There is a high demand for in vitro models of the central nervous system (CNS) to study neurological disorders, injuries, toxicity, and drug efficacy. The behavior of 3D-cultured cells is a more accurate model of in vivo cellular responses, especially in the brain, when compared to 2D-cultures. These models can replicate cell–cell interactions and physiological functions, giving them the potential to decrease drug failure, improve treatments, and predict toxicity response by furthering our understanding of these complex systems.

For example, our lab works with domoic acid, a harmful neurotoxin that targets the CNS. Exposure to domoic acid, which can be found in shellfish and other seafood, has been linked to Autism Spectrum Disorder. Other toxicants we are testing include, nicotine, caffeine, and vincristine. In addition to our existing rodent neural microtissue model, our goal is to develop reliable human neural microtissues that we can leverage to aid in the investigation of human response to a variety of toxins.

Rodent cortical microtissues stained for glial fibrillary acidic protein (green), beta tubulin III (red), and DAPI (cyan), exhibit reactive astrocytes and disrupted neurite networks following either no exposure (left) or 10 uM exposure (right) to domoic acid.

Human cortical microtissue stained for GFAP (astrocytes), beta tubulin III (neurites), and DAPI (cell bodies).

Rodent cortical microtissue stained with Hoesct (cyan) and synapsin (red) demonstrate decreased synaptic density following either no exposure (right) or 10 uM exposure (left) to domoic acid.