{"title":"The non-neurogenic catecholamine response of the fetal adrenal to hypoxia is dependent on activation of voltage sensitive Ca2+ channels.","authors":"M B Adams, G Simonetta, I C McMillen","doi":"10.1016/0165-3806(96)00054-5","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00054-5","url":null,"abstract":"<p><p>We have investigated the cellular mechanisms underlying the catecholamine response of the fetal sheep adrenal to hypoxia before and after the development of adrenal innervation. Adrenals were collected before (80-100 days gestation: n = 7) and after (135-146 days gestation: n = 10) development of innervation and retrogradely perfused with oxygenated Krebs bicarbonate buffer in vitro via the renal vein. Adrenal hypoxia was induced by perfusion with hypoxic Krebs buffer (pO2 = 46.7 +/- 2.4 mm Hg) for 30 min periods in the presence and absence of hexamethonium (500 microM), Ca2+ (2.5 mM), nifedipine (1 microM) and KCl (10 mM). Hypoxia stimulated an increase (P < 0.001) in the output of noradrenaline at 80-100 days (3 min pre hypoxia, 0.18 +/- 0.07 nmol/3 min; 20 min hypoxia, 0.74 +/- 0.22 nmol/3 min) and at 135-146 days (3 min pre hypoxia, 0.53 +/- 0.20 nmol/3 min; 20 min hypoxia, 1.71 +/- 0.85 nmol/3 min). Adrenaline output was also higher (P < 0.001) than basal values (80-100 days, 0.11 +/- 0.06 nmol/3 min; 135-146 days, 0.53 +/- 0.15 nmol/3 min) after 20 min hypoxia (0.41 +/- 0.20 nmol/3 min and 1.35 +/- 0.56 nmol/3 min respectively). The catecholamine responses to hypoxia were abolished by removal of Ca2+ from the adrenal perfusate. There was a reduction (P < 0.05) in the catecholamine secretory response to hypoxia in the presence of nifedipine. Noradrenaline output decreased from 4.33 +/- 0.84 nmol/30 min to 0.16 +/- 0.49 nmol/30 min and adrenaline output decreased from 3.16 +/- 1.66 nmol/30 min to -0.01 +/- 0.24 nmol/30 min in the presence of nifedipine. The fetal adrenal secretes catecholamines by a direct or non-neurogenic mechanism in response to hypoxia. This secretory response is dependent on the activation of voltage sensitive Ca2+ channels in the chromaffin cell membrane.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"182-9"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00054-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19804090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Developmental profile and regulation of estrogen receptor (ER) mRNA expression in the preoptic area of prenatal rats.","authors":"L L DonCarlos","doi":"10.1016/0165-3806(96)00067-3","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00067-3","url":null,"abstract":"<p><p>Estrogen, derived from circulating testosterone, masculinizes the developing preoptic area. Expression of estrogen receptors (ERs) within the preoptic area is one requirement for a possible direct action of estrogen in the process of sexual differentiation of this brain region. Using a 35S-labeled riboprobe and in situ hybridization to detect ER mRNA on both film and emulsion-coated slides, we were able to detect ER mRNA within the rat preoptic area by embryonic day 18 (ED 18), coincident with the reported onset of the critical period for testosterone-dependent masculinization of this region. ER mRNA increased significantly between ED 18 and 19 in both sexes, and continued to increase through postnatal day 0 (PND 0 = day of birth) in females, but not males. ER mRNA levels were not significantly greater in females than in males until PND 0. The lack of a sex difference in ER mRNA prenatally, however, appears to be due to an effect of intrauterine neighbors. ER mRNA levels in ED 20 embryos were relatively high in females with female-only neighbors, whereas ER mRNA levels were relatively low, and comparable to males, when the in utero neighbors included one or more males. Treatment of pregnant dams with diethylstilbestrol or with tamoxifen did not significantly alter ER mRNA levels in the preoptic area of the embryos. Although these results suggest that ER mRNA expression is subject to hormonal regulation prenatally, the relevant hormone was not identified.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"224-33"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00067-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19805162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early postnatal lesions of the substantia nigra produce massive shrinkage of the rat striatum, disruption of patch neuron distribution, but no loss of patch neurons.","authors":"D van der Kooy","doi":"10.1016/0165-3806(96)00062-4","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00062-4","url":null,"abstract":"<p><p>Unilateral lesions of the substantia nigra in the first postnatal week cause a massive shrinkage (> 50%) of the ipsilateral rat striatum, due primarily to neuronal cell death. Striatal patch neurons (marked by retrograde labeling from the substantia nigra prior to the lesions) selectively survive the striatal cell death caused by the lesions. However, after the lesions these early retrogradely labeled patch neurons are distributed diffusely through the remaining striatum, in contrast to their normal patchy distribution throughout the postnatal period. Thus, many striatal neurons (but not the patch and matrix neurons with early axonal projections to the substantia nigra) are critically dependent upon interactions with the substantia nigra for their survival during the early postnatal period, and in the absence of these missing striatal and substantia nigra neurons, the remaining striatal patch neurons are no longer distributed in a patchy fashion.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"242-5"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00062-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19805165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of striatal dopaminergic function. I. Pre- and postnatal development of mRNAs and binding sites for striatal D1 (D1a) and D2 (D2a) receptors.","authors":"A B Jung, J P Bennett","doi":"10.1016/0165-3806(96)00033-8","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00033-8","url":null,"abstract":"<p><p>Quantitative receptor autoradiography with iodinated ligands, quantitative in situ hybridization histochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to describe the prenatal and early postnatal ontogeny (embryonic day 14 to postnatal day 7, or E14 to P7) of striatal D1 and D2 dopamine receptor binding sites and mRNA levels, respectively, in relation to the development of dopaminergic nigrostriatal innervation D1 dopamine receptor, measured by [125I]SCH23982 binding, and dopamine transporter binding sites, measured by [125I]RTI-55 binding, were present in low amounts beginning on E14 (2-3% and 0.3-0.6% of adult values, respectively) and increased slowly during the prenatal period. D2 receptor binding sites, measured with [125I]spiperone, were also detected on E14 but in higher relative quantities (17% of adult values) than D1 receptor and dopamine transporter binding sites at the same age. Other than abrupt declines in the late prenatal period for D1 and D2 receptor binding sites, all three binding sites increased throughout development and increased maximally between P7 and adulthood. On P5, both D1 and D2 receptors were functionally coupled to their respective G proteins, based on GTP-induced decreases in affinity of dopamine for [125I]SCH23982 and [125I]spiperone binding. D1 receptor mRNA was present in E14 striatal anlage, increased prenatally, declined on P0, then increased to a peak on P5, after which it declined to its lowest levels (20% of peak values) in the adult. In contrast, D2 receptor mRNA levels were presented also on E14, increased to a peak on P0, declined until P5, and increased thereafter to adulthood. Anatomically, nigrostriatal innervation and D1 and D2 receptor mRNA levels increased from the medial to lateral striatal quadrants. In contrast, D1 and D2 receptor binding site ontogency exhibited fairly homogenous distributions from E18 to P7. D1 and D2 receptor mRNAs appear to be expressed early in prenatal development before there is any significant dopaminergic innervation. In contrast, the majority of D1 and D2 receptor binding activity, representing expressed receptor proteins, develops in the postnatal period and correlates well with the increase in dopaminergic innervation. Intrinsic genetic programming is more likely to be responsible for D1 and D2 receptor gene transcription in striatal neuroblasts and newly born neurons, while factors derived from ingrowing dopaminergic afferents may direct post-transcriptional dopamine receptor development. The dissociation between the ontogeny of dopamine receptor binding sites and mRNAs suggests that the developmental regulation of D1 and D2 receptor synthesis is independent of D1 and D2 receptor gene transcription.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"109-20"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00033-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19803579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A transient phase of cell death in the developing medial forebrain of the perinatal ferret.","authors":"J K Johnson, N E Berman","doi":"10.1016/0165-3806(96)00042-9","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00042-9","url":null,"abstract":"<p><p>A transient bilateral population of cells immediately rostral to the ferret corpus callosum was examined at weekly intervals between embryonic day 28 and postnatal day 7. This region is tentatively identified as the medial forebrain apoptosis zone (MFAZ) because of the specific nature of cell death, and the limited area or zone in which it was observed. No other region within the brain or retina exhibited a similar pattern or amount of cell death. Only scattered apoptotic cells were found throughout the remainder of the brain-including the cerebral cortical plate, subplate, and white matter-with the exception of the ventricular zone of the lateral ventricles which contained a significant population of apoptotic cells. This study addressed three questions about apoptosis in the MFAZ: (1) does apoptotic cell death in this region signal the appearance of phagocytic macrophages, (2) does cell degeneration and phagocytosis in this region lead to the formation of an extracellular space analogous to the cavum septi pellucidi of rodents, and (3) what is the duration of degeneration, or clearance rate, of cell death in this defined region. The MFAZ was first found to contain apoptotic nuclei and macrophages late in gestation, at E34. Numbers of apoptotic nuclei and macrophages peaked one week later at birth in this area, but disappeared early in postnatal life. During this period, formation of a space rostral to the corpus callosum due to the removal of apoptotic cells was not observed. Finally, presence of apoptotic cells in the MFAZ over a period of > or = 9 days suggests a clearance rate of many hours. The close spatiotemporal correlation of the distribution of apoptotic cells and their removal by macrophages suggests that these are interrelated, and perhaps interdependent events.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"159-65"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00042-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19804087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vivo and in vitro expression of rat galactose-1-phosphate uridyltransferase (GALT) in the developing central and peripheral nervous system.","authors":"N Daude, E Ellie, J K Reichardt, K G Petry","doi":"10.1016/0165-3806(96)00058-2","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00058-2","url":null,"abstract":"<p><p>Galactose-1-phosphate uridyltransferase (GALT) is a key enzyme in the metabolism of galactose. GALT activates the galactose-glucose interconversion and enables the synthesis of glucose-1-phosphate and UDP-galactose (UDP-Gal). UDP-Gal is the galactosyl donor for the incorporation of galactose into complex oligosaccharides, glycoproteins and glycolipids. The expression of GALT was characterized both in vivo and in vitro during late embryonic and postnatal development of the brain and peripheral nerve of the rat. Assays of GALT mRNA and protein showed that it is weakly expressed during late embryonic development with a second peak of expression concomitant with myelinogenesis. GALT was prominently expressed in myelinating Schwann cells in a rat dorsal root ganglia culture system. GALT deficiency in humans results in galactosemia, a disease characterized by long-term intellectual impairment, and probably dysmyelination. The developmentally regulated pattern of GALT expression during maturation of the nervous system may provide a molecular basis for these neurological complications which seriously compromise the outcome of many galactosemic patients.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"190-6"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00058-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19805159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of striatal dopaminergic function. II: Dopaminergic regulation of transcription of the immediate early gene zif268 and of D1 (D1a) and D2 (D2a) receptors during pre- and postnatal development.","authors":"A B Jung, J P Bennett","doi":"10.1016/0165-3806(96)00034-x","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00034-x","url":null,"abstract":"<p><p>We investigated cocaine- and apomorphine-mediated induction of the zinc finger immediate early gene (IEG), zif268, during striatal ontogeny. Acute cocaine or apomorphine treatment increased striatal zif268 mRNA on embryonic day 20 (E20), postnatal day 5 (P5), and in adults, but not on E15, with developmentally distinct anatomical profiles. SCH23390 pretreatment completely attenuated zif268 gene expression at all ages, but eticlopride treatment of E20 and P5 rats prior to cocaine enhanced zif268 expression beyond that observed with cocaine alone. In adults, eticlopride pretreatment partially attenuated the cocaine-mediated increase in zif268 expression. E20 and P5 D2 receptors appear to be negatively coupled to zif268 expression; whereas the adult D2 receptor, like the D1 receptor, appears to stimulate zif268 expression. Acute cocaine increased D1 but not D2 receptor mRNA levels within 24 h but had no effect on D1 or D2 receptor binding. By late embryonic development, some striatal neurons possess DA receptors coupled to IEG (zif268) activation. Postnatally, D1 receptor activation consistently increases zif268 transcription, but the coupling of D2 receptors to zif268 changes from decidedly negative at an early postnatal age to slightly positive in adults. These results are consistent with a role for DA in regulating striatal neuronal differentiation and development.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"121-32"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00034-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19804083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A1-adenosine receptor gene expression in fetal rat brain.","authors":"D R Weaver","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adenosine influences neurotransmitter release, neuronal excitability, and firing rate, through A1-adenosine receptors (A1-R). Caffeine and related methylxanthines are adenosine receptor antagonists. Exposure of developing rodents to caffeine is associated with subtle, long-term changes in neurochemistry and behavior. The developmental appearance of A1-R gene expression was examined in rats by in situ hybridization. On gestational day (GD) 10, A1-R mRNA was expressed at very high levels in placental mesometrium. Expression of A1-R mRNA in brain was first detected on GD 14. Hybridization was restricted to portions of neuroepithelium, caudate-putamen, piriform cortex, hypoglossal nucleus, and ventral horn of spinal cord. Neuroepithelial A1-R mRNA increased in intensity and distribution at subsequent ages, reaching a maximum on GD 20 (the latest age studied). Hybridization signal was detected, with regional variation in intensity, throughout much of the brain by GD 16, with additional increases in extent and intensity through GD 20. Generally, a caudal > rostral gradient of hybridization intensity was apparent. The distribution on GD 20 resembled the widespread yet heterogeneous pattern observed in the adult, with high levels of A1-R gene expression in cortex, hippocampus, thalamus, cerebellum, pontine nuclei, brainstem motor nuclei, and spinal cord. Northern blot analysis confirmed the age-related increase in abundance of A1-R transcripts (ca. 3.5 and 5.5 kb). The early and widespread expression of A1-R mRNA, coupled with previous reports of prenatal A1-R binding, suggests that adenosine and adenosine antagonists, including caffeine, may influence neuronal differentiation, migration or synaptogenesis, thus producing long-lasting effects on brain and behavior.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"205-23"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19805161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Demotes-Mainard, C Henry, Y Jeantet, J Arsaut, E Arnauld
{"title":"Postnatal ontogeny of dopamine D3 receptors in the mouse brain: autoradiographic evidence for a transient cortical expression.","authors":"J Demotes-Mainard, C Henry, Y Jeantet, J Arsaut, E Arnauld","doi":"10.1016/0165-3806(96)00041-7","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00041-7","url":null,"abstract":"<p><p>The expression of dopamine D3 receptors is relatively low in the adult brain and is mainly restricted to the limbic region. We studied here the postnatal development of these receptors in the mouse brain by quantitative autoradiography using [3H](+/-)-7-OH-DPAT as ligand. In all brain regions examined, there was a progressive increase in D3 receptor protein expression from birth to the weaning period, a pattern reminiscent of that of dopamine D2 rather than D1 receptors. In broad outline, the regional distribution of D3 receptors during brain ontogeny resembled that observed in adult animals, the labelling being detected earlier in the structures with the higher density in the adult. The highest and earliest expression of D3 receptors was observed in the islands of Calleja and olfactory tubercle, where [3H]7-OH-DPAT binding was already present at birth. D3 receptors appeared at postnatal day 4 in the nucleus accumbens, at postnatal day 8 in the substantia nigra, in the medial mamillary nucleus and in the anterior thalamic complex, and at postnatal day 11 in the archaeocerebellum. In contrast to other brain structures where the developmental pattern of D3 receptor expression parallelled its distribution and density in the adult brain, there was a transient cortical expression of [3H]7-OH-DPAT binding between postnatal days 6 and 15, confined to a longitudinal strip in the dorso-lateral part of the parietal cortex. This expression had disappeared by postnatal day 21 and was not detected in adult mice. These developmental findings, and particularly the transient cortical expression of functional receptors, point to the involvement of D3 receptors in ontogenic processes.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"166-74"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0165-3806(96)00041-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19804088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C O Arnaiz, L L Taylor, D J Stehouwer, C van Hartesveldt
{"title":"An aromatic L-amino acid decarboxylase inhibitor blocks L-dopa-induced air-stepping in neonatal rats.","authors":"C O Arnaiz, L L Taylor, D J Stehouwer, C van Hartesveldt","doi":"10.1016/0165-3806(96)00018-1","DOIUrl":"https://doi.org/10.1016/0165-3806(96)00018-1","url":null,"abstract":"<p><p>Rat pups suspended in air and administered L-DOPA engage in a locomotor behavior termed air-stepping. The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats. NSD 1015 dose-dependently increased the latency to onset and decreased the duration of L-DOPA-induced air-stepping. Thus L-DOPA induces air-stepping only after its conversion to dopamine and/or noradrenaline.</p>","PeriodicalId":9057,"journal":{"name":"Brain research. Developmental brain research","volume":"94 2","pages":"234-7"},"PeriodicalIF":0.0,"publicationDate":"1996-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19805163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}