However, conflicting evidence exists that differential expression of a growth factor in gray matter did not translate to detectable differences in expression or levels in the blood or CSF ( Lanz et al., 2012). Previous studies have reported differences in growth factor levels in the CSF ( Kahl et al., 2009 Kiec-Wilk et al., 2010 Takebayashi et al., 2010). We do not know, for example, whether proteins found in the CSF are related to gene expression in the CP or are derived from other brain areas. It is also important to consider the disease relevance of the source material.
The CP has, however, been shown to exhibit alterations following chronic stress in rats, a model known to induce depression-like behavior ( Sathyanesan et al., 2012). Given the proximity of the CP in the lateral ventricle to the hippocampus and the ability of the CP to secrete proteins into the CSF that can act on the hippocampus, it is surprising that this structure has not been previously studied in individuals with mood disorders. This is particularly evident in dissections of the human hippocampus, a brain structure known to respond to antidepressants and play a role in neurogenesis ( Cameron and McKay, 2001 Mallei et al., 2002 Duman, 2004 Bachis et al., 2008). Yet to date, no human post-mortem gene expression studies of the CP have been published.Īs the CP is found largely in the lateral ventricles, it is often co-dissected with surrounding brain tissue. The CP produces cerebrospinal fluid (CSF), removes byproducts, plays a role in neuroendocrine signaling and provides structural support for the brain ( Skipor and Thiery, 2008 Wolburg and Paulus, 2010). The choroid plexus (CP) is composed primarily of capillary beds, the pia mater and a large number of epithelial cells. These results suggest that there may be an altered cytoskeleton in the CP in MDD subjects that may lead to a disrupted blood-CSF-brain barrier. Quantitative real-time PCR (qRT-PCR) confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ) pathway. Using BeadStudio software, we identified 169 transcripts differentially expressed ( p < 0.05) between control and MDD samples. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. In controls, the most highly abundant known transcript was transthyretin.
We then extracted, amplified, labeled, and hybridized the cRNA to Illumina BeadChips to assess gene expression. We performed laser capture microscopy of the CP at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. Genes that are expressed in the CP can be secreted into the CSF and may be potential biomarker candidates. Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus (CP), the region that produces cerebrospinal fluid (CSF), in individuals with major depressive disorder (MDD).
1Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.