Calcyon transcript expression in macaque brain

The anatomical distribution of the transcript encoding calcyon, a 24 kDa membrane protein associated with coupling D1-like dopamine receptor activation to potentiated intracellular calcium release, was examined using in situ hybridization in the macaque brain. Calcyon mRNA is found to be abundantly distributed throughout the primate brain. In neocortex, moderately dense, diffuse signal is found in all areas, with increased intensity present in a superficial isodense band corresponding generally to cortical layers II and III. Increased intensity of signal is also seen in the pyramidal cell layers of medial prefrontal and anterior cingulate cortex. Calcyon mRNA is present abundantly in subcortical limbic areas such as the nucleus accumbens, septum, hypothalamus, amygdala, and hippocampus. Moderate calcyon transcript expression is seen in caudate and putamen, with lower levels in globus pallidus. Thalamic nuclei, including the reticular nucleus, express low to moderate levels. Very dense expression is noted in the substantia nigra pars compacta. Numerous brainstem regions express this transcript, notably monoaminergic nuclei including the locus coeruleus and dorsal raphe. The cerebellum has detectable levels of expression in both cortex and deep nuclei. Although calcyon is hypothesized as a means for D1-like receptors to modulate “cross-talk” with other neurotransmitter receptor systems, it is notable that abundant calcyon transcript is detected in brain regions not associated with D1-like neurotransmission, particularly the substantia nigra pars compacta and other dopamine-synthesizing cell groups. A substantial proportion of this may relate to the reported association of calcyon with the D5 receptor, or in addition, may suggest that calcyon has a wider role as a regulator of intracellular signal transduction. J. Comp. Neurol. 468:264–276, 2004. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34469/1/10993_ftp.pd

Basal ganglia mineralization in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29488/1/0000574.pd

Expression of transcripts encoding AMPA receptor subunits and associated postsynaptic proteins in the macaque brain

Glutamate is the primary excitatory neurotransmitter in the central nervous system, regulating numerous cellular signaling pathways and controlling the excitability of central synapses both pre- and postsynaptically. Localization, cell surface expression, and activity-dependent regulation of glutamate receptors in both neurons and glia are performed and maintained by a complex network of protein–protein interactions associated with targeting, anchoring, and spatially organizing synaptic proteins at the cell membrane. Using in situ hybridization, we examined the expression of transcripts encoding the AMPA receptor subunits (GluR1–GluR4) and a family of AMPA-related intracellular proteins. We focused on PDZ-proteins that are involved in the regulated pool and anchoring AMPA subunits to the cell membrane (PICK1, syntenin), and those maintaining the constitutive pool of AMPA receptors at the glutamatergic synapse (NSF, stargazin). In addition, we studied a fifth protein, KIAA1719, with high homology to the rat PDZ protein ABP, associated with the clustering of AMPA receptors at the glutamate synapse. The AMPA subunits showed significant differences in regional expression, especially in the neocortex, thalamus, striatum, and cerebellum. The expression of other proteins, even those related to a specific AMPA subunit (such as ABP and PICK1 to GluR2 and GluR3), often had different distributions, whereas others (like NSF) are ubiquitously distributed in the brain. These results suggest that AMPA subunits and related intracellular proteins are differentially distributed in the macaque brain, and in numerous structures there are significant mismatches, suggesting additional functional properties of the associated intracellular proteins. J. Comp. Neurol. 468:530–554, 2004. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34470/1/10981_ftp.pd

Expression of the dopamine D2 receptor gene in brain,

The cloning of the dopamine (DA) D2 receptor now permits the characterization and regulation of D2 messenger RNA (mRNA) in the brain. In this article, the authors describe their studies delineating the distribution of D2 receptor mRNA in the rodent and primate brain, and compare the distribution of message to D2 receptor binding sites. The effects of chronic DA agonist and antagonist treatment on D2 receptor mRNA are also presented, and provide insights into receptor regulation. Finally, the autoreceptor role of D2 receptors located in the midbrain is examined with a combination of 6-hydroxydopamine lesions and anatomic colocalization studies with tyrosine hydroxylase. These preclinical results provide a framework for subsequent investigation into the nature of D2 receptor gene expression in postmortem brains from patients with disorders putatively associated with dopaminergic dysfunction, especially schizophrenia. They also lay the groundwork for a more profound understanding of DA neurocircuitry by combining molecular biological and traditional anatomical techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29030/1/0000062.pd

Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long-term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness. Synapse 57:123–131, 2005. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48692/1/20164_ftp.pd

Ampa Receptor Subunit Expression in the Endoplasmic Reticulum in Frontal Cortex of Elderly Patients with Schizophrenia

Several lines of evidence indicate altered trafficking of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors in schizophrenia. Previous reports have shown potential changes in the trafficking of AMPA receptors based on subunit expression of endosomes, subcellular organelles located near post-synaptic sites. We hypothesized that alterations in AMPA receptor trafficking through the endoplasmic reticulum (ER) may also be altered in schizophrenia. Accordingly, we developed a technique to isolate and measure content of the ER from postmortem brain tissue. We used Western blot and electron microscopy to show that we isolated an ER enriched fraction. We found no changes in the expression of the AMPA receptor subunits, GluR1–4, in the ER from the dorsolateral prefrontal cortex in schizophrenia. These data suggest that AMPA receptor trafficking through the ER is largely intact in schizophrenia

Prodynorphin-derived peptide expression in primate cortex and striatum

The distributions of four prodynorphin-derived peptides, dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and [alpha]-neo-endorphin were determined in 10 cortical regions and the striatum of the old world monkey (Macaca nemestrina). [alpha]-neo-endorphin was the most abundant peptide in both cortex and striatum. The concentrations of all four peptides were significantly greater in the striatum compared to the cortex. In general, concentrations of each peptide tended to be higher in allocortex than in neocortex. Possible inter- and intradomain processing differences, as estimated by ratios of these peptides, did not vary within cortex, but the intradomain peptide ratio, dyn A (1-17)/dyn A (1-8), was significantly greater in cortex than in striatum. These results indicate that prodynorphin is, in some ways, uniquely processed in the primate. Particularly unusual is the relatively low abundance of prodynorphin-derived products in the cortex, in the face of moderately high levels of kappa opiate receptor expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31211/1/0000113.pd

Expression of prodynorphin-derived peptides and mRNA in guinea-pig cortex

The distributions and extent of processing of four prodynorphin-derived peptides (dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and [alpha]-neoendorphin) were determined in ten regions of the cortex as well as in the striatum of the guinea-pig. There were significant differences between concentrations of these peptides in most cortical regions, with [alpha]-neoendorphin being several times more abundant than the other peptides, and dynorphin A (1-17) being present in the least amount. There were significant between-region differences in concentration for each peptide, although most regions had concentrations similar to those seen in the striatum. Concentrations of each peptide tended to be higher in piriform, entorhinal, motor, and auditory cortex than in other cortical regions. The extent of processing of prodynorphin varied across cortical regions as well, primarily due to the extent of processing to [alpha]-neoendorphin. Prodynorphin mRNA levels were not significantly different between cortical regions or from the amount observed in the striatum. Although specific regional variation exists, it appears that in general prodynorphin is expressed and processed in a similar manner in the cortex as in the striatum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30648/1/0000290.pd

Severity of depression and hypothalamic-pituitary-adrenal axis dysregulation: identification of contributing factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65507/1/j.1600-0447.1990.tb05465.x.pd

Dopamine receptor messenger RNA: Localization in the human hippocampus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30871/1/0000535.pd