The Society for Neuroscience 2019 conference was held on October 19 - 23, 2019 in Chicago, Illinois this year and featured an impressive selection of research from the world’s leading neuroscientists. Insightful poster presentations supported the mainstage presentations on a robust selection of topics. This year three main research topics are highlighted including gene therapy, brain organoids, and neuroinflammation. In addition to the speaker presentations, a large portion of the event was dedicated to manufacturers and service providers demonstrating innovations that support neuroscience research.
Gene Therapy
Gene therapy has the potential to be a groundbreaking treatment option for many neurological diseases such as Parkinson’s and Alzheimer’s. Recent discoveries using postmortem brain data and preclinical animal studies highlight gene therapy's potential for treating these neurological disorders. Gene therapy consists of altering genes to prevent or treat diseases by utilizing inactivated viruses to move genetic information into cells. In the cases of a mutation within a gene, gene therapy can be used to snip and remove the altered gene, and add the functional gene replacement.
“Gene therapy holds the promise to transform the lives of patients with incurable neurological diseases,” said Jeff Kordower, a Rush University Professor and moderator of the Gene Therapy: Curing the Incurable press conference.
Penn State University (PSU) Professor of Biology, Gong Chen, has developed an experimental procedure to investigate gene therapy’s ability to directly reprogram reactive astrocytes into functional motor neurons in mice. His group was able to identify several regulatory genes responsible for the conversion of glial cells into motor neurons in Amyotrophic Lateral Sclerosis (ALS) mouse models. His exciting findings shed light on the enormous potential for gene therapy as a therapeutic approach to restore motor function loss in ALS patients.
Rush researcher, Jeff Kordower, presented on his post-mortem studies regarding neurturin gene therapy in advanced Parkinson’s disease. His study analyzed gene therapy using neurturin, a molecule that enhances dopaminergic neuronal survival and behavioral function in Parkinson’s disease animal models. 2 patients with Parkinson’s disease were given gene therapy to give the neurturin gene in affected regions of the brain. After 8 and 10 years, two follow up postmortem studies were conducted and demonstrated expression of the gene and evidence of the remaining dopamine neuron’s continued functionality. Even though the changes that were observed upon examination were not adequate to provide significant benefits to the two patients, it does indicate the significance of gene therapy for future studies.
Brain Organoids
Lab-grown brain organoids are developing significantly, as their experimental applications are expanding. The brain organoid continues to grow as a strong model system to investigate human brain development and diseases. Brain organoids are self-organizing, 3D tissues that are grown from human stem cells. These stem cells are directed to become structures and cell types found in the brain. A brain organoid has many components of the developing brain, positioning it as an important model of study for human brain development.
“The advances presented today illustrate the exciting potential of using organoids to study brain processes in normal development and disease,” said Hongjun Song, a Professor studying epigenetics and neurogenesis at the University of Pennsylvania Perelman School of Medicine.
Paola Arlotta, a Harvard researcher supporting the efficacy of brain organoids, discussed the reproducibility of brain organoids to create the complex cell diversity of the human cerebral cortex. She analyzed a comparison of 21 organoids derived from distinct cell lines, demonstrating that brain organoids can consistently reproduce the variety of cell types in the human cerebral cortex. These cell classes are indistinguishable when generated from different stem cell lines. She concludes that brain organoids can produce reproducible development of CNS tissue and cell diversity.
Conversely, University of California, San Francisco (UCSF) researcher who casts doubt on the efficacy of brain organoids, Arnold Kriegstein, wishes to establish whether brain organoids have accurate features to generate viable models for epilepsy and autism researchers. This level of modeling will require specific complexities of human cortical development. His analysis of gene expression patterns demonstrated that although the brain organoids provided a variety of cell types, they lacked the cellular complexity found in developing cortex. His research supports the necessity for continued investigation into the efficacy of this exciting modeling system.
Neuroinflammation: Immunity’s Role
The immunity of the brain has opened up exciting advances in research pertaining to neuroinflammation. Degenerative brain diseases, such as Alzheimer’s Disease, are characterized by neuroinflammation. Understanding and researching the causes of neuroinflammation is paramount to uncovering treatment options for the future. Immune cells located in the brain, microglia, have given researchers important insights into the human body’s inflammatory response. The changes seen in microglia in response to inflammation is characteristic of several neurodegenerative diseases including depression and autism.
Donna Wilcock, a Professor at the University of Kentucky, is researching vascular cognitive impairment and dementia. At SfN she stated, “We are only beginning to understand the complex interplay between the immune system and the brain, and we don’t yet know how to manipulate it effectively. This research will further our understanding of these challenges and find a way forward to treat patients with inflammation due to disease or injury.”
Rush researcher, Kalilpada Pahan, analyzed how aspirin upregulates IL-1Ra in glial cells via PPAR-Alpha. His research team utilized mouse models to demonstrate small doses of aspirin can upregulate IL-1Ra, a molecule that inhibits neuroinflammation. After mice were fed aspirin, they demonstrated increased cognitive function.
Neuroscience Technology Spotlight
Brain Mapping Software
Inscopix, Inc. (Palo Alto, CA) developed new software features that enable researchers to map neuronal activity in multiple planes simultaneously. This will increase the number of cells that can be imaged in the brain. Additional software innovations include data compression which helps researchers decrease their time of transfer and increase the scale of their projects.
In efforts to optimize laboratory workflows, Inscopix is launching an expanded portfolio of its Proview™ Express Probes and Proview™ Integrated Lenses.
New Workflows for Neural Network Research
Carl Zeiss AG (Oberkochen, Germany) and Inscopix have collaborated to produce new workflows for neural network research. Using the ZEISS Airyscan confocal imaging technology with Inscopix’s freely behaving microscopy system, the collaboration will generate fantastic image resolution and live imaging with multi-channel capabilities. The fusion of these technologies will optimize in vivo imaging in mice models and allow researchers a means to monitor neural signaling during social interactions, addiction, sleep, and spatial memory with significant imaging capabilities.
Confocal Microscopy
The Airyscan 2 confocal microscope was launched earlier this year by Carl Zeiss AG and contains several impressive features. Airyscan 2 is an area detector with 32 concentrically arranged detection elements. These modifications will yield increased resolution, decreased noise and better signal. Additionally, the Airyscan 2 contains a 2,4,8 pixel scanning per sweep capability.
Structural Illumination Microscopy
The Zeiss Elyra 7 with lattice SIM (structural illumination microscopy) offers several advantages including gentler imaging, faster imaging (255 phases per second), and 2x magnification improvement. This system does not overlap and uses a grid scan which will prevent roasting of the user’s sample.
3D Neuronal Imaging
The UltraMicroscope II light sheet microscope from Miltenyi Biotech (Bergisch Gladbach, Germany) combined with the MACSima™ imaging platform and the TriM Scope II modular 2-photon microscope platform from LaVision BioTec GmbH (Bielefeld, Germany) provides fast 3D imaging of the Ultramicroscope II with the high content imaging and live animal imaging of the MACSima™ Imaging Platform and TriM Scope II.
The MuVi SPIM multiview light-sheet microscope from Bruker (Middleton, WI) generates 3D imaging of large life specimens and cleared tissue. Its unique 4-axis concept and vibration-free design is capable of a resolution down to 280 nm in 3D.
Live Cell Imaging & Analysis
The IncuCyte S3® live cell analysis system from Essen BioScience, a Sartorius company (Ann Arbor, MI) performs automated, real-time measurements of living neural cells from the incubator directly. The automated image capture and analysis of neuronal cell activity can be performed in 96 and 384 well options. The powerful image and movie capabilities of the IncuCyte S3® live cell analysis system is optimally designed to view changes and validate measurements over weeks to month-long studies on cells as they are incubated.
The Zeiss Celldiscover 7 high-end imaging system from Carl Zeiss AG enables automated 4D live cell imaging. It has leading magnification capabilities and has detection capabilities that utilize a machine learning-based algorithm. In addition to its impressive hypoxic condition capabilities, the Zeiss Celldiscover 7 allows the user to put in the point-scanning LSM-900 and/or the Airyscan within the Zeiss suite of microscopy solutions for increased capability.