Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex

Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT) or glutamic acid decarboxylase (GAD) mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85%) between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type-specific manner to better understand its role in stress-related psychiatric disorders, including anxiety, depression and addiction

hVH-5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen-Activated Protein Kinase

A novel protein tyrosine phosphatase [ h omologue of v accinia virus H 1 phosphatase gene clone 5 (hVH-5)] was cloned; it shared sequence similarity with a subset of protein tyrosine phosphatases that regulate mitogen-activated protein kinase. The catalytic region of hVH-5 was expressed as a fusion protein and was shown to hydrolyze p -nitrophenylphosphate and inactivate mitogen-activated protein kinase, thus proving that hVH-5 possessed phosphatase activity. A unique proline-rich region distinguished hVH-5 from other closely related protein tyrosine phosphatases. Another feature that distinguished hVH-5 from related phosphatases was that hVH-5 was expressed predominantly in the adult brain, heart, and skeletal muscle. In addition, in situ hybridization histochemistry of mouse embryo revealed high levels of expression and a wide distribution in the central and peripheral nervous system. Some specific areas of abundant hVH-5 expression included the olfactory bulb, retina, layers of the cerebral cortex, and cranial and spinal ganglia. hVH-5 was induced in PC12 cells upon nerve growth factor and insulin treatment in a manner characteristic of an immediate-early gene, suggesting a possible role in the signal transduction cascade.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65883/1/j.1471-4159.1995.65041823.x.pd

Localization of the corticotropin-releasing hormone receptor gene on mouse Chromosome 11

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47014/1/335_2004_Article_BF00350896.pd

Corticotropin-releasing hormone ( Crh ) maps to mouse Chromosome 3

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46997/1/335_2004_Article_BF00361396.pd

Decreased locomotor activity in mice expressing tTA under control of the CaMKIIΑ promoter

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72144/1/j.1601-183X.2007.00339.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72144/2/GBB339Figs_S1-3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72144/3/GBB_339_sm_FigureS1-3.pd

Novel Roles for CRF‐Binding Protein and CRF Receptor 2 in Binge Drinking

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134133/1/acer12897.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134133/2/acer12897_am.pd

Binge Drinking Decreases Corticotropin‐Releasing Factor‐Binding Protein Expression in the Medial Prefrontal Cortex of Mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133535/1/acer13119.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133535/2/acer13119_am.pd