univ Queensland, Sch Med, Brisbane, Qld, Australia.[Yuksel, Selcuk] Pamukkale Univ, Dept Pediat Nephrol, Sch Med, Denizli, Turkey.[Caruso, Maria Rosa] Azienda Osped Papa Giovani XXIII, Nephrol Unit, Bergamo, Italy.[Chromek, Milan] Lund Univ, Karolinska Inst, Lund, Sweden.[Ekinci, Zelal] Grp Florence Nightingale Hosp, Istanbul, Turkey.[Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Fdn Policlin A Gemelli, Rome, Italy.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Nephrol Ctr Excellence, Fac Med, Jeddah, Saudi Arabia.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Dept, Fac Med, Jeddah, Saudi Arabia.[Taroni, Francesca] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Pediat Nephrol Dialysis & Transplant Unit, Milan, Italy.[Trepiccione, Francesco] Univ Campania L Vanvitelli, Dept Translat Med Sci, Naples, Italy.[Winding, Louise] Lillebaelt Hosp Kolding, Pediat Dept, Kolding, Denmark.[Wuehl, Elke; Schaefer, Franz] Univ Hosp Heidelberg, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany.[Agbas, Ayse] Haseki Educ & Res Hosp, Istanbul, Turkey.[Belkevich, Anna] Belarusian State Med Univ, Minsk, BELARUS.[Vargas-Poussou, Rosa; Blanchard, Anne] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France.[Conti, Giovanni] AOU Policlin G Martino, Pediat Nephrol Unit, Messina, Italy.[Boyer, Olivia] Hop Necker Enfants Malad, Paris, France.[Dursun, Ismail; Pinarbasi, Ayse Seda] Erciyes Univ, Dept Pediat Nephrol, Fac Med, Kayseri, Turkey.[Melek, Engin] Cukurova Univ, Adana, Turkey.[Miglinas, Marius] Vilnius Univ, Nephrol Ctr, Santaros Klin, Vilnius, Lithuania.[Novo, Robert] Univ Hosp Lille, Lille, France.[Mallett, Andrew] Royal Brisbane & Womens Hosp, Dept Renal Med, Brisbane, Qld, Australia.[Milosevic, Danko] Univ Hosp Ctr Zagreb, Zagreb, Croatia.[Szczepanska, Maria] SUM Katowice, Dept Pediat, SMDZ Zabrze, Katowice, Poland.[Wente, Sarah] Hannover Med Sch, Dept Pediat Nephrol, Hannover, Germany.[Cheong, Hae Il] Seoul Univ, Dept Pediat, Childrens Hosp, Seoul, South Korea.[Sinha, Rajiv] Inst Child Hlth, Kolkata, India.[Gucev, Zoran] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Peco-Antic, Amira] Univ Childrens Hosp, Dept Nephrol, Belgrade, Serbia.[Kaur, Amrit] Royal Manchester Childrens Hosp, Dept Paediat Nephrol, Manchester, Lancs, England.[Paglialunga, Antonino] ASP Ragusa, Modica, Italy.[Servais, Aude] CHU Necker, APHP, Dept Nephrol, Paris, France.[Lutovac, Branko] Inst Childrens Dis, Clin Ctr Montenegro, Podgorica, Montenegro.[Hoorn, Ewout J.] Erasmus MC, Rotterdam, Netherlands.[Shasha-Lavsky, Hadas] Galilee Med Ctr, Nahariyya, Israel.[Harambat, Jerome; Godron-Dubrasquet, Astrid] Bordeaux Univ Hosp, Pediat Nephrol Unit, Bordeaux, France.[Buder, Kathrin] Univ Hosp Carl Gustav Carus Dresden, Pediat Dept, Dresden, Germany.[Allard, Lise] Angers Univ Hosp, Dept Pediat, Angers, France.[Patzer, Ludwig] Childrens Hosp St Elisabeth & St Barbara, Halle, Germany.[Shumikhina, Marina] Filatov Childrens Clin Hosp 13, Moscow, Russia.[Hansen, Matthias] Clementine Childrens Hosp, KfH Ctr Paediat Nephrol, Frankfurt, Germany.[Printza, Nikoleta] Aristotle Univ Thessaloniki, Pediat Dept 1, Thessaloniki, Greece.[Kucuk, Nuran] Kartal Dr Lutfi Kirdar Training & Res Hosp, Istanbul, Turkey.[Beringer, Ortraud] Univ Childrens Hosp, Ulm, Germany.[Bhimma, Rajendra] Cent Hosp, Inkosi Albert Luthuli, Durban, South Africa.[Cerkauskiene, Rimante] Vilnius Univ, Childrens Hosp, Fac Med, Vilnius, Lithuania.[Cerkauskiene, Rimante] Vilnius Univ Hosp, Santaros Klin, Vilnius, Lithuania.[Neuhaus, Thomas J.] Cantonal Hosp Lucerne, Childrens Hosp Lucerne, Luzern, Switzerland.[Stavileci, Valbona] Pediat Clin, Prishtina, Kosovo.[Ulinski, Tim] Armand Trousseau Univ Hosp, APHP, Pediat Nephrol Dept, Paris, France.[Dincel, Nida Temizkan] Hlth Sci Univ, Izmir Dr Behcet Uz Childrens Hosp, Izmir, Turkey.[Mohebbi, Nilufar] Univ Hosp Zurich, Div Nephrol, Zurich, Switzerland