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W E Cullinan

Publications and source records attributed to W E Cullinan.

27 records · Page 2Linked to original sources
PubMed1993

Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis.

Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non-neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing.

Animals↗
PubMed1992

Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression.

The hippocampus appears to be involved in tonic regulation of the hypothalamo-pituitary-adrenocortical axis via interactions with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular nucleus (PVN). To further investigate the anatomical basis of such interactions, lesions were made to forebrain fiber tracts in position to communicate inhibitory information from the hippocampus to the PVN. Total fimbria-fornix transections (TFF) and lateral fimbria-fornix lesions (LFF) both significantly increased CRH mRNA levels in the medial parvocellular PVN, as assayed by semi-quantitative in situ hybridization histochemistry. Medial fimbria-fornix lesions or section of the medial corticohypothalamic tracts (MCHT) did not influence CRH mRNA levels. The LFF group showed increases in both AVP mRNA and ACTH secretion, whereas no other lesion was effective in this regard. The results suggest: (1) hippocampal efferents conferring tonic inhibition of the HPA axis probably originate in regions contributing to the lateral extent of the fornix, representing structures in the ventral subiculum and ventral extent of CA1; (2) projections from the hippocampus to the medial basal hypothalamus (travelling in the MCHT) are unlikely to affect HPA function; (3) hippocampus may influence the PVN CRH/AVP neuron at multiple levels, in that LFF and TFF lesions have differential effects on PVN AVP mRNA levels and ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1992

Projections from the nucleus accumbens to cholinergic neurons of the ventral pallidum: a correlated light and electron microscopic double-immunolabeling study in rat.

A correlated light- and electron microscopic double-immunolabeling study combining choline acetyltransferase immunocytochemistry with anterograde tracing of Phaseolus vulgaris leucoagglutinin (PHA-L) revealed that axons of the nucleus accumbens terminate on cholinergic neurons of the ventral pallidum. These findings are discussed with respect to the possibility that these cholinergic neurons may be part of parallel circuits, providing feedback to the same cortical and amygdaloid areas which innervate the nucleus accumbens.

Acetylcholine↗
PubMed1991

Organization of ascending hypothalamic projections to the rostral forebrain with special reference to the innervation of cholinergic projection neurons.

Axonal projections from hypothalamic nuclei to the basal forebrain, and their relation to cholinergic projection neurons in particular, were studied in the rat by using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with choline acetyltransferase (ChAT) immunocytochemistry. Discrete iontophoretic PHA-L injections were delivered to different portions of the caudal lateral hypothalamus, as well as to various medial hypothalamic areas, including the ventromedial, dorsomedial, and paraventricular nuclei, and anterior hypothalamic and medial preoptic areas. The simultaneous detection of PHA-L-labeled fibers/terminals and ChAT-positive neurons was performed by using nickel-enhanced diaminobenzidine (DAB) and nonenhanced DAB as chromogens. Selected cases were investigated at the electron microscopic level. Ascending hypothalamic projections maintained an orderly lateromedial arrangement within the different components of the medial forebrain bundle, as well as with respect to their terminal projection fields (e.g., within the bed nucleus of the stria terminalis and lateral septal nucleus). The distribution pattern of hypothalamic inputs to cholinergic projection neurons corresponded to the topography of ascending hypothalamic axons. Axons originating from neurons in the far-lateral hypothalamus reached cholinergic neurons in a zone that extended from the dorsal part of the sublenticular substantia innominata (SI) caudolaterally, to the lateral portion of the bed nucleus of the stria terminalis rostromedially, encompassing a narrow band along the ventral part of the globus pallidus and medial portion of the internal capsule. Axons originating from cells in the medial portion of the lateral hypothalamus reached cholinergic cells primarily in more medial and ventral parts of the SI, and in the magnocellular preoptic nucleus and horizontal limb of the diagonal band nucleus (HDB). Axons from medial hypothalamic cells appeared to contact cholinergic neurons primarily in the medial part of the HDB, and in the medial septum/vertical limb of the diagonal band complex. Electron microscopic double-labeling experiments confirmed contacts between labeled terminals and cholinergic cells in the HDB and SI. Individual hypothalamic axons established synapses with both cholinergic and noncholinergic neuronal elements in the same regions. These findings have important implications for our understanding of the organization of afferents to the basal forebrain cholinergic projection system.

Afferent Pathways↗
PubMed1991

Neuroanatomical and functional studies of peptide precursor-processing enzymes.

An overview of in situ hybridization mapping studies comparing the brain distributions of mRNA transcripts encoding the proprotein convertase Furin, PC1 and PC2 in relation to transcripts encoding carboxypeptidase H (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) is presented. Furin mRNA was detected in both neurons and non-neuronal cells throughout all brain areas. The cellular localization of PC1 and PC2 was primarily neuronal, with PC2 generally more widely distributed, although many regional variations were detected. The detection of specific combinations of the convertases, CPE and PAM in peptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide processing. Results are also described from a series of functional studies on the processing of pro-opiomelanocortin (POMC) in a heterologous neuronal cell line, Neuro-2A, which expresses low levels of PC2 mRNA but no detectable PC1 mRNA. Two contrasting POMC-processing patterns were observed: one where the precursor was processed at a number of cleavage sites to produce several peptides, and another where POMC was processed at a single cleavage site to produce beta E only. If PC2 is responsible for POMC processing in transfected cells, this enzyme may have favored cleavage of the amino terminal-processing site above other sites in the latter type of cell line.

Animals↗
PubMed1989

Hypothalamic axons terminate on forebrain cholinergic neurons: an ultrastructural double-labeling study using PHA-L tracing and ChAT immunocytochemistry.

A correlated light and electron microscopic study combining choline acetyltransferase immunocytochemistry with anterograde tracing of Phaseolus vulgaris leucoagglutinin revealed that axons of lateral hypothalamic neurons terminate on forebrain cholinergic projection cells. This finding is discussed in relation to direct and indirect corticopetal systems.

Animals↗
PubMed1987

Unilateral odor deprivation: effects on the development of staining for olfactory bulb succinate dehydrogenase.

Littermate rat pups underwent either unilateral surgical occlusion of the right external naris or sham surgery on postnatal Day 1. At 4-, 8-, 12-, 20- or 30-days postpartum, olfactory bulb sections were histochemically reacted to reveal either succinate dehydrogenase (SDH) or cytochrome oxidase (CO) activity. Microdensitometry was used to determine levels of staining in glomeruli and the external plexiform layer at standardized locations within the bulb. In experimental subjects asymmetries in left/right bulb SDH staining patterns were detected as early as Day 4, suggesting that the deprivation procedure resulted in quite rapid changes in the metabolic function of olfactory bulb cells. Control animals did not exhibit left/right differences in bulb staining, but inter-glomerular and regional variations in staining were observed throughout the early developmental period. Understanding these early variations in metabolic activity may be important for a complete understanding of olfactory bulb maturation.

Animals↗