Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells.

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease.

Biofunctionalised bacterial cellulose scaffold supports the patterning and expansion of human embryonic stem cell-derived dopaminergic progenitor cells.

Background: Stem cell-based therapies for neurodegenerative diseases like Parkinson's disease are a promising approach in regenerative medicine and are now moving towards early stage clinical trials. However, a number of challenges remain including the ability to grow stem cells in vitro on a 3-dimensional scaffold, as well as their loss, by leakage or cell death, post-implantation. These issues could, however, be helped through the use of scaffolds that support the growth and differentiation of stem cells both in vitro and in vivo.

Calcium imaging analysis - how far have we come?

Techniques for calcium imaging were first demonstrated in the mid-1970s, whilst tools to analyse these markers of cellular activity are still being developed and improved today. For image analysis, custom tools were developed within labs and until relatively recently, software packages were not widely available between researchers. We will discuss some of the most popular methods for calcium imaging analysis that are now widely available and describe why these protocols are so effective.

Synaptic tau: A pathological or physiological phenomenon?

In this review, we discuss the synaptic aspects of Tau pathology occurring during Alzheimer's disease (AD) and how this may relate to memory impairment, a major hallmark of AD. Whilst the clinical diagnosis of AD patients is a loss of working memory and long-term declarative memory, the histological diagnosis is the presence of neurofibrillary tangles of hyperphosphorylated Tau and Amyloid-beta plaques. Tau pathology spreads through synaptically connected neurons to impair synaptic function preceding the formation of neurofibrillary tangles, synaptic loss, axonal retraction and cell death.

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy.

Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy.

OptiJ: Open-source optical projection tomography of large organ samples.

The three-dimensional imaging of mesoscopic samples with Optical Projection Tomography (OPT) has become a powerful tool for biomedical phenotyping studies. OPT uses visible light to visualize the 3D morphology of large transparent samples. To enable a wider application of OPT, we present OptiJ, a low-cost, fully open-source OPT system capable of imaging large transparent specimens up to 13 mm tall and 8 mm deep with 50 µm resolution.

Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory.

Disrupting maladaptive memories may provide a novel form of treatment for neuropsychiatric disorders, but little is known about the neurochemical mechanisms underlying the induction of lability, or destabilization, of a retrieved consolidated memory. Destabilization has been theoretically linked to the violation of expectations during memory retrieval, which, in turn, has been suggested to correlate with prediction error (PE). It is well-established that PE correlates with dopaminergic signaling in limbic forebrain structures that are critical for emotional learning.

Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology.

Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The aggregates are an early and progressive pathology that occur at 3 months of age and increase in both size and number over time.