Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory

The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer's disease

Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail.</p> <p>Results</p> <p>THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells.</p> <p>Conclusion</p> <p>CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.</p

Influence of Rapamycin to Myelin Abnormalities in a Mouse-Model of a Tomaculous Neuropathie

Tomakula und andere Formen von fokal gefaltetem Myelin sind auffällige neuropathologische Zeichen einiger demyelinisierender Neuropathien, einschließlich der Charcot-Marie-Tooth (CMT) -4B, CMT4F, CMT1B und der hereditären Neuropathie mit Neigung zu Druckparesen (HNPP). Im Gegensatz zum weiten Fortschritt bei den Untersuchungen der genetischen Grundlagen dieser Erkrankungen sind die molekularen Mechanismen, die dieses fokale Myelinwachstum begründen und die Interaktionen zwischen Schwannzellen und Axonen in einigen Formen der CMT stören, aber nicht in anderen, weiterhin unklar. Vermutlich resultieren Myelinausfaltungen und Tomakula aus einem unkontrollierten, stark angestiegenen Myelinmembranwachstum, ein Prozess, der zumindest teilweise abhängig ist vom Neuregulin-1/ErbB2 und -PI3K-Signalweg. Voruntersuchungen an Mäusen mit fehlender PTEN-Expression in Schwannzellen zeigten, dass eine Gliazell-spezifische Hyperaktivierung des endogenen PI3K-Signalweges fokale Hypermyelinisierungen, Myelinausfaltungen und Tomakula verursacht. Weiterhin fand sich eine Aktivierung der AKT-Kinase, welche mit Phosphatidylinositol-3,4,5-trisphosphat (PtdIns(3,4,5)P3, PIP3) assoziiert ist, an den Paranodien und an den Schmidt-Lanterman-Inzisuren. Dies und die fokalen Hypermyelinisierungen geben einen Hinweis darauf, dass in Regionen unkompakten Myelins Membranfaltungen und Myelinwachstum stattfinden, welche bedeutend durch PTEN kontrolliert werden. In dieser Arbeit ist der Einfluss des spezifischen mTOR-Inhibitors Rapamycin auf die pathologischen Myelinmissbildungen in konditionellen PTEN-Maus-Mutanten untersucht worden. Interessanterweise zeigen die Ergebnisse, dass die Ausbildung der Tomakula und der Myelinausfaltungen stark vom AKT/mTOR-Signalweg abhängig sind, was durch eine signifikante Verhinderung der Pathologien nach Rapamycingabe bewiesen werden konnte. In diesem Mausmodel führten verstärkte Level von PIP3 zur Entwicklung von Pathologien tomakulöser Neuropathien. Ob jedoch Rapamycin auch einen positiven Einfluss auf Mausmodelle humaner tomakulöser Neuropathien, wie die der HNPP, ausüben kann, ist noch unklar und muss weitergehend untersucht werden

To share or not to share : clonal integration in a submerged macrophyte in response to light stress

The ability of clonal plant species to share resources has been studied in many experiments. The submerged macrophyte Potamogeton perfoliatus produces interconnected ramets within short time intervals and hence may or may not share resources with ramets growing in less favourable microhabitats. From a genet point of view, sharing with ramets growing under less favourable conditions might not be an optimal strategy when photosynthates could be used to establish other ramets growing under more favourable conditions. To analyse the plasticity in clonal integration of P. perfoliatus, we set up a factorial aquaria experiment with unshaded or shaded recipient ramets (offspring), which were connected to or separated from donor ramets (parents). Increased biomass production of offspring in parent–offspring systems compared with severed offspring in both light and shade showed that ramets share resources through clonal integration. The relative translocation to the first- and second-offspring generation was influenced by habitat quality: If first-offspring ramets grew in a shaded microhabitat, second-offspring ramets clearly profited. This may be at least partially because of the fact that resources are shifted from first-offspring to second-offspring ramets, indicating controlled senescence of the first-offspring. This complex sharing behaviour might be relevant when plants produce ramets within a dense patch of macrophytes, where support of a shaded ramet might not pay off

Density control in Potamogeton perfoliatus L. and Potamogeton pectinatus L.

The effect of density on the growth, recruitment of new ramets, biomass allocation, rhizome spacer length and rhizome branching of the submersed macrophyte Potamogeton perfoliatus L. was experimentally evaluated in a mesocosm with three different initial shoot densities. The findings suggest that the number of primary shoots available in the beginning of the season can strongly influence patterns of growth and clonal reproduction. In contrast to many studies that found decreasing production parameters with plant density, ramet and biomass production of Potamogeton perfoliatus plants were highest at medium plant density. This is probably due to negative feed-back through crowding at high density and unclear negative effects at low density. Shoot allocation tended to increase with density, rhizome allocation tended to decrease with density and root biomass remained unchanged. At low density Potamogeton perfoliatus produced longer rhizome spacers and more branchings than at higher densities. Shorter rhizome spacers at high plant density probably restrict patch expansion and cause discrete patch shapes. A likely mechanism for plastic changes in clonal architecture is increasing competition for light at increasing density, but other density-dependent factors mayaiso contribute. Investigations on propagule numbers of tubers and turions show that self-regulation of ramet number was associated with self-regulation of propagule number in both Potamogeton perfoliatus and Potamogeton pectinatus, with higher densities producing less propagules per plant

Spatio-temporal dynamics and plasticity of clonal architecture in Potamogeton perfoliatus

Above- and below-ground clonal growth architecturewas compared for two neighbouring patches of Potamogeton perfoliatus L. in Lake Constance, representing typical sparse and dense growth types. A detailed map of individual ramets and their corresponding rhizome network was produced and the seasonal development of ramet sprouting and rhizome growth was reconstructed. Rhizomesextended at rates ranging between 40 and 63 cm per year, and added a newshoot for every 1 20 cm of rhizome produced. The main rhizome axis grewin a semi-linear fashion, with deviation means of 15 and 24 degr., and developed 0 0.5 branches per plant, with an insertion angle from 15 90 degr.. Total rhizomelength of all plants amounted to 5 and 11mm−2 at the two sites. The total biomass produced at the two sites differed by 10-fold. The neighboring patches also showed different allocation patterns which are interpreted as foraging.Contrary to the prediction of the foraging hypothesis, there was only a small difference in mean spacer length between sites. On the other hand, the spacer length was plastic relatively to total biomass. We propose that spacer length is not an independent part of the foraging strategy, but rather a result of overall productivity and biomass allocation. Phosphorus content of plant tissue atthe more productive site was two-fold higher than that at the less productive site which suggests that the different growth types may be due to differences in sediment nutrient availability: in situ fertilization of a less productive site increased the P content to those levels of the productive site. In situ fertilization also resulted in higher ramification, lower root allocation and decreased spacer length and confirmed the foraging capability of P. perfoliatus

Modelling the clonal growth of the rhizomatous macrophyte Potamogeton perfoliatus

Macrophytes play a crucial role in the functioning of lake ecosystems. Until now most macrophyte models neglected the fact that the majority of macrophyte species expand clonally during the growing season. Inclusion of a detailed description of clonal growth in models can facilitate our understanding of space occupation and patch expansion and predict future macrophytedevelopment. CLOMO is an individual-based model which includes a detailed, spatially explicit description of rhizome formation and clone expansion as well as a realistic description of photosynthesis including light limitation and temperature.The model also accounts for transfers of energy or resources between different parts of the clone ( clonal integration ). Although the clonal growth of macrophytes is complex and poorly known, the first model results for the macrophyte species Potamogeton perfoliatus were promising and compared well with the field data. The model can produce growth networks very similar to those found in the field. A Monte Carlo sensitivity analysis showed systematically which parameters have the largest effect on the architecture and expansion of the clones. The application of the model provided new insights into growth dynamics and patch development: (1) the model showed that a lack of branching will lead to the extinction of the clone after a certain number of years. This is due to the fact that the reproductive organs (turions) are formed at the end of a branch and even a small turion mortality will cause a reduction in surviving plant numbers; (2) the growth of rhizome axes relative to those in the previous year determines the patch density and patch expansion rate. Reversing rhizomes lead to compact patch growth whereas continuing rhizomes lead to loose aggregates

Semi-quantitative assessment of environmental tobacco smoke exposure and its association with the development of oral squamous cell carcinoma: A pilot study

Two known major risk factors for oral squamous cell carcinoma are smoking and alcohol consumption. Environmental tobacco smoke (also known as secondhand smoke) has been proven to be associated with the occurrence of lung and breast carcinoma. This study aimed to assess exposure to environmental tobacco smoke and its association with the development of oral squamous cell carcinomas.Open-Access-Publikationsfonds 202

Knowledge and skills of emergency physicians in managing traumatic dental injuries

Purpose!#!Emergency departments are frequently confronted with traumatic dental injuries (TDIs). The prognosis of the injured tooth is related to early dental trauma management. For this reason, physicians must be familiar with the appropriate management of TDI. This study aimed to investigate the knowledge and skills of German emergency physicians regarding TDI.!##!Methods!#!An electronic questionnaire was sent to 438 emergency departments throughout Germany. Four hundred and twenty seven questionnaires were evaluated and included in the analysis. The survey contained questions about physician characteristics and assessed their knowledge and skills of managing dental trauma. For statistical analysis, the Kruskal-Wallis, Mann-Whitney U test or ANOVA test was used as appropriate. Rank correlations were performed with the Spearman's rank correlation.!##!Results!#!Out of 427 participants, 256 (59.95%) stated they had no or insufficient knowledge, and 266 (71.12%) stated they had no skills in dental trauma management. Almost 76% of the participants had no previous knowledge of dentistry. Only 7.28% knew the right procedure for replanting an avulsed tooth. Just 26.06% would choose the right medium for temporary tooth storage. Having a dentist in the family (p = 0.0074) or clinical exposure to patients with dental trauma (p = 0.0384) influenced the results of the knowledge score.!##!Conclusion!#!The knowledge and skills in dental trauma management among German emergency physicians are generally inadequate. Targeted training courses are necessary to ensure early and adequate TDI treatment to reduce the resulting medical and societal costs as much as possible