How Neuroscientists Can Use Live-Cell Analysis

Recent decades have observed extraordinary developments in the field of neuroscience. Deep sequencing and epidemiological research, for instance, has presented excellent insight into the genetic basis for neurological disease.

High-resolution methods have also resolved many signaling pathways for learning and memory at both the cellular and molecular level. Although this is the case, discovering new, truly efficient therapies for patients has been difficult, and the majority of human brain and nervous system functions continue to be an enigma.

A number of fundamental difficulties exist. First of all, the nervous system is tremendously complex, with more than 100 billion interconnected neurons contained in the average human brain, and plenty more support cells. These cells are highly plastic and are continually changing during development, adult life and the virtually inevitable decline of age and disease.

Secondly, it is extremely hard to access living healthy and diseased human neural tissue for studies with ethical consent. Small biopsy samples may be attained, but are seldom adequate for in-depth in vitro analyses and functional research. When comparing all cells, neurons are enormously sensitive to damage or environmental change, such as hypoxia, which augments additional technical complexity.

Lastly, in a large proportion of cases, animal models have generated uncertain translational value, especially for psychiatric and neurodegenerative illnesses, used only to emphasize the prominent differences between lower and higher order species.

Recent developments in stem cell technologies provide a stimulating alternative pathway where investigators can utilize human induced pluripotent stem cells (iPSCs) to generate differentiated neurons and support cells, for example, astrocytes or microglia.

While this method is in its initial stages, there is potential to create fully humanized, patient-specific advanced cell models for neuroscience. To achieve this promise, significant research is needed to optimize the reprogramming and differentiation approaches, and to create and validate cellular bioassays that are representative of native human (patho) physiology. Phenotypic measurements that provide functional results and long-term plastic changes will be extremely helpful in this regard.

With this in mind, this white paper discusses live-cell analysis methods and describes a collection of neurobiology applications that are amenable for research in human iPSCs in addition to primary cell models.

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Last updated: Jul 16, 2020 at 4:42 AM

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