Decreased neural connectivity in cultured schizophrenia patient neurons

Brennand et al took an interesting approach to this question in their recent article. They took some non-neuronal cells from four patients with schizophrenia (and six controls), reprogrammed them into stem cells, induced them to become neural progenitor cells (mostly glutamatergic), and, finally, cultured them in vitro.

The researchers then used trans-synaptic viral tracing to visualize the connections between cultured neurons in the schizophrenia patients and healthy controls with fluorescent proteins.

To me their major finding was that the cultured cells of patients with schizophrenia had fewer connections. That is, the ratio of cells initially infected with the virus to cells secondarily infected through a synaptic connection was lower in the schizophrenia patients. Eyeing fig 2b, it looks like this ratio is ~ 1.2 +/- 0.1 in the cells from healthy patients, while it is ~ 0.55 +/- 0.05 in the cells from patients with schizophrenia. They show some beautiful representative images of this, which I at first thought must be false colored. But no, they’re real. Wow.

The degree to which schizophrenia manifests as a “connectopathy” is a highly contentious issue, but this study adds to the suggestion that neural connectivity does play at least some sort of a role in the etiology of the disease.

(Also blogged at Neuroskeptic.)

Reference

Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, & Gage FH (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature. doi:10.1038/nature09915 PMID: 21490598