Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22–25 weeks, we examined site- and stage-dependent differences in CD68-positive microglial cell distribution in human fetal brains. CD68 positive cells were evident in the floor of the fourth ventricle and the pons and olive at 15-16 weeks, accumulating in and around the hippocampus at 22–25 weeks. At both stages, the accumulation of these cells was evident around the optic tract and the anterior limb of the internal capsule. When we compared CD68-positive cell distribution with the topographical anatomy of GAP43-positive developing axons, we found that positive axons were usually unaccompanied by CD68-positive cells, except in the transpontine corticofugal tract and the anterior limb of the internal capsule. Likewise, microglial cell distribution did not correspond with habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses.
Carbonic anhydrase type IX (CA9) is known to express in the fetal joint cartilage to maintain pH against hypoxia. Using paraffin-embedded histology of 10 human fetuses at 10-16 weeks of gestation with an aid of immunohistochemistry of the intermediate filaments, matrix components (collagen types I and II, aggrecan, versican, fibronectin, tenascin, and hyaluronan) and CA9, we observed all joints and most of the entheses in the body. At any stages examined, CA9-poisitive cells were seen in the intervertebral disk and all joint cartilages including those of the facet joint of the vertebral column, but the accumulation area was reduced in the larger specimens. Glial fibrillary acidic protein (GFAP), one of the intermediate filaments, expressed in a part of the CA9-positive cartilages. Developing elastic cartilages were positive both of CA9 and GFAP. Notably, parts of the tendon or ligament facing to the joint, such as the joint surface of the annular ligament of the radius, were also positive for CA9. A distribution of each matrix components examined was not same as CA9. The bone-tendon and bone-ligament interface expressed CA9, but the duration at a site was limited to 3-4 weeks because the positive site was changed between stages. Thus, in the fetal entheses, CA9 expression displayed highly stage-dependent and site-dependent manners. CA9 in the fetal entheses seemed to play an additional role, but it was most likely to be useful as an excellent marker of mechanical stress at the start of enthesis development.
Carbonic anhydrase type IX; Intermediate filaments; Joints; Enthesis; Human fetus
Using immunohistochemical staining for alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.
Salivary glands; Myoepithelial cells; Immunohistochemistry; Adult; Fetus
We examined pharyngeal nerve courses in paraffin-embedded sagittal sections from 10 human fetuses, at 25-35 weeks of gestation, by using S100 protein immunohistochemical analysis. After diverging from the glossopharyngeal and vagus nerves at the level of the hyoid bone, the pharyngeal nerves entered the constrictor pharyngis medius muscle, then turned upward and ran superiorly and medially through the constrictor pharyngis superior muscle, to reach either the levator veli palatini muscle or the palatopharyngeus muscle. None of the nerves showed a tendency to run along the posterior surface of the pharyngeal muscles. Therefore, the pharyngeal nerve plexus in adults may become established by exposure of the fetal intramuscular nerves to the posterior aspect of the pharyngeal wall because of muscle degeneration and the subsequent rearrangement of the topographical relationship between the muscles that occurs after birth.
Pharyngeal nerve plexus; Glossopharyngeal nerve; Constrictor pharyngis superior muscle; Levator veli palatini muscle; Human fetus
The supinator muscle originates from the annular ligament of the radius, and the muscle fibers and ligament take a similar winding course. Likewise, the coccygeus muscle and the sacrospinous ligament are attached together, and show a similar fiber orientation. During dissection of adult cadavers for our educational curriculum, we had the impression that these ligaments grow in combination with degeneration of parts of the muscles. In histological sections of 25 human fetuses at 10-32 weeks of gestation, we found that the proximal parts of the supinator muscle were embedded in collagenous tissue when the developing annular ligament of the radius joined the thick intermuscular connecting band extending between the extensor carpi radialis and anconeus muscles at 18-22 weeks of gestation, and the anterior parts of the coccygeus muscle were surrounded by collagenous tissue when the intramuscular tendon became the sacrospinous ligament at 28-32 weeks. Parts of these two muscles each seemed to provide a mold for the ligament, and finally became involved with it. This may be the first report to indicate that a growing ligament has potential to injure parts of the "mother muscle," and that this process may be involved in the initial development of the ligament.
Supinator muscle; Coccygeus muscle; Sacrospinous ligament; Annular ligament of the radius; Human fetus
It is still unclear whether the longitudinal anal muscles or conjoint longitudinal coats (CLCs) are attached to the vagina, although such an attachment, if present, would appear to make an important contribution to the integrated supportive system of the female pelvic floor.
Materials and Methods
Using immunohistochemistry for smooth muscle actin, we examined semiserial frontal sections of 1) eleven female late-stage fetuses at 28-37 weeks of gestation, 2) two female middle-stage fetus (2 specimens at 13 weeks), and, 3) six male fetuses at 12 and 37 weeks as a comparison of the morphology.
In late-stage female fetuses, the CLCs consistently (11/11) extended into the subcutaneous tissue along the vaginal vestibule on the anterior side of the external anal sphincter. Lateral to the CLCs, the external anal sphincter also extended anteriorly toward the vaginal side walls. The anterior part of the CLCs originated from the perimysium of the levator ani muscle without any contribution of the rectal longitudinal muscle layer. However, in 2 female middle-stage fetuses, smooth muscles along the vestibulum extended superiorly toward the levetor ani sling. In male fetuses, the CLCs were separated from another subcutaneous smooth muscle along the scrotal raphe (posterior parts of the dartos layer) by fatty tissue.
In terms of topographical anatomy, the female anterior CLCs are likely to correspond to the lateral extension of the perineal body (a bulky subcutaneous smooth muscle mass present in adult women), supporting the vaginal vestibule by transmission of force from the levator ani.
Anal canal; levator ani muscle; longitudinal anal muscle; rectum; smooth muscle; embryology
There is little or no information about the distribution of elastic fibers in the human fetal head. We examined this issue in 15 late-stage fetuses (crown-rump length, 220-320 mm) using aldehyde-fuchsin and elastica-Masson staining, and we used the arterial wall elastic laminae and external ear cartilages as positive staining controls. The posterior pharyngeal wall, as well as the ligaments connecting the laryngeal cartilages, contained abundant elastic fibers. In contrast with the sphenomandibular ligament and the temporomandibular joint disk, in which elastic fibers were partly present, the discomalleolar ligament and the fascial structures around the pterygoid muscles did not have any elastic fibers. In addition, the posterior marginal fascia of the prestyloid space did contain such fibers. Notably, in the middle ear, elastic fibers accumulated along the tendons of the tensor tympani and stapedius muscles and in the joint capsules of the ear ossicle articulations. Elastic fibers were not seen in any other muscle tendons or vertebral facet capsules in the head and neck. Despite being composed of smooth muscle, the orbitalis muscle did not contain any elastic fibers. The elastic fibers in the sphenomandibular ligament seemed to correspond to an intermediate step of development between Meckel's cartilage and the final ligament. Overall, there seemed to be a mini-version of elastic fiber distribution compared to that in adults and a different specific developmental pattern of connective tissues. The latter morphology might be a result of an adaptation to hypoxic conditions during development.
Elastic fibers; Sphenomandibular ligament; Ear ossicles; Head; Human fetus
We examined a series of changes that occur in the trabecular meshwork fibers of human eyes during fetal development at 12-30 weeks of gestation. At 12 and 15 weeks, the uveal meshwork was stained black with silver impregnation (indicating the predominance of collagen types III and IV) in the endomysium of the ciliary muscle. At 20 weeks, in combination with Schlemm's canal, a dense fibrous tissue mass corresponding to the trabecular meshwork anlage appeared and was colored black. The anlage was continuous with the corneal endothelium rather than with the ciliary muscle. Until 25 weeks, the trabecular meshwork was identifiable as fragmented fiber bundles that stained red-black, suggesting a mixture of collagen types I, III, and IV. At 30 weeks, half of the ciliary muscle fibers were inserted into the scleral spur and not into the meshwork. Therefore, any contribution of ciliary muscle contraction to the differentiation of the trabecular meshwork would appear to be limited. We hypothesize that an uneven distribution of mechanical stresses in the area of the cornea-sclera junction causes a tear thereby creating Schlemm's canal and is accompanied by a change in the collagen fiber types comprising the meshwork.
Trabecular meshwork; Schlemm's canal; Collagen; Silver staining
Connexin-43, a major gap junction protein, and cytokeratin-19, one of the intermediate filament keratins, are known to be markers of well-differentiated epithelium. In this study, we investigated the expression of these markers in the head region, lungs, and abdominal organs of 10 human mid-term fetuses. The expression of connexin-43 was found to be restricted to the dura mater, kidney, and adrenal cortex. In the kidney, we found a clear site-dependent difference in the expression pattern of these markers: connexin-43 expression was observed in the tubules of the renal cortex whereas cytokeratin-19 was strongly expressed in the collecting ducts and renal pelvis. This difference remained unchanged throughout the fetal stages examined. Immunoreactivity was not observed for either of the markers in the intrarenal vessels, including the glomeruli, and mesangial cells. Connexin-43 expression seemed to be restricted to the metanephric vesicle-derived structures that differentiate in the urogenital ridge of the splanchnic mesoderm. The adrenal cortex also originates from the same para-aortic mesoderm. In contrast, in the urogenital organs, cytokeratin-19 seemed to be expressed in ducts derived from the urogenital sinus.
Connexin-43; Cytokeratin-19; Kidney; Immunohistochemistry; Human fetus
Synaptic plasticity of the female hippocampus may cyclically fluctuate across the estrous cycle. The spine density fluctuation had been explained by fluctuation of plasma estradiol (E2) and progesterone (PROG), with the assumption that these steroids penetrate into the hippocampus. Recently, however, we demonstrated that male hippocampal levels of sex steroids are much higher than those in plasma, suggesting a weak contribution of plasma steroids to the spine density. By combination of mass-spectrometric analysis with HPLC-purification and picolinoyl-derivatization of hippocampal sex steroids, we determined the accurate concentration of E2 and PROG at four stages of plasma estrous cycle including Proestrus (Pro), Estrus (Est), Diestrus 1 (D1), and Diestrus 2 (D2). Hippocampal levels of E2 and PROG showed cyclic fluctuation with a peak at Pro for E2 and at D1 for PROG, having a positive correlation with the plasma estrous cycle. All these sex steroid levels are much higher in the hippocampus than in plasma. Even after ovariectomy a significant levels of E2 and PROG were observed in the hippocampus. The total spine density showed higher values at Pro and D1, and lower values at Est and D2, having a good correlation with the peak levels of hippocampal E2 or PROG. We also examined fluctuation of the head diameter of spines. Interestingly, mRNA expression level of steroidogenic enzymes (P450arom and 17β-HSD, etc.) and sex-steroid receptors did not significantly change across the estrous cycle. Therefore, the fluctuation of total hippocampal PROG (equal to sum of hippocampus-synthesized PROG and plasma PROG) may be originated from the contribution of cyclic change in plasma PROG, which can induce the fluctuation of total hippocampal E2, since steroid conversion activity of hippocampus might be nearly the same across the estrus cycle.
hippocampus-synthesized steroids; estradiol; dendritic spines; estrous cycle; progesterone
Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100–1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
corticosterone; hippocampus; kinase; thorn; stress; spine
In the developing human musculoskeletal system, cell death with macrophage accumulation occurs in the thigh muscle and interdigital area. To comprehensively clarify the distribution of macrophages, we immunohistochemically examined 16 pairs of upper and lower extremities without the hip joint (left and right sides) obtained from 8 human fetuses at approximately 10-15 weeks of gestation. Rather than in muscles, CD68-positive macrophages were densely distributed in loose connective tissues of the flexor aspects of the extremities, especially in the wrist, hand and foot. In contrast, no or fewer macrophages were evident in the shoulder and the extensor aspects of the extremities. The macrophages were not concentrated at the enthesis of the tendon and ligament, but tended to be arranged along other connective tissue fibers. Deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling revealed apoptosis in the hand lumbricalis muscles, but not in the area of macrophage accumulation. Likewise, podoplanin-positive lymphatic vessels were not localized to areas of macrophage accumulation. Re-organization of the connective tissue along and around the flexor tendons of the hand and foot, such as development of the bursa or tendon sheath at 10-15 weeks, might require the phagocytotic function of macrophages, although details of the mechanism remain unknown.
CD68-positive macrophages; Hand and foot; Lymphatic vessels; Enthesis; Human fetus
Although the rectus abdominis and its sheath are well known structures, their development in the human fetus is poorly understood.
Materials and Methods
We examined rectus abdominis and sheath development in semiserial horizontal sections of 18 fetuses at 5-9 weeks of gestation.
Rectus muscle differentiation was found to commence above the umbilicus at 6 weeks and extend inferiorly. Until closure of the anterior chest wall via fusion of the bilateral sternal anlagen (at 7 weeks), the anterior rectal sheath originated from the external oblique and developed towards the medial margin of the rectus abdominis at all levels, including the supracostal part. After formation of the anterior sheath, fascial laminae from the internal oblique and transversus abdominis contributed to formation of the posterior rectus sheath. However, the posterior sheath was absent along the supracostal part of the rectus abdominis, as the transversus muscle fibers reached the sternum or the midline area. Therefore, it appeared that resolution of the physiological umbilical hernia (8-9 weeks) as well as chest wall closure was not required for development of the rectus abdominis and its sheath. Conversely, in the inferior part of the two largest fetal specimens, after resolution of the hernia, the posterior sheath underwent secondary disappearance, possibly due to changes in mechanical stress.
Upward extension of the rectus abdominis suddenly stopped at the margin of the inferiorly developing pectoralis major without facing the external intercostalis. The rectus thoracis, if present, might correspond to the pectoralis.
Rectus abdominis; rectus sheath; pectoralis; sternalis; sternum; rib
Fetal development of the cartilage of the pharyngotympanic tube (PTT) is characterized by its late start. We examined semiserial histological sections of 20 human fetuses at 14-18 weeks of gestation. As controls, we also observed sections of 5 large fetuses at around 30 weeks. At and around 14 weeks, the tubal cartilage first appeared in the posterior side of the pharyngeal opening of the PTT. The levator veli palatini muscle used a mucosal fold containing the initial cartilage for its downward path to the palate. Moreover, the cartilage is a limited hard attachment for the muscle. Therefore, the PTT and its cartilage seemed to play a critical role in early development of levator veli muscle. In contrast, the cartilage developed so that it extended laterally, along a fascia-like structure that connected with the tensor tympani muscle. This muscle appeared to exert mechanical stress on the initial cartilage. The internal carotid artery was exposed to a loose tissue facing the tubal cartilage. In large fetuses, this loose tissue was occupied by an inferior extension of the temporal bone to cover the artery. This later-developing anterior wall of the carotid canal provided the final bony origin of the levator veli palatini muscle. The tubal cartilage seemed to determine the anterior and inferior margins of the canal. Consequently, the tubal cartilage development seemed to be accelerated by a surrounding muscle, and conversely, the cartilage was likely to determine the other muscular and bony structures.
Pharyngotympanic tube cartilage; Levator veli palatini muscle; Internal carotid artery; Tensor tympani muscle; Human fetuses
We recently demonstrated the morphology of the anococcygeal ligament. As the anococcygeal ligament and raphe are often confused, the concept of the anococcygeal raphe needs to be re-examined from the perspective of fetal development, as well as in terms of adult morphology.
Materials and Methods
We examined the horizontal sections of 15 fetuses as well as adult histology. From cadavers, we obtained an almost cubic tissue mass containing the dorsal wall of the anorectum, the coccyx and the covering skin. Most sections were stained with hematoxylin and eosin or Masson-trichrome solution.
The adult ligament contained both smooth and striated muscle fibers. A similar band-like structure was seen in fetuses, containing: 1) smooth muscle fibers originating from the longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the external anal sphincter (EAS). However, in fetuses, the levator ani muscle did not attach to either the band or the coccyx. Along and around the anococcygeal ligament, we did not find any aponeurotic tissue with transversely oriented fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous tissue mass was located at a gap between bilateral levator ani slings; this site corresponded to the dorsal side of the ligament and the EAS in the immediately deep side of the natal skin cleft.
We hypothesize that a classically described raphe corresponds to the specific subcutaneous tissue on the superficial or dorsal side of the anococcygeal ligament.
Anal canal; rectum; smooth muscle; embryology; anatomy; histology
To investigate why the development of a completely circular striated sphincter is so rare, we examined histological sections of 11 female and 11 male mid-term human fetuses. In male fetuses, the striated muscle initially extended in the frontal, rather than in the horizontal plane. However, a knee-like portion was absent in the female fetal urethra because, on the inferior side of the vaginal end, a wide groove for the future vestibule opened inferiorly. Accordingly, it was difficult for the developing striated muscle to surround the groove, even though there was not a great difference in width or thickness between the female vestibule and the male urethra. The development of a completely circular striated sphincter seems to be impossible in females because of interruption of the frontal plane by the groove-like vestibule. However, we cannot rule out the possibility that before descent of the vagina, the urethral striated muscle extends posteriorly.
Urethal rhabdosphincter; Genital tract; Urogenital sinus; Colliculus; Human fetus
Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus.
Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100–1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2–0.4 µm) was increased even at low CORT levels (100–200 nM). The density of middle-head spines (0.4–0.5 µm) was increased at high CORT levels between 400–1000 nM. The density of large-head spines (0.5–1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect.
These results imply that stress levels of CORT (100–1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways.
Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21).
The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of 3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h.
These results imply the complete pathway of corticosteroid synthesis of ‘pregnenolone →PROG→DOC→CORT’ in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.
Computer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply.
Tissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas.
The immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas.
This observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.
Gastroduodenal artery; Dorsal pancreas; Pancreatic polypeptide immunohistochemistry; Human fetus
Accurate 3D determination of postsynaptic structures is essential to our understanding memory-related function and pathology in neurons. However, current methods of spine analysis require time-consuming and labor-intensive manual spine identification in large image data sets. Therefore, a realistic implementation of algorithm is necessary to replace manual identification. Here, we describe a new method for the automated detection of spines and dendrites based on analysis of geometrical features. Our “Spiso-3D” software carries out automated dendrite reconstruction and spine detection using both eigenvalue images and information of brightness, avoiding detection of pseudo-spines. To demonstrate the potential application of Spiso-3D automated analysis, we distinguished the rapid effects of androgen and estrogen on rapid modulation of spine head diameter in the hippocampus. These findings advance our understanding of neurotrophic function of brain sex steroids. Our method is expected to be valuable to analyze vast amounts of dendritic spines in neurons in the mammalian cerebral cortex.
automatic detection; hippocampus; steroids; synapse; spine
Sex steroids play essential roles in the modulation of synaptic plasticity and neuroprotection in the hippocampus. Accumulating evidence shows that hippocampal neurons synthesize both estrogen and androgen. Recently, we also revealed the hippocampal synthesis of corticosteroids. The accurate concentrations of these hippocampus-synthesized steroids are determined by liquid chromatography–tandem mass-spectrometry in combination with novel derivatization. The hippocampal levels of 17β-estradiol (E2), testosterone (T), dihydrotestosterone (DHT), and corticosterone (CORT), are 5–15 nM, and these levels are sufficient to modulate synaptic plasticity. Hippocampal E2 modulates memory-related synaptic plasticity not only slowly/genomically but also rapidly/non-genomically. Slow actions of E2 occur via classical nuclear receptors (ERα or ERβ), while rapid E2 actions occur via synapse-localized or extranuclear ERα or ERβ. Nanomolar concentrations of E2 change rapidly the density and morphology of spines in hippocampal neurons. ERα, but not ERβ, drives this enhancement/suppression of spinogenesis in adult animals. Nanomolar concentrations of androgens (T and DHT) and CORT also increase the spine density. Kinase networks are involved downstream of ERα and androgen receptor. Newly developed Spiso-3D mathematical analysis is useful to distinguish these complex effects by sex steroids and kinases. Significant advance has been achieved in investigations of rapid modulation by E2 of the long-term depression or the long-term potentiation.
hippocampus; sex steroid; corticosteroid; estrogen; androgen; synaptic plasticity; spinogenesis
The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head.
Materials and Methods
In human fetuses between 8-30 weeks, we described the topographical anatomy of the vessels, bile duct, duodenum as well as the ventral and dorsal primordia of the pancreatic head with an aid of pancreatic polypeptide immunohisto-chemistry.
The contents of the hepatoduodenal ligament crossed the superior side of the pylorus. Moreover, the right hepatic artery originating from the superior mesenteric artery ran along the superior aspect of the pancreatic head. An arterial arcade, corresponding to the posterior pancreaticoduodenal arteries, encircled the superior part of the pancreatic head, whereas another arcade, corresponding to the anterior pancreaticoduodenal arteries, surrounded the inferior part. The dorsal promordium of the pancreas surrounded and/or mixed the ventral primordium at 13-16 weeks. Thus, both arterial arcades were likely to attach to the dorsal primordium.
The fetal anatomy of the pancreaticoduodenal vascular arcades as well as that of the hepatoduodenal ligament were quite different from adults in topographical relations. Thus, in the stage later than 30 weeks, further rotation of the duodenum along a horizontal axis seemed to be required to move the pylorus posterosuperiorly and to reflect the superior surface of the pancreatic head posteriorly. However, to change the topographical anatomy of the superior and inferior arterial arcades into the final position, re-arrangement of the pancreatic parenchyma might be necessary in the head.
Pancreaticoduodenal arterial arcades; ventral pancreas; pancreatic polypeptide immunohistochemistry; human fetus
Although reports of hypoplasia or absence of the liver of left lobe are not few, descriptions of the intrahepatic vessels are rare but valuable for discussion of the pathogenesis. The present report demonstrates a case of the left surgical lobe hypoplasia that is characterized by 1) the scar-like lobe with few parenchymal tissue and dilated bile ducts, 2) no Spiegel's lobe with the portal vein stuck to the inferior vena cava, 3) unusual configurations of the right hepatic vein and the 8th segmental portal vein branch, 4) the hepatic groove on S8, and 5) the trifurcation pattern of the portal vein primary division. According to the macroscopic and histological observations, we hypothesized that the secondary abnormal peritoneal fusion occurred in utero and/or during the postnatal growth, and that it involved the left portal vein and other adjacent structures, resulting in severe atrophy of the left surgical lobe.