Cholinergic and inflammatory phenotypes in transgenic tau mouse models of Alzheimer’s Disease and Frontotemporal Lobar Degeneration

All authors have made a substantial, direct and intellectual contribution to the work, and approved it for publication. This work was funded by NCN grant 2014/15/B/NZ4/05041 and WisTa Laboratories Ltd. CH and CW serve as officers in both WisTa Laboratories Ltd. and TauRx Therapeutics Ltd. The sponsor was involved in the design of the study; in the collection, analysis and interpretation of data; and in the writing of the report. The corresponding authors had full access to all the data and had final responsibility for submission of the report for publication.Peer reviewedPublisher PD

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient’s brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD

The patterns and puzzles of genetic diversity of endangered freshwater MusselUnio crassusPhilipsson, 1788 populations from Vistula and Neman drainages (Eastern Central Europe)

Mussels of the family Unionidae are important components of freshwater ecosystems. Alarmingly, the International Union for Conservation of Nature and Natural Resources Red List of Threatened Species identifies almost 200 unionid species as extinct, endangered, or threatened. Their decline is the result of human impact on freshwater habitats, and the decrease of host fish populations. The Thick Shelled River MusselUnio crassusPhilipsson, 1788 is one of the examples that has been reported to show a dramatic decline of populations. Hierarchical organization of riverine systems is supposed to reflect the genetic structure of populations inhabiting them. The main goal of this study was an assessment of theU. crassusgenetic diversity in river ecosystems using hierarchical analysis. Different molecular markers, the nuclear ribosomal internal transcribed spacer ITS region, and mitochondrial DNA genes (cox1andndh1), were used to examine the distribution ofU. crassusamong-population genetic variation at multiple spatial scales (within rivers, among rivers within drainages, and between drainages of the Neman and Vistula rivers). We found high genetic structure between both drainages suggesting that in the case of the analyzedU. crassuspopulations we were dealing with at least two different genetic units. Only about 4% of the mtDNA variation was due to differences among populations within drainages. However, comparison of population differentiation within drainages for mtDNA also showed some genetic structure among populations within the Vistula drainage. Only one haplotype was shared among all Polish populations whereas the remainder were unique for each population despite the hydrological connection. Interestingly, some haplotypes were present in both drainages. In the case ofU. crassuspopulations under study, the Mantel test revealed a relatively strong relationship between genetic and geographical distances. However, in detail, the pattern of genetic diversity seems to be much more complicated. Therefore, we suggest that the observed pattern ofU. crassusgenetic diversity distribution is shaped by both historical and current factors i.e. different routes of post glacial colonization and history of drainage systems, historical gene flow, and more recent habitat fragmentation due to anthropogenic factors