Sharon Burke
University of Michigan
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Featured researches published by Sharon Burke.
Hormones and Behavior | 2000
Xin Yun Lu; Didier Bagnol; Sharon Burke; Huda Akil; Stanley J. Watson
To further understand the functions of the orexin/hypocretin system, we examined the expression and regulation of the orexin/hypocretin receptor (OX1R and OX2R) mRNA in the brain by using quantitative in situ hybridization. Expression of OX1R and OX2R mRNA exhibited distinct distribution patterns. Within the hypothalamus, expression for the OX1R mRNA was largely restricted in the ventromedial (VMH) and dorsomedial hypothalamic nuclei, while high levels of OX2R mRNA were contained in the paraventricular nucleus, VMH, and arcuate nucleus as well as in mammilary nuclei. In the amygdala, OX1R mRNA was expressed throughout the amygdaloid complex with robust labeling in the medial nucleus, while OX2R mRNA was only present in the posterior cortical nucleus of amygdala. High levels of OX2R mRNA were also observed in the ventral tegmental area. Moreover, both OX1R and OX2R mRNA were observed in the hippocampus, some thalamic nuclei, and subthalamic nuclei. Furthermore, we analyzed the effect of fasting on levels of OX1R and OX2R mRNA in the hypothalamic and amygdaloid subregions. After 20 h of fasting, levels of OX1R mRNA were significantly increased in the VMH and the medial division of amygdala. An initial decrease (14 h) and a subsequent increase (20 h) in OX1R mRNA levels after fasting were observed in the dorsomedial hypothalamic nucleus and lateral division of amygdala. Levels of OX2R mRNA were augmented in the arcuate nucleus, but remained unchanged in the dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus, and amygdala following fasting. The time-dependent and region-specific regulatory patterns of OX1R and OX2R suggest that they may participate in distinct neural circuits under the condition of food deprivation.
Biological Psychiatry | 2004
Antonio L López-Figueroa; Camille S. Norton; Manuel O. López-Figueroa; Denise Armellini-Dodel; Sharon Burke; Huda Akil; Juan F. Lopez; Stanley J. Watson
BACKGROUND Alterations of serotonin neurotransmission are implicated in both mood disorders and schizophrenia. Specific serotonin-receptor-based abnormalities in these psychiatric illnesses have been intensively studied; however, it has been difficult to draw any conclusions because of a lack of consensus. These inconsistencies have most likely arisen from the unavailability of selective ligands. METHODS Our study used in situ hybridization to quantify 5-HT(1A), 5-HT(1B), and 5-HT(2A) mRNA levels in the hippocampus (HC) and 5-HT(1A) and 5-HT(2A) mRNA levels in the dorsolateral prefrontal cortex (DLPFC) of subjects with a history of major depression disorder (MDD), bipolar disorder (BPD), schizophrenia, and a normal comparison group (15 subjects per group). RESULTS In the DLPFC, there is a significant decrease in 5-HT(1A) mRNA of subjects with MDD and in 5-HT(2A) mRNA of subjects with BPD. Subjects with MDD have a significant decrease in 5-HT(1A) mRNA in the HC; subjects with BPD and schizophrenia had increased 5-HT(1B) mRNA levels and a significant decrease in 5-HT(2A) mRNA levels in the hippocampal formation. CONCLUSIONS Alterations in 5-HT(1A,) 5-HT(1B), and 5-HT(2A) mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders.
The Journal of Neuroscience | 2004
Kenneth J. Rhodes; Karen I. Carroll; M. Amy Sung; Lisa C. Doliveira; Michael M. Monaghan; Sharon Burke; Brian W. Strassle; Lynn Buchwalder; Milena Menegola; Jie Cao; W. Frank An; James S. Trimmer
Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family α subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family α subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 α subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.
Journal of Psychiatric Research | 2000
Paresh D. Patel; Juan F. Lopez; David M. Lyons; Sharon Burke; Melissa Wallace; Alan F. Schatzberg
Corticosteroids have been implicated in hippocampal atrophy in patients with severe psychiatric disorders, but little is known about receptor expression for corticosteroids in human or nonhuman primate brain. Both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were surveyed in this study of squirrel monkey brain using in situ hybridization histochemistry. Regions of high GR mRNA levels included CA1 and CA2 of hippocampus, dentate gyrus, paraventricular hypothalamus, lateral geniculate, lateral>medial amygdala, and cerebellum. Western analysis confirmed that GR immunoreactivity in squirrel monkey brain tissue most likely reflects the alpha isoform. Regions of high MR mRNA levels included all hippocampal pyramidal cell fields, dentate gyrus granule cell layer, lateral septum, medial>lateral amygdala, and to a lesser extent, cerebellum. Low levels of MR were also expressed in caudate and putamen. Receptor expression for corticosteroids in deep brain structures and the hippocampal formation was similar to that previously reported in rodents, but GR and MR mRNA were expressed at higher levels in squirrel monkey cerebral cortex. GR expression was evident in all cortical layers, particularly the pyramidal cell-rich layers II/III and V. MR expression was restricted to the more superficial cortical layers, and was only moderately represented in layer V. Laminar patterns were apparent in all regions of cortex for GR expression in squirrel monkeys, but low MR mRNA levels were found in dorsomedial prefrontal cortex (PFC). Different subregional distributions and distinctive laminar patterns suggest specialized functions or coordinated interactions between GR and MR mediated functions in primate PFC.
Biological Psychiatry | 2004
Paresh D. Patel; Crystal G. Pontrello; Sharon Burke
BACKGROUND Regulation of raphe serotonergic cells is fundamental to the prevailing hypothesis of major depression pathophysiology. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin biosynthesis, but brainstem TPH mRNA expression has been difficult to measure and study. Recently, a novel paralog of TPH, TPH2 (or neuronal TPH), was described, but its anatomic expression is unknown. METHODS In situ hybridization histochemical survey was conducted across Sprague-Dawley rat brain for TPH1 and TPH2 mRNA. Semiquantitative techniques were used to estimate relative mRNA levels in individual cells. RESULTS Almost exclusively, TPH2 mRNA is expressed in raphe, in a pattern overlapping the histologically defined raphe nuclei. In sharp contrast, TPH1 (the previously known TPH) is expressed predominantly in pineal gland. There is no appreciable overlap in the expression of these paralogs. The level of TPH2 mRNA expression in individual raphe cells is approximately 2.5-fold greater than the level of TPH1 expression in pinealocytes. CONCLUSIONS TPH2 mRNA has an anatomic expression pattern consistent with brainstem raphe nuclei and is likely to be the gene giving rise to the majority of TPH activity in these cells. The robust expression of TPH2 in brainstem should facilitate studies on the transcriptional regulation of raphe serotonin biosynthesis.
Neuroscience | 1996
Alfred Mansour; Sharon Burke; R.J. Pavlic; Huda Akil; S.J. Watson
Abstract Several lines of evidence have demonstrated the presence of three opioid receptor types in the CNS and periphery. These receptors are referred to as μ, δ and κ, and have been implicated in a wide variety of functions. The present study examines the localization of the κ 1 receptor-like protein using antibodies generated to the C terminal 42 amino acids of the cloned κ 1 receptor, a region of the receptor that has little homology with μ and b receptors. Immunohistochemical studies in Zamboni-fixed rat tissue demonstrate immunoreactive perikarya and/or fibers in such regions as the deep layers of the parietal, temporal and occipital cortex, parasubiculum, central and medial amygdala, bed nucleus stria terminalis, nucleus accumbens, olfactory tubercle, endopiriform nucleus, claustrum, hypothalamic nuclei, median eminence, midline thalamic nuclei, zona incerta, central gray, caudal linear and dorsal raphe, substantia nigra, pars reticulata, ventral tegmental area, parabrachial nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, spinal cord and the dorsal root ganglia. Specific κ 1 receptor-like immunohistochemical staining is also observed in the pituitary, where immunoreactive perikarya and fibers are localized in the neural and intermediate lobes. Transfection and preabsorption controls suggest that the antibody is selective for the cloned κ 1 receptor, and does not recognize μ or δ. This immunohistochemical localization corresponds well to previously described κ 1 receptor mRNA and binding distributions and provides new insights into the cellular localization and pre- and postsynaptic organization of the κ 1 receptor-like proteins in the rat brain and pituitary. The functional implications of these results are discussed in light of the role K, receptors play in hormonal regulation, antinociception and reward.
Journal of Psychiatric Research | 2013
Adriana Medina; Audrey F. Seasholtz; Vikram Sharma; Sharon Burke; William E. Bunney; Richard M. Myers; Alan F. Schatzberg; Huda Akil; Stanley J. Watson
Approximately 50% of mood disorder patients exhibit hypercortisolism. Cortisol normally exerts its functions in the CNS via binding to mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Both MR and GR are highly expressed in human hippocampus and several studies have suggested that alterations in the levels of MR or GR within this region may contribute to the dysregulation in major depressive disorder (MDD). Studies have also shown functional heterogeneity across the hippocampus, with posterior hippocampus preferentially involved in cognitive processes and anterior hippocampus involved in stress, emotion and affect. We therefore hypothesize that GR and MR expression in hippocampus of control and MDD patients may vary not only with disease, but also with regional specificity along the anterior/posterior axis. Students t-test analysis showed decreased expression of MR in the MDD group compared to controls in the anterior, but not the posterior hippocampus, with no significant changes in GR. Linear regression analysis showed a marked difference in MR:GR correlation between suicide and non-suicide patients in the posterior hippocampus. Our findings are consistent with previous reports of hippocampal corticosteroid receptor dysregulation in mood disorders, but extend those findings by analysis across the anterior/posterior axis of the hippocampus. A decrease in MR in the anterior but not posterior hippocampus of MDD patients emphasizes the important functional role of the anterior hippocampus in neuroendocrine regulation in humans.
Neuroscience Letters | 2003
Nakia S. Gordon; Sharon Burke; Huda Akil; Stanley J. Watson; Jaak Panksepp
Rough and tumble (R&T) play is assumed to have beneficial effects in developing organisms. To evaluate this idea, brain derived neurotrophic factor (BDNF) gene expression was evaluated in 32-day-old juvenile rats that were allowed to play for 30 min prior to sacrifice. In situ hybridization for BDNF mRNA revealed that the amygdala and dorsolateral frontal cortex had significantly elevated BDNF mRNA expression as a result of play. These effects suggest that play may help program higher brain regions involved in emotional behaviors.
Neuroscience | 1994
S. Petanceska; Sharon Burke; Stanley J. Watson; L. Devi
The cysteine lysosomal proteases comprise a large family of highly conserved enzymes which are essential for intracellular protein turnover. These proteases are very efficient in their ability to degrade components of the extracellular matrix, and have been implicated in processes of cell growth, malignant transformation and inflammation. There is also a growing body of evidence for their involvement in the metabolism of the amyloid precursor protein. The production of insoluble beta A4 amyloid peptide is thought to be one of the key events that lead to the development of Alzheimers pathology. To see the physiological role these enzymes play in the brain, we studied the relative abundance and distribution of the messenger RNAs for three lysosomal cysteine proteases, cathepsins B and L and cathepsin S, by in situ hybridization histochemistry in rat brain. All three enzymes are capable of degrading components of the extracellular matrix but they have different substrate preferences and resistances to neutral pH. We found that the mRNAs for cathepsins B, L, and S have different expression patterns in brain. Cathepsin B mRNA shows the highest level of expression. It has a wide distribution, and is preferentially expressed in neurons. The expression patterns of cathepsin B and cathepsin L mRNA overlap in many brain regions; in some areas they complement each other. Cathepsin B and L mRNAs are highly expressed in the choroid plexus, a structure that is instrumental in brain development. Both transcripts are also abundant in the neuropeptide synthesizing hypothalamic nuclei. Cathepsin S mRNA has wide expression pattern throughout brain, in grey and white matter. A great number of cells that express cathepsin S have microglial morphology. Regions that are known to contain the highest amounts of the amyloid precursor protein express highest levels of cathepsin B and cathepsin L mRNA. Also, all three transcripts are highly represented in regions that are most prone to degeneration in Alzheimers disease. These results suggest a role for these lysosomal hydrolases released from degenerating cells in the development of Alzheimers pathology.
PLOS Computational Biology | 2009
M. Kemal Sönmez; Naunihal T. Zaveri; Ilan A. Kerman; Sharon Burke; Charles R. Neal; Xinmin Xie; Stanley J. Watson; Lawrence Toll
We describe a computational framework that models spatial structure along the genomic sequence simultaneously with the temporal evolutionary path structure and show how such models can be used to discover new functional molecules through cross-genomic sequence comparisons. The framework incorporates a priori high-level knowledge of structural and evolutionary constraints in terms of a hierarchical grammar of evolutionary probabilistic models. In particular, we demonstrate a novel computational method for identifying novel prohormones and the processed peptide sites by producing sequence alignments across many species at the functional-element level. We present experimental results with an initial implementation of the algorithm used to identify potential prohormones by comparing the human and mouse proteins, resulting in high accuracy identification in a known set of proteins and a putative novel hormone from an unknown set. Finally, in order to validate the computational methodology, we present the basic molecular biological characterization of the novel putative peptide hormone, including identification in the brain and regional localizations. The success of this approach will have a great impact on our understanding of GPCRs and associated pathways, and help us identify new targets for drug development.