Evidence for subdivisions in the human suprachiasmatic nucleus

The human suprachiasmatic nucleus was analysed by immunohistochemical demonstration of various substances in combination with 3-dimensional computerized reconstruction and video overlay facilities. In the human, the suprachiasmatic nucleus is not as compact as in the rodent. Its boundaries are not easily delineated using conventional stains, and it shows no obvious cytoarchitectonic structure. However, based on its chemoarchitecture, the human suprachiasmatic nucleus can be apportioned into five major subdivisions: Dorsal, comprising a crescent shaped mass of densely packed neurophysin/vasopressin-neurons as well as neurotensin-neurons, and also containing 3-fucosyl-N-acetyl-lactosamine (FAL)-positive neurons in its medial part. Central, occupying the core of the nucleus and consisting precisely of a region devoid of neurophysin/vasopressin neurons but demarcated by calbindin, synaptophysin, and a circumscribed cluster of vasoactive intestinal polypeptide-neurons and containing neurotensin neurons as well. Anteroventrally this division also contains some intermingled neurons positive for neurotensin, neuropeptide Y, somatostatin, and FAL. Ventral, extending from the anterior extreme of the preoptic recess caudolaterally to a field between the optic chiasm and the anteroventral margin of the supraoptic nucleus. This subdivision is specified by synaptophysin, calbindin, and substance P immunoreactivity and is almost free of glial fibrillary acidic protein. From its rostral portion, fibers immunoreactive for calbindin, vasoactive intestinal polypeptide, synaptophysin, and substance P protrude deeply into the optic chiasm. Medial, comprising a thin band between the subependymal zone and the dorsal subdivision, containing scattered somatostatin neurons. External, extending as a band around the dorsal and lateral borders of the nucleus, containing astrocytes expressing the FAL-epitope and scattered neurophysin/vasopressin and neurotensin neurons. These findings indicate that the human suprachiasmatic nucleus contains well-defined subdivisions with different, chemically specific, connections and provides a basis for comparing these subdivisions with the structure and function of subdivisions previously described for the suprachiasmatic nucleus in experimental animals. In addition, the findings strengthen the concept that the human suprachiasmatic nucleus generates and expresses circadian rhythms in a manner similar to that documented for the suprachiasmatic nucleus in experimental animals, and suggest that different subdivisions may subserve specific functional roles.     

Close microtopographical relationships between sympathetic nerve terminals and bulbous process endings of pinealocytes in the pineal gland of the Mongolian gerbil

Abstract: Previous studies have shown that pinealocytes of the gerbil pineal gland exhibit processes that form terminal swellings filled with abundant electron-lucent microvesicles. The membrane of these presumptive secretory microvesicles is known to contain synaptophysin, a major integral glycoprotein of neuronal synaptic vesicles. The present study was conducted to evaluate the microtopographical relationships between the vesicle-rich process swellings and intra-pineal nerve terminals. For this purpose, both nerve terminals and pinealocyte process endings were visualized immunohistochemically in the same semi-thin sections of plastic-embedded gerbil pineals, using antibodies directed against synaptophysin. This approach consistently revealed close spatial associations of punctate immunopositive nerve endings with intensely stained bulbous process terminals of pinealocytes in or near the perivascular spaces. The light-microscopic observations of intimate neuronal-pinealocytic relationships were corroborated at the electron-microscopic level. Perivascular varicosities with ultrastructural features characteristic of sympathetic nerve terminals were frequently juxtaposed to vesicle-filled process endings of pinealocytes. Analysis of serial thin sections showed that multiple point-to-point contacts are encountered between noradrenergic nerve terminals and pinealocytic process swellings. Our morphological findings imply that bulbous process terminals, at least in the gerbil pineal gland, are major targets for the neuronal control of the secretory activity of pinealocytes.     

Desmoplastic cerebral astrocytoma of infancy intermingling with atypical glial cells

Despite the rarity of desmoplastic cerebral astrocytoma of infancy (DCAI), it has distinct clinical and pathological features. The present case is a typical DCAI except for its detection and operational age and intermingling with pleomorphic glial cells. In this case, although a cystic lesion of the right temporal lobe was noticed when the patient was 6 months old, it was not regarded as a tumor and wasn't removed until he was 9 years old. It is quite unusual that a DCAI was able to exist in the cerebrum for 9 years. However, no metastasis occurred and distinct macroscopic and microscopic features of the tumor were not different from typical DCAI except for an intermingling with pleomorphic glial cells. Furthermore, even in the pleomorphic areas, the absence of necrosis and an MIB-1 index of 2.9% indicated non-aggressive growth. These features of the present case may provide additional information as to the character of DCAI, which generally has a favorable prognosis.     

Synaptophysin Expression in Rat Retina Following Acute High Intraocular Pressure

In response to injury, synapse alteration may occur earlier than the changes in the cell body of neurons. Although retinal ganglion cell death and thinning of the inner part of retina were found after acute high intraocular pressure (HIOP), the structural and functional changes of synapses in the retina remain unknown. In the present study, we investigated the protein and mRNA expression of synaptophysin (SYN), an important molecule closely related to synaptic activities, synaptogenesis and synaptic plasticity. In addition, we also studied the ultrastructural changes of the retinal synapses. We found that (1) synaptophysin was upregulated transiently at both protein and mRNA level following HIOP; (2) broadened distribution of synaptophysin protein was present within the outer nuclear layer at the early stage following HIOP; (3) in the outer nuclear layer bouton-like vesicle-containing structures were observed by electron microscopy. This data suggested that, besides degeneration, synapses in rat retina may undergo regenerative events following HIOP.     

神经生长因子对痴呆模型鼠海马突触素的影响

切断SD老年鼠(24月龄)左侧穹窿海马伞.造成隔海马胆碱能系统损害的痴呆模型. 用免疫组化和图像分析技术分析神经生长因子对痴呆鼠海马突触素的影响.实验证明损伤一个月后.损伤对照组损伤侧海马CAI区多形层、辐射层、腔隙分子层和齿状回分子层突触素含量分别是减少了28.17% 、32.15%、17.36%和35.22%:NGF治疗组、损伤侧海马CAI区多形层、辐射层、腔隙分子层和齿状回分子层突触素含量只减少了6.17%、5.52%、13.50%和3.81%.提示神经生长因子能够促使痴呆鼠海马内突触素含量的增多.     

Central Neurocytoma: 2 Case Reports and Review of the Literature

Summary  Central neurocytoma is a rare benign tumor of the central nervous system occuring in young adults and typically located in the ventricles. The tumor is composed of small round cells with neuronal differentiation and has a favourable prognosis. We report two cases of giant central neurocytomas with a triventricular extension in two young women.  The first case concerned a 26 years old righthanded woman in whom an intraventricular mass was discovered, after a car accident with head trauma. Skull radiography showed an enlargment of the sella turcica. A CT scan performed in order to examine the pituitary gland revealed a voluminous and heterogenous intraventricular tumor with calcification.  The second case concerned a 26 years old righthanded woman, presenting with a 4 Glasgow Coma Scale Score preceded by an acute onset of headache with projectile vomiting. A CT scan performed in emergency revealed a voluminous intraventricular mass with significant hydrocephalus.  We review the different pathological and topographical patterns of previously published neurocytomas and discuss surgical management, effectiveness of radiation therapy and biological behavior.     

Vascular dementia in Spatz-Lindenberg's disease (SLD): cortical synaptophysin immunoreactivity as compared with dementia of Alzheimer type and non-demented controls

Summary The generalized form of von Winiwarter-Buerger's disease (WBD) occasionally involves the brain. However, pure cerebral forms of the disease were also described by Spatz and Lindenberg (Spatz-Lindenberg's disease, SLD). Both, the type I, which involves the large basal arteries, and the type II, which results in a sickle-shaped granular atrophy of the cerebral cortex, are often accompanied by (vascular) dementia, which Lindenberg and Spatz mainly attributed to the bilateral involvement of the second frontal gyrus by granular atrophy. Recently, synaptic deprivation of the cortical gray matter has been shown to occur in the dementia of Alzheimer type (DAT) and other neurodegenerative disorders. In DAT, the synaptic loss highly correlated with the degree of the mental impairment. We wanted to examine whether similar changes also occurred in dementia of vascular origin, for which SLD, although infrequent, is a typical example. In fact, we found that in three cases of typical SLD type II the synaptophysin immunoreactivity of the cortical neuropil in areas without overt infarcts or scar formation was as much reduced as in Alzheimer's disease. Although it must be taken into account that in the present cases the synapse loss might, at least in part, be due to secondary (Wallerian) degeneration as a result of the neuronal loss in the watershed regions of the arterial blood supply, it cannot be excluded that a decline of cortical synaptic contacts in areas without necroses or scars may occur as a primary event, contributing to the pathogenesis of the dementia. Final conclusions can only be expected from investigations into further cases of cerebro-vascular disorders with and without dementia.Presented at the 37th Annual Meeting of the German Society of Neuropathology and Neuroanatomy, e. V., Hamburg, September 23–26, 1992     

Effect of Panaxtriol Saponins on synaptophysin and postsynaptic density-95 expression at different periods of cerebral infarction*☆

BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Chinese medicinal substances may play an important role in the expression of Syp and PSD-95. OBJECTIVE： To observe the effect of Panaxtriol Saponins （PTS）, an active component in Sanqi tongshu capsules, on the expression of Syp and PSD-95 after cerebral infarction at different time points in rats, so as to examine the cerebral function remodeling mechanism. DESIGN, TIME AND SETTING： A randomized and controlled observation which was performed in Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine from January to March, 2007. MATERIALS： Twenty-six healthy male Sprague Dawley rats were used to establish middle cerebral artery occlusion based on the Longa method. Sanqi tongshu capsules （containing 100 mg PTS per tablet） were provided by the Chengdu Huashen Group and nimodipine tablets （30 mg） by Tianjin Zhongyang Pharmaceutical Co., Ltd. METHODS： Twenty-six rats were randomly divided into an operation group （n = 21 ） and a control group （n = 5）. The operation group underwent the EZ Longa procedure to make the middle cerebral artery occlusion model. After surgery rats were randomly divided into a model group, a PTS group and a nimodipine group, with seven rats in each group. Rats were intragastrically administrated with saline （2 mL/d） in the model group, with Sanqi tongshu capsule （5.4 mg/100 g/d） in the PTS group, and with nimodipine （1.73 mg/100 g/d） in the nimodipine group. Rats in the control group did not undergo model establishment and drug administration. MAIN OUTCOME MEASURES： The expressions of Syp and PSD-95 were measured by immunohistochemical and image analysis at days 3, 7 and 28 after the operation. RESULTS： The expression of Syp and PSD-95 in the operation group was significantly lower than in the control group at days 3, 7     

Effects of genistein and 17 beta-estradiol on hippocampal synaptophysin expression in ovariectomized rats

BACKGROUND:Phytoestrogen,derived from plants,is an estrogen-like element,and is effective and safe for estrogen replacement.OBJECTIVE:To compare the interventional effects of genistein and 17 β-estradiol on learning and memory and synaptophysin(SYN)expression in the hippocampus of ovariectomized rats.DESIGN:Randomized controlled animal study.SETTING:Department of Neurology,the Third Affiliated Hospital,Xiangya Medical College,Central South University. MATERIALS:130 healthy female Sprague Dawley(SD)rats,6 months old and weighing(293.1±10.2)g,were provided by the Second Xiangya Hospital of Central South University.This animal experiment received confirmed consent from the local ethics committee.All rats were randomly divided into 5 groups,including baseline group(n＝10),sham operation group(n＝30),ovariectomlzed group(n＝30),genistein group(n＝ 30),and 17 β-estradiol group(n＝30).Rats in the latter four groups were observed for 3 weeks(n＝10)and for 15 weeks(n＝20)after model establishment.METHODS:This study was performed at the Department of Endocrinology,the Second Affiliated Hospital,Xiangya Medical College,Central South University from August 2005 to January 2006.Animals were not submitted to any treatment in the baseline group,but anesthetized and sacrificed at the 7 months of age.After anesthesia in the ovariectomized,genistein,and 17 β-estradiol groups,both ovaries were separated and resected to establish an ovariectomized model.The same volume of fat was resected in the sham operation group.After surgery,rats were intraperitoneally injected with 5 mg/kg genistein in the genistein group,10 μ g/kg 17 β-estradiol in the 17 β-estradiol group,and 0.1 mL/100 g dimethyl sulfoxide (DMSO)/polyethylene glycol(PEG)-200 stock solution in the sham peration and ovariectomized groups once a day until one day before sacrifice.MAIN OUTCOME MEASURES:①Learning and memory changes of SD rats were detected using water maze behavioral testing 3 and 15 weeks after surgery.②SYN expression in the hippocampus was measured using immunohistochemistry. RESULTS:A total of 16 out of 130 rats died due to infection,and 114 rats were included in the final analysis.①Comparison of water maze results from the five groups:by 3 and 15 weeks after surgery, escape latency was prolonged and platform-crossing times decreased in the ovariectomized group compared to the baseline,genistein,17 β-estradiol,and sham operation groups(t＝4.17--14.64,P＜0.05).However, there were no significant differences in escape latency and platform-crossing times among the sham operation,genistein,and 17 β-estradiol groups(P＜0.05).②Distribution and quantity of SYN immunoreactive products in hippocampus:SYN-immunoreactive cells stained darkly in the baseline and sham operation groups,but were lightly stained in the genistein,17 β-estradiol,and ovariectomized groups.In particular,SYN-immunoreactive cells stained lightly in the ovariectomized group 15 weeks after surgery. SYN correction gray values in hippocampal sub-regions,especially in the mossy fiber layer of the CA3 region,of the ovariectomized group was lower compared to the baseline,sham operation,17 β-estradiol,and genistein groups(t＝12.57-23.92,P＜0.05)15 weeks after surgery.However,there were no significant differences in SYN correction gray values among the baseline,sham operation,17 β-estradiol and genistein groups(P＜0.05).CONCLUSION:Genistein or 17 β-estradiol supplemental therapy antagonizes memory deterioration,due to endogenous estrogen deficiency and blocks the decrease of SYN expression in the hippocampus.The effect of genistein is similar to 17 β-estradiol.     

NSCs promote hippocampal neurogenesis,metabolic changes and synaptogenesis in APP/PS1 transgenic mice

Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12‐month‐old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H‐MRS). The results showed that N‐acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg‐NSC mice compared with the Tg‐PBS and Tg‐AD mice 10 weeks after NSCs transplantation. NSC‐induced an increase in expression of synaptophysin and postsynaptic protein‐95, and the number of neurons with normal synapses was significantly increased in Tg‐NSC mice. More doublecortin‐, BrdU/NeuN‐ and Nestin‐positive neurons were observed in the hippocampal DG and SVZ of the Tg‐NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H‐MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H‐MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.