Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The APC gene was identified in 1991 at chromosome 5 q 21, which is responsible for the familial adenomatous polyposis (FAP). The gene has been classified as one of the tumor suppressor genes. The APC gene mutations were suggested to initiate sporadic as well as inherited colorectal neoplasia and to be related to mental retardation. The different forms of APC gene expression and their association to carcinogenesis have been carefully studied. However, the function of APC gene in the central nervous system has not been known. In this study, on the basis of the cDNA cloning of APC homologue in the guinea pig by Dr. Fan Meng, we rescued this fragment including the full length encoding region from plasmid pMe 18s and then subcloned it into the polylink site of the plasmid pBluscript KS. Both digoxigenin labeled sense and anti-sense RNA were synthesized by in vitro transcription. RNase protection assay and in situ hybridization enable us to examine the distribution of APC transcripts in guinea pig brain. Strong signals were detected in hippocampus. APC mRNA was mainly localized in the pyramidal neurons of CA 1, CA 3, as well as in the dentate granule cells; the cerebellum granular cells also showed strong staining; in the cerebrum, the parietal and primary olfactory cortex showed stronger signals than the frontal cortex; in olfactory bulb, positive cells with strong signals were observed: the brain stem showed a relatively weaker staining. Very similar expression pattern was also shown in embryonic guinea pig brain; except that the expression of APC gene in frontal cortex and olfactory bulb was stronger than that in adult animals. The results suggest that the APC transcripts in brain may play an important role during the early development of the central nervous system. Further study may enable us to take a deeper insight into the mechanism underlying inherited mental deficiency.
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PMID:[The distribution of tumor suppressor gene APC mRNA in guinea pig brain]. 857 9

Information from most of the sensory modalities enters the amygdala via the lateral nucleus. The olfactory information, however, arrives at the amygdala through the superficial nuclei, including the periamygdaloid cortex. To find out whether the olfactory information can modulate the processing of sensory information in the lateral nucleus we injected Phaseolus vulgaris leucoagglutinin, an anterograde axonal tracer, into the different divisions of the periamygdaloid cortex. We found that the PAC division of the periamygdaloid cortex projects to the ventrolateral and medial divisions, but not the dorsolateral division, of the lateral amygdaloid nucleus. Therefore, the projection from the PAC to the lateral nucleus provides a route, by which the olfactory information may become associated with other sensory modalities. Also, together with our previous finding that the lateral nucleus projects to the periamygdaloid cortex, the present data demonstrate that the lateral nucleus and the PAC are reciprocally connected.
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PMID:Topographic projections from the periamygdaloid cortex to select subregions of the lateral nucleus of the amygdala in the rat. 881 67

The role of the associative connections in the propagation of epileptiform discharges originating from an acute, localized epileptic focus in the anterior piriform cortex has been characterized recently in the in vitro isolated guinea-pig brain preparation. The present study demonstrates that the dorsal propagation of epileptiform synaptic potentials generated in APC is carried by long-projective associative fibres. Current source density analysis of the field potential profiles evoked by stimulation of the lateral olfactory tract has been utilized to describe the functional circuit activated in rostral and caudal regions of the piriform cortex, before and after the induction of a bicuculline epileptic focus in the anterior piriform cortex. Separate stimulation of the lateral olfactory tract at two sites, caudal and rostral to a tract incision, activates epileptiform potentials that are generated at the site of primary focus in the anterior piriform cortex and travel along associative fibres. Selective cutting of the long-projective associative fibres abolishes the epileptic associative potential in the cortical regions caudal to the section. The present study demonstrates directly that epileptiform potentials propagate along associative fibres to cortical regions that are synaptically related to the focus of origin. Such a pattern of propagation may sustain the generation of secondary foci in cortical regions remote from the primary epileptic focus.
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PMID:Propagation of epileptiform potentials in the guinea-pig piriform cortex is sustained by associative fibres. 883 90

The present study was undertaken in order to study the effects of perinatal asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and dopamine metabolites (3,4-dihydroxyphenylacetic acid, DOPAC, homovanillic acid, HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid chromatography, HPLC) measured in the basal ganglia of the 20- to 40-min-old newborn and 4-week-old male rat. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from pregnant rats at full term, in a 37 degrees C water bath for 15-16 min or 19-20 min. Following asphyxia, the uterus horns were opened, and the pups were removed and stimulated to breathe. A 100% and 50-80% pup survival was obtained following 15-16 min and 19-20 min of asphyxia, respectively. Acute changes were studied in brains from newborn pups 20-40 min after delivery, and long-term changes were studied in brains from 4-week-old rats. No changes in TH-activity could be observed in the substantia nigra/ventral tegmental area (SN/VTA), the striatum, or the accumbens nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In the newborn rat, 19-20 min of asphyxia increased (as compared to controls) dopamine levels in the SN/VTA to 136 +/- 14% and in the ACC/TUB to 160 +/- 10%, indicating an increased synthesis and/or release of dopamine. DO-PAC levels were increased in the SN/VTA to 150 +/- 14% and in the ACC/TUB to 151 +/- 10%, and HVA levels were increased to 152 +/- 16% in the striatum and to 117 +/- 4% in the ACC/TUB. Following 15-16 min of asphyxia, dopamine levels were increased to 130 +/- 12% in the ACC/TUB, and DOPAC levels were increased to 135 +/- 6% and 130 +/- 12% in the SN/VTA and the ACC/TUB, respectively. This suggests that the increased dopamine levels may preferably reflect an increased release of dopamine following perinatal asphyxia. In the 4-week-old rat, dopamine levels were decreased in the SN/VTA to 71 +/- 4%, in the striatum to 52 +/- 8%, and in the ACC/TUB to 53 +/- 7%, following 19-20 min of perinatal asphyxia as compared to controls. No changes were observed in DOPAC, HVA, or 3-MT levels, indicating that the reduced dopamine levels reflect a reduced dopamine synthesis following perinatal asphyxia. A decrease in dopamine utilization was observed in the striatum to 15 +/- 8% and in the ACC/TUB to 9 +/- 13% following 19-20 min of perinatal asphyxia as compared to controls. This indicates that perinatal asphyxia produced long-lasting reductions in activity in the mesostriatal/mesolimbic dopamine systems in the 4-week-old rat.
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PMID:Effects of perinatal asphyxia on the mesostriatal/mesolimbic dopamine system of neonatal and 4-week-old male rats. 900 42

Recent biochemical studies have demonstrated that the adenomatous polyposis coli gene, initially identified via its link to colon cancer, is expressed at high levels in the brain. Furthermore, the ability of this tumor suppressor protein to bind to Discs-Large and beta-catenin, proteins implicated in organizing synaptic structure, point to a role for APC in neuronal signalling. However, anatomical studies have provided conflicting results regarding its localization in brain. In situ hybridization studies predict neuronal expression of APC, while immunostaining studies performed with a panel of N-terminal antibodies detected staining of glial cells, especially oligodendrocytes. In this study, we have examined the basis for this discrepancy and provide evidence that the glial staining pattern detected in previous studies reflects cross-reactivity with an unrelated antigen rather than the localization of APC. Furthermore, we have performed immunohistochemical studies with a C-terminal APC antibody which reveal a neuronal pattern of staining closely matching that predicted by the in situ studies. For example, in the hippocampus APC immunostaining is detected in the pyramidal neurons and dentate granule cells, which fits well with the localization of APC mRNA. Examination of APC immunostaining in other regions revealed that particularly intense staining was displayed by large neurons, including layer V cortical pyramidal neurons, cerebellar Purkinje cells, and olfactory bulb mitral cells. Within labeled neurons, APC staining was apparent in the cytoplasm, as well as in dendritic and axonal processes. To help clarify the localization of APC in brain, we have conducted additional in situ hybridization and immunohistochemical studies. These results provide compelling evidence that APC is expressed predominantly in neurons rather than in glial cells as reported previously.
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PMID:Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein. 1036 23

Although, since the isolation of pituitary adenylate cyclase-activating polypeptide (PACAP), a wealth of literature has been published describing its localization, binding sites, and biological activities in a variety of mammalian tissues, only very little is known about PACAP in avian species. Therefore, in order to find out the sites of actions of PACAP and to elucidate its physiological significance in birds, we identified a chicken PACAP receptor homologue of the mammalian type I receptors (PAC(1)-Rs). The chicken PACAP type I cDNA sequence was obtained using reverse transcriptase-polymerase chain reaction (RT-PCR) in combination with 3'- and 5'-RACE PCR. This cDNA encodes a 471 amino acid precursor protein, sharing 81-83% sequence identity with mammalian analogs and 76% amino acid identity with the goldfish type I PACAP receptor. Northern blot analysis of chicken brain poly(A)(+)-rich RNA revealed the presence of a 5.5 kb and 7.5 kb PAC(1) receptor transcript. RT-PCR revealed that the chicken PACAP receptor is mainly expressed in the brain and gonads. A smaller amount of the receptor mRNA was found in pituitary, adrenal gland, kidney, intestine, pancreas, lung, and heart tissue. In situ hybridization with specific antisense oligodeoxynucleotide probes showed a widespread distribution of PAC(1) receptor mRNA in the chicken brain, with the highest expression being found in the dorsal telencephalon, olfactory bulb, hypothalamus, optic tectum, and cerebellar cortex. These findings suggest that PACAP affect a variety of functions both in the brain and peripheral tissues of the chicken.
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PMID:Molecular cloning and expression of a chicken pituitary adenylate cyclase-activating polypeptide receptor. 1052 79

This experiment determined the importance of functional coupling between structures of central olfactory pathways: the olfactory bulb (OB), anterior (APC), posterior (PPC) parts of the piriform cortex and lateral entorhinal cortex (EC). From local field potential signals obtained in awake rats, coupling during spontaneous activity was estimated with variables reflecting level of coherence computed with a dynamical method. Results revealed a clear hierarchy in the strength of coupling between structures with dissociation within the piriform cortex: PPC was more tightly coupled with the EC than with APC. Systemic injection of a cholinergic antagonist, scopolamine, suggested that tonic coupling is strongly mediated by cortico-cortical connections and not by an external synchronizer, except between OB and APC.
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PMID:Functional coupling in rat central olfactory pathways: a coherence analysis. 1058 64

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide and its specific receptor (the PAC(1) receptor) is widely distributed in the rat brain. It has been reported that alternative splicing of the region encoding the third intracellular loop of the PAC(1) receptor generates six isoforms which are differentially coupled to signal transduction pathways, but the precise distribution and localization of these splice isoforms in the brain remain to be determined. Using the initial specific primer pairs which correspond to the 'hip' or 'hop' types of receptors for the solution-phase reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated that the major splice variants of the PAC(1) receptor in various regions of the rat brain are the short splice isoform 'PAC(1)-R-s' which does not contain either the 'hip' or 'hop' cassette and the another splice isoform, 'PAC(1)-R-hop', which contains the 'hop' cassette. With an innovative molecular histochemical technique, in situ RT-PCR, we determined that these two splice isoforms are both intensely expressed in the mitral cells of the olfactory bulb, the Purkinje cells of the cerebellum, the pyramidal cells of the hippocampus and neocortex, and many neurons in the nuclei of hypothalamus and thalamus as well as other regions. The initial mapping of the cell type-specific expression of these two splice variants of the PAC(1) receptor provides the basis for a better understanding of the functional significance of the PAC(1)-R and its ligand PACAP in various brain regions.
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PMID:Cellular distribution of the splice variants of the receptor for pituitary adenylate cyclase-activating polypeptide (PAC(1)-R) in the rat brain by in situ RT-PCR. 1064 99

As the brain develops, a homogeneous population of mitotically active progenitors generates the molecularly heterogeneous post-mitotic cells of the mature brain. The balance between cell division, growth arrest and differentiation of these progenitors undoubtedly requires the activation of a vast array of genes. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. Within the nervous system, PACAP has been shown to stimulate neurite outgrowth, regulate neurotransmitter production and neuronal survival. These diverse biological actions are mediated through interaction with two types of receptors, a PACAP-selective receptor (PAC(1)-R) and receptors which interact almost equally with both VIP and PACAP. Since several lines of evidence suggest that PACAP acts as a neurotrophic factor, we sought to characterize PACAP and PAC(1)-R expression in the developing rat nervous system. The PAC(1)-R is expressed at very high levels in ventricular zones throughout the neuraxis. In addition to the embryonic enrichment in proliferative zones, PAC(1)-R expression is maintained in areas of neurogenesis in the adult central nervous system (CNS), namely, the subventricular zone of the olfactory bulb and hippocampal dentate gyrus. In contrast, PACAP is expressed primarily in the post-mitotic parenchyma. This temporal regulation and cellular distribution suggests that PACAP, through its interaction with the PAC(1)-R, may play a role in mammalian neurogenesis.
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PMID:Developmental regulation of pituitary adenylate cyclase-activating polypeptide and PAC(1) receptor mRNA expression in the rat central nervous system. 1072 27

To map in detail the brain areas in which pituitary adenylate cyclase-activating polypeptide (PACAP) may play a significant role in birds, the distribution of PACAP and PACAP type I receptor (PAC(1)-R) mRNA was examined throughout the entire chicken brain by using in situ hybridization histochemistry. Widespread distribution of both PACAP and its receptor mRNA was found. The telencephalic areas where the most intense signals for PACAP mRNA were found included the hyperstriatum accessorium, the hippocampus, and the archistriatum. In the diencephalon, a group of neurons that highly expressed PACAP mRNA was observed from the anterior medial hypothalamic nucleus to the inferior hypothalamic nucleus. Moderate expression was found in the paraventricular nucleus and the preoptic region. A second large group of neurons containing PACAP message was found within the nucleus dorsolateralis anterior thalami and extended caudally to the area around the nucleus ovoidalis and the nucleus paramedianus internus thalami. Furthermore, expression of PACAP message was observed within the bed nucleus of the pallial commissure, nucleus spiriformis medialis, optic tectum, cerebellar cortex, olfactory bulbs, and several nuclei within the brainstem (dorsal vagal and parabrachial complex, reticular formation). The highest expression of PAC(1)-R mRNA was found in the dorsal telencephalon, olfactory bulbs, lateral septum, optic tectum, cerebellum, and throughout the hypothalamus and thalamus. The presence of PACAP and PAC(1)-R mRNA in a variety of brain areas in birds suggests that PACAP mediates several physiologically important processes in addition to regulating the activity of the pituitary gland.
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PMID:Distribution of pituitary adenylate cyclase-activating polypeptide and pituitary adenylate cyclase-activating polypeptide type I receptor mRNA in the chicken brain. 1086 37


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