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K Chase

Publications and source records attributed to K Chase.

6 recordsLinked to original sources
PubMed1992

Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.

D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.

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PubMed1991

Immunoreactive calcium-binding protein (calbindin-D28k) in interneurons and trigeminothalamic neurons of the rat nucleus caudalis localized with peroxidase and immunogold methods.

Calbindin-D28k is a highly abundant protein found in neurons in selected brain regions, including cells in sensory systems of the brainstem. Because of its capacity to bind cytosolic Ca++, calbindin-D28k is thought to contribute to the regulation of compartmental Ca++ concentrations in neurons. In this study of the rat spinal trigeminal nucleus, calbindin-D28k was localized with immunoperoxidase and immunogold methods. Results showed that immunoreactive calbindin-D28k neurons were widely distributed to all regions of the nucleus, but were particularly numerous in the substantia gelatinosa. Some trigemino-thalamic neurons that were identified by retrograde labeling of a conjugated wheat-germ agglutinin with horseradish peroxidase also contained calbindin-D28k immunoreactivity. Most of the calbindin-D28k labeling was found in cell bodies and dendrites. Axon terminals were rarely stained. More discrete labeling with a gold-conjugated second antibody showed that the predominant site of calbindin-D28k was the matrix of the cytoplasm. Gold label was also heavily associated with euchromatin within nuclei. These findings show that immunoreactive calbindin-D28k is localized to both interneurons and projecting neurons of the spinal trigeminal nucleus. Many of these cells are likely to receive glutamatergic afferent inputs, which may act in part by increasing Ca++ flux into the neurons. Calbindin-D28k has a high capacity for buffering Ca++ and under some conditions may protect neurons against glutamate-induced excitotoxicity. We speculate that calbindin-D28k may function to regulate calcium concentrations in spinal trigeminal neurons.

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PubMed1991

N-methyl-D-aspartate receptor activation in the neostriatum increases c-fos and fos-related antigens selectively in medium-sized neurons.

In the neostriatum a selective loss of neurons occurs following exposure to N-methyl-D-aspartate receptor agonists. One hypothesis emerging from this observation is that an excitotoxic process via N-methyl-D-aspartate receptors may contribute to the pathogenesis of Huntington's disease, which is characterized by the loss of medium-sized neurons. However, whether there is a selective distribution of N-methyl-D-aspartate receptors in specific populations of neostriatal neurons is unknown. In this study the expression of c-fos mRNA and protein was used to examine the response of neostriatal cells to N-methyl-D-aspartate receptor stimulation in the rat. After intrastriatal injection of the N-methyl-D-aspartate receptor agonist, quinolinic acid, an increase in c-fos mRNA concentrations was detected using in situ hybridization and Northern blot analysis. Western blot analysis showed that not only the c-Fos mRNA protein product but also other Fos-related antigens capable of binding to DNA were increased in response to N-methyl-D-aspartate receptor activation. The selectivity of the neuronal response to N-methyl-D-aspartate receptor activation was examined immunohistochemically at the light and ultrastructural levels. Our results indicate that N-methyl-D-aspartate receptor activation by quinolinic acid stimulates medium spiny neurons to increase c-Fos expression; to a lesser extent, medium aspiny interneurons and glial cells also respond. In contrast, negligible change in c-Fos expression is observed in large neurons. These results are consistent with other evidence that medium-sized spiny neurons are preferentially vulnerable to the toxic effects of excitatory amino acids acting at N-methyl-D-aspartate receptors. An additional implication of these findings is that activation of the N-methyl-D-aspartate receptor in medium spiny neurons leads to increased expression of candidate AP-1 transcription factors, thereby coupling the N-methyl-D-aspartate receptor and regulation of gene expression in signal transduction processes of the neostriatal medium spiny neuron.

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PubMed1988

Hypothyroidism increases substance P concentrations in the heterotopic anterior pituitary.

The regulatory effects of thyroid hormone on adenohypophysial substance P (SP) were studied in heterotopically implanted anterior pituitaries. Three or four anterior pituitaries from 21-day-old rat pups were implanted under the renal capsule in 175- to 200-g adult rats. The donor and recipient animals were sex matched. One week after implantation, animals were thyroidectomized or sham operated. A separate group of animals received daily T4 treatment (1.5 g/100 g, ip). After 2 weeks, the native and heterotopic pituitaries were assayed for SP, TSH, PRL, and LH. Thyroidectomy resulted in a 3- to 10-fold increase in the SP concentration in both the heterotopic and native pituitaries compared to euthyroid values. T4 treatment suppressed the SP levels in the heterotopic pituitaries of the thyroidectomized rats. In contrast to the reduction of TSH concentrations in native pituitaries in thyroidectomized animals vs. controls, TSH concentrations in the heterotopic pituitaries of thyroidectomized rats were approximately 10 times greater than those in euthyroid animals. PRL concentrations were unaffected by hypothyroidism in native and heterotopic pituitaries. Thyroidectomy resulted in a decrease in LH concentrations in the native anterior pituitary, without affecting LH concentrations in the implanted pituitary. These findings indicate that a direct link from the hypothalamus to the anterior pituitary is not required for the pituitary SP response to hypothyroidism.

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PubMed1986

Glutamic acid decarboxylase and enkephalin immunoreactive axon terminals in the rat neostriatum synapse with striatonigral neurons.

Synaptic interactions between striatal projection neurons and axon terminals containing immunoreactive glutamic acid decarboxylase (GAD) or Leu-enkephalin were examined in the rat neostriatum using a combined method of horseradish peroxidase retrograde transport from the substantia nigra and immunohistochemistry at the electron microscopic level. Results showed that numerous immunoreactive GAD and enkephalin boutons formed synapses with the cell bodies and dendrites of medium-sized striatonigral neurons. These findings demonstrate that within the neostriatum GABA and enkephalin directly influence caudate output pathways.

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