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Mental Illness and Cellular Interactions

Much research in neurology and psychiatry focuses on neurotransmitters and receptors that transfer information between brain cells (neurons) at specialized sites called synapses. But just like all the other cells in your body, neurons depend on many other cellular interactions in order to function properly. These interactions contribute to brain development during childhood and to neuron function in the adult, and thereby may affect mental illness occurence and recovery.

One broad type of cellular interaction is referred to as “Wnt signaling.” Wnt signaling is crucial in all multicellular animals, and when disrupted can lead to diseases in humans.

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Wnt signaling, neuropsychiatry, and developmental biology websites.

Wnt signaling is present in the developing and mature brain. Among other effects, it helps to determine the structure and size of brain regions, and to regulate when and how neurons mature. Protein components of the Wnt signaling pathway help regulate neuron location, shape, and connections at synapses. Altering these proteins in experimental animals affects social and cognitive behavior. Corresponding genes in humans have been linked to mental illnesses at all stages of life including autism, schizophrenia, bipolar disorder, depression, and dementia.

We are investigating intracellular proteins that help regulate this and related signaling pathways inside cells, including in neurons. We seek to understand how these proteins operate both in the developing embryo and in the brain. Our embryonic studies are especially relevant to birth defects, whereas our brain studies are relevant to the biology of mental illness. In practice, we have found that these technical approaches are highly complementary: our discoveries in the embryo inform further investigations in the brain, and vice-versa.

The tools we use are recombinant DNA technology, mammalian tissue culture, and gene-targeted and transgenic strains of laboratory mice.