Areas 3a, 3b, and 1 of Human Primary Somatosensory Cortex: 2. Spatial Normalization to Standard Anatomical Space

Interindividual topographical variability of cytoarchitectonically defined somatosensory areas 3a, 3b, and 1 was analyzed in the standard anatomical format of a computerized brain atlas. T1-weighted magnetic resonance images were obtained from 10 postmortem brains. The brains were serially sectioned at 20 μm, sections were stained for cell bodies, and areas 3a, 3b, and 1 were defined with an observer-independent cytoarchitectonic technique. After correction of the sections for deformations due to histological processing, the 3-D reconstructed histological volumes of the individual brains and the volume representations of the cytoarchitectonic areas were adapted to the reference brain of a computerized atlas. Corresponding areas were superimposed in the 3-D space of the reference brain. These population maps describe, for each voxel, how many brains have a representation of one particular cytoarchitectonic area. Each area’s extent is very variable across different brains, but representations of areas 3a, 3b, and 1 in ≥50% of the brains were found in the fundus of the central sulcus, its caudal bank, and on the crown of the postcentral gyrus, respectively. Volumes of interest (VOIs) were defined for each area in which ≥50% of the brains have a representation of that area. Despite close spatial relationship of areas 3a, 3b, and 1 in the postcentral gyrus, the three VOIs overlap by <1% of their volumes. Functional imaging data can now be brought into the same standard anatomical format, and changes in regional cerebral blood flow can be calculated in VOIs of areas 3a, 3b, and 1, which are derived from genuine cytoarchitectonic data.     

Altered neuropeptide concentrations in spontaneously hypertensive rats: cause or consequence?

Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it. We have measured brain concentrations of beta-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. beta-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, mid-brain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord. beta-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.     

In vivo and in vitro visualization of gene expression dynamics over extensive areas of the brain

In vivo monitoring of gene expression using promoter-destabilized fluorescence protein constructs is a powerful method for examining the expression dynamics of immediate-early genes in the brain. However, weak fluorescence signals derived from such constructs have hampered analyses of gene expression over extensive areas of the brain. We succeeded in producing transgenic mice with brains exhibiting high level expression of the reporter gene driven by the Arc gene promoter, which is activated in association with various brain functions (reporter mRNA abundance was near 100-fold greater than endogenous Arc mRNAs). This high expression of the reporter gene enabled us to monitor Arc gene expression dynamics in vivo, over an area that included the whole of the dorsal cerebral cortex. Moreover, we were able to perform three-dimensional analyses of activated regions using paraformaldehyde-fixed brains. In addition to the visual cortex, we found that the cingulate cortex was strongly activated by light stimuli. These mice are extremely useful for the functional analysis of gene expression over extensive areas of the brains in both wild-type mice and mutants with impaired brain function.     

Degradation kinetics of methionine5-enkephalin by select brain areas from patients with chronic schizophrenia

After 10-minute incubation of [3H]-tyrosine methionine-enkephalin (MET) with 100,000 x g supernatant from select brain regions of patients with chronic schizophrenia (n = 3), essentially all of the labeled tyrosine was recovered as the free amino acid. Initial velocity and half-life of MET degradation obtained from different brain areas (limbic system, thalamus, basal ganglia, cerebellum, and cortex) of individual brains or from equivalent sections from different brains were scattered and considerable spread out (brains A, B, and C: 21.7-60.2 and 2.1-14.3, 25.6-88.7 and 1.6-14.1, 24.5-56.1 and 2.6-14.3 pg MET/mg brain tissue/min and min, respectively; brains A-C range, 21.7-88.7 pg MET/mg brain tissue/min and 1.6-14.3 min, respectively). These results failed to identify consistent differences in peptide degradation kinetics between the various brains areas studied from the same individual or from equivalent section from different subjects. MET metabolic rate was pH and temperature-dependent (optimum 7.4 degrees C and 37 degrees C), reduced by the aminopeptidase inhibitors puromycin, bacitracin, and bestatin, and to a lesser extent by thioridazine. However, peptide metabolism was not significantly affected by differences in tissue storage time or repeated freezing and thawing; by preincubation with N-carboxymethyl phenyl leucine, captopril, or thiorphan (dipeptidyl peptidase[s] or peptidyl dipeptidase[s] inhibitors, respectively); or by the many different drugs used by the patients with chronic schizophrenia. Our findings, although of a preliminary nature and generally similar to those recently reported for comparable studies on nonneuropsychiatric patients, provide a much needed understanding of the mechanisms regulating brain MET metabolism. Whether these results may contribute to the rational design of pharmacologic strategies for the treatment of pathologies associated with alterations in the enkephalinergic system needs further research.     

Abnormalities in gangliosides and other lipids of monkey, rabbit and human brains with chronic organic mercury intoxication

The distribution patterns of gangliosides and other major lipids in the monkey, rabbit and human brains with chronic organic mercury intoxication were examined. Various areas of the monkey brains were tested for alterations in the lipid composition in detail. Phosphatidylethanolamine and phosphatidylcholine slightly decreased, and sphingomyelin increased in all the areas tested of the intoxicated brains. The total ganglioside concentration was elevated in the frontal and basal ganglia gray matter tissues. In the percentage distribution of gangliosides, GD1b, GT1b and GQ1b (B pathway, [19, 20]) increased, while GM2, GM1 and GD1a (A pathway, [19, 20]) decreased. Similar ganglioside pattern changes were observed also in a human brain and in a rabbit brain with chronic organic mercury intoxication. The altered distribution patterns of gangliosides may be attributable to the proliferation of reactive astrocytes due to organic mercury.     

Development of cerebral fiber pathways in cats revealed by diffusion spectrum imaging

Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. By tracing fiber pathways throughout the entire brain, diffusion tractography provides information that cannot be achieved by conventional anatomical MR imaging or histology. However, standard diffusion tractography (based on diffusion tensor imaging, or DTI) tends to terminate in brain areas with low water diffusivity, indexed by low diffusion fractional anisotropy (FA), which can be caused by crossing fibers as well as fibers with less myelin. For this reason, DTI tractography is not effective for delineating the structural changes that occur in the developing brain, where the process of myelination is incomplete, and where crossing fibers exist in greater numbers than in the adult brain. Unlike DTI, diffusion spectrum imaging (DSI) can define multiple directions of water diffusivity; as such, diffusion tractography based on DSI provides marked flexibility for delineation of fiber tracts in areas where the fiber architecture is complex and multidirectional, even in areas of low FA. In this study, we showed that FA values were lower in the white matter of newborn (postnatal day 0; P0) cat brains than in the white matter of infant (P35) and juvenile (P100) cat brains. These results correlated well with histological myelin stains of the white matter: the newborn kitten brain has much less myelin than that found in cat brains at later stages of development. Using DSI tractography, we successfully identified structural changes in thalamo-cortical and cortico-cortical association tracts in cat brains from one stage of development to another. In newborns, the main body of the thalamo-cortical tract was smooth, and fibers branching from it were almost straight, while the main body became more complex and branching fibers became curved reflecting gyrification in the older cats. Cortico-cortical tracts in the temporal lobe were smooth in newborns, and they formed a sharper angle in the later stages of development. The cingulum bundle and superior longitudinal fasciculus became more visible with time. Within the first month after birth, structural changes occurred in these tracts that coincided with the formation of the gyri. These results show that DSI tractography has the potential for mapping morphological changes in low FA areas associated with growth and development. The technique may also be applicable to the study of other forms of brain plasticity, including future studies in vivo.     

3H-delta9-tetrahydrocannabinol tissue and subcellular distribution in the central nervous system and tissue distribution in peripheral organs of tolerant and nontolerant dogs.

Tolerant and nontolerant dogs received one i.v. administration of 0.5 mg/kg of 3H-delta9-tetrahydrocannabinol 30 minutes before they were sacrificed. Plasma, peripheral and brain tissues, as well as subcellular fractions of brain tissues from both treatment groups, were analyzed for radioactivity. Throughout the time period before sacrifice, the plasma concentrations of radioactivity in the tolerant and nontolerant dogs were not significantly different. The percentage of radioactivity in brain and plasma that was due to either unchanged delta9-tetrahydrocannabinol or a major metabolite was the same in each group. Of the radioactivity in brain, 46% was identified as delta9-tetrahydrocannabinol. Regardless of treatment, there was a specific accumulation of radioactivity in adrenals, liver, kidney, heart and pancreas. The only significant differences in radioactivity between tolerant and nontolerant peripheral tissues were found in liver, kidney cortex, heart and lymph nodes. Although all brain areas from tolerant dogs contained less radioactivity than the comparable brain areas from nontolerant animals, only pituitary and putamen were significantly less. There was a specific accumulation of radioactivity in some brain areas that could be associated with behavioral effects. The concentration in cerebellar and cerebral gray was significantly greater than that in white, and there was a marked reduction in the concentration in gray after tolerance developed. The mean percentage of radioactivity in each subcellular fraction was as follows: 23% crude nuclei, 44% mitochondria, 8% cholinergic nerve endings, 7% noncholinergic nerve endings, 2% free mitochondria and 6% synaptic vesicles. The quantity of radioactivity in homogenates of brains from tolerant dogs was 17% less than brains of nontolerant animals, which was merely a reflection of the respective plasma concentrations. The distribution of radioactivity was similar in both groups, although most of the subcellular fractions from tolerant dogs contained a lesser amount of radioactivity. The most notable difference was observed in the synaptic vesicle fraction. The synaptic vesicle fraction of tolerant dogs contained 40% less radioactivity than did the same fraction from nontolerant dogs, which implied a possible mechanism of action. A comparison of the remaining subcellular fractions did not appear to explain the development of tolerance.     

Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable?

Studies on structural-functional associations in the visual system require precise information on the location and variability of Brodmann's areas 17 and 18. Usually, these studies are based on the Talairach atlas, which does not rely on cytoarchitectonic observations, but on comparisons of macroscopic features in the Talairach brain and Brodmann's drawing. In addition, in this atlas are found only the approximate positions of cytoarchitectonic areas and not the exact borders. We have cytoarchitectonically mapped both areas in 10 human brains and marked their borders in corresponding computerized images. Borders were defined on the basis of quantitative cytoarchitecture and multivariate statistics. In addition to borders of areas 17 and 18, subparcellations within both areas were found. The cytoarchitectonically defined areas were 3-D reconstructed and transferred into the stereotaxic space of the standard reference brain. Surface rendering of the brains revealed high individual variability in size and shape of the areas and in the relationship to the free surface and sulci. Ranges and centers of gravity of both areas were calculated in Talairach coordinates. The positions of areas 17 and 18 in the stereotaxic space differed between the hemispheres. Both areas reached significantly more caudal and medial positions on the left than on the right. Probability maps were created in which the degree of overlap in each stereotaxic position was quantified. These maps of areas 17 and 18 are the first of their kind and contain precise stereotaxic information on both interhemispheric and interindividual differences.     

Mammalian brain consumption by blood donors in the United States: brains today,deferred tomorrow?

BACKGROUND: Theoretical concerns of possible variant CJD (vCJD) transmission by transfusion have led to deferral of US donors potentially exposed to the bovine spongiform encephalopathy agent. Although the efficacy of these policies is unknown, impact on blood collections has been substantial. Under the precautionary principle, deferral of donors consuming bovine (or other mam-malian) brains, possibly contaminated with the vCJD agent, might be considered. Blood donors were surveyed to determine lifetime mammalian brain consumption. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study (REDS) conducted an anonymous mail survey of 92,581 donors from eight US blood centers. RESULTS: Responses were received from 52,650 donors (57%). Of these, 6.4 percent reported lifetime brain consumption; bovine (3.6%) and hog brains (1.7%) were the most common. Bovine brain consumption varied fourfold by center (1.7-7.0%) and was highest among male (4.5%), older (age 55+, 6.5%), foreign-born (9.2%), Asian (7.2%), and Hispanic (8.6%) donors. Among bovine brain consumers, 67 percent engaged in the practice 4 times or less, 79 percent were repeat donors, and 61 percent reported giving at least 11 donations in the past 10 years. CONCLUSION: Following the precautionary principle, further steps to reduce the theoretical vCJD risk could include deferring donors who eat bovine (or other mammalian) brains. The impact of such a policy would not be trivial, especially in areas with older, foreign-born, Asian, or Hispanic donors. Cautious implementation and periodic evaluation of deferral policies is warranted.     

Atlas of the rat brain: quantitative distribution of the choline acetyltransferase.

We have developed a fluorescence microphotometry system for microanalysis of the quantitative distribution of neurotransmitters and their related chemical substances in the brain slice. In the present study, the extensive distributions of cholinergic systems were analyzed quantitatively and in detail throughout the rat whole brains by this novel method through immunohistochemical staining of choline acetyltransferase (CAT). The rat whole brain was slice coronally and continuously, and 50 slices were chosen at approximately 500 microns intervals and stained immunohistochemically for CAT. Immunohistochemical fluorescence intensities were measured through a 6 microns phi (on the slice) pinhole of a microscope, the brain slice was moved along the X- or Y-axes stepwise at 40 microns intervals under the objective lens of the microscope, and the distributions of fluorescence intensities were analyzed over the entire surface of the slice. The brain was divided into approximately 5,000,000 areas, and immunohistochemical fluorescence intensities of those areas were quantitatively measured. The obtained fluorescence intensities of CAT were classified into 8 ranks and were indicated by color coding and by three-dimensional graphics. Also, the actual fluorescence intensity values in large brain regions were presented. This type of brain atlas of the neurotransmitter or its related chemical substances provides very important information on their dynamics in the brain under experimental as well as pathological conditions. Also, this quantitative and detailed analysis is useful for combining morphological data with those from neurochemical and behavioral analyses of brain function.     

Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies.

Chronic administration of nicotine increases the density of neuronal cholinergic nicotinic receptors in cells and in rodent brain, and similar increases have been reported in brains from human smokers. To further examine this phenomenon, we measured nicotinic receptor binding sites in brain regions from matched populations of smokers and nonsmokers. We first measured binding of [3H](+/-)epibatidine ([3H]EB) and [3H]cytisine in homogenate preparations from samples of prefrontal and temporal cerebral cortex. Binding of each radioligand was significantly higher (250-300%) in both cortical regions from brains of smokers. Frozen sections from each of the cerebral cortical regions and the hippocampus were used for autoradiographic analysis of [3H]EB binding. In cerebral cortex, binding was most dense in layer VI in the prefrontal cortex and layers IV and VI in the temporal cortex. Densitometric analysis of [3H]EB binding sites revealed marked increases of 300 to 400% of control in all cortical regions examined from smokers' brains. Binding in the hippocampal formation was heterogeneously distributed, with dense areas of binding sites seen in the parasubiculum, subiculum, and molecular layer of the dentate gyrus, and the lacunosum-moleculare layer of the CA1/2. Binding of [3H]EB was significantly higher in all six regions of the hippocampus examined from brains of smokers compared with nonsmokers. These increases ranged from 160% of control in parasubiculum to 290% in the molecular layer of the dentate gyrus. The increase in nicotinic receptors in the cerebral cortex and hippocampus of smokers may modify the central nervous system effects of nicotine and contribute to an altered response of smokers to nicotine.     

3-methyl-3-butenoic acid: an artefact in the urinary metabolic pattern of patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

A method for isolation of two multiple sclerosis(MS)-specific brain antigens [3] is described. The brain cytosol was passed through a Con A-Sepharose column and the glycoproteins containing MS-specific antigens (MSG) were eluted with 50 mmol/l methyl-α-d-glucopyranoside, pH 6. By fractionation of MSG on DEAE-cellulose, a fraction containing MS-specific antigens (MSG2) was eluted in 0.25 mol/l NaCl, after prior elution of other proteins with distilled water. The MS specific antigens in the MSG2 fraction were traced and characterized by crossed immunoelectrophoresis and isoelectric focusing. A quantitative determination of proteins eluted in MSG2 revealed that the 2 MS-specific antigens had been purified 10 000 times.Using this method to isolate the two MS-specific antigens of autopsy brains, they were found to be present in $\text{7}\text{7}$ MS brains and absent in $\text{9}\text{9}$ non-MS brains studied. The method described in the present communication may be used both for the partial purification of the MS-specific antigens as well as for the tracing of the specific antigens in different topographical areas of the MS brains.     

基于Rs-fMRI的维、汉语脑卒中后失语症患者的脑功能研究

目的 利用静息态功能磁共振成像技术（Rs-fMRI）研究维族和汉族脑卒中失语症患者在静息态下脑自发活动的差异区,并初步探讨形成差异的原因。 方法 利用Rs-fMRI采集15例汉族脑卒中失语症患者（汉语组）和12例维族脑卒中失语症患者（维语组）静息态下的fMRI数据,对数据预处理后进行低频振幅（ALFF）指标的计算,最后对两组数据做组间统计学比较。 结果 静息状态下汉语患者的ALFF大于维语患者,汉语患者的右侧丘脑ALFF值增加。 结论 在静息态下汉族失语症患者的右侧丘脑处ALFF大于维族患者,可能是由于汉族患者左侧脑区脑卒中后,右侧丘脑部分参与了新的语言回路,对语言功能的损失起到了一定的代偿作用。     

Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis

Elevated cerebrospinal fluid (CSF) IgG and oligoclonal IgG bands on electrophoresis are valuable clinical markers for B cell proliferation in the brains of patients with multiple sclerosis (MS). Using two-dimensional electrophoresis, (2DE) we have established that the humoral immune response in MS brain is characterized by finite clonal complexity for the major Ig classes. An important question is whether this immune response is clonally stable or varies with time, related to the development of new lesions and random entry of B cells into the MS brain. To investigate this, we performed serial electrophoretic studies on CSF obtained from 19 patients with MS; the intervals ranged from 7 to 12 yr, with a mean of 8 yr. These analyses included studies of IgG, IgA, and IgM, and revealed that the humoral immune response in MS is clonally stable over long periods. Spontaneous fluctuations or reduction in CSF IgG levels by drugs did not qualitatively affect B cell clonal proliferation in MS brain, in that dominant bands and spots were not obliterated. It has been asserted that IgG synthesis in MS is nonsense antibody because the spectotypes of IgG isolated from different regions of MS brains differ. Factors other than clonal heterogeneity could account for differences found using one-dimensional analysis. B cell clonal products resolve into unique and well-resolved spots by 2DE; the method is uniquely suitable for analysis of restricted immune responses. Therefore, Ig were isolated from 11 regions of three MS brains and the 2DE patterns were compared. The similarity of the 2DE patterns indicate unequivocally that major clones are distributed uniformly although some clones are more prominent in some brain areas. IgA and IgM isolated from the same areas also showed similar patterns. Furthermore, the patterns of light and heavy chains in brain regions differed from serum but were similar to the autologous CSF, providing new evidence that CSF IgG in MS derives from synthesis in situ. Our results indicate that, once initiated, B cell clonal proliferation persists indefinitely and is little altered qualitatively at a clonal level over time, even when CSF IgG levels change or are altered by drugs. Our results are consistent with allotype and idiotype analysis of Ig production in MS and conflict with nonsense antibody proposals of the origin and nature of in situ synthesized Ig in MS.     

汉语言自由联想功能磁共振的初步研究

目的设计一种适合汉语言自由联想的脑功能磁共振刺激任务,探索汉语言自由联想脑功能区表现。材料与方法对19名健康汉语志愿者进行任务态自由联想语言功能刺激,同时采集功能性磁共振成像(functional magnetic resonance imaging,f MRI)数据,通过SPM8软件分析获取自由联想任务相关主要脑功能区位置,激活大小及最大激活强度。结果汉语自由联想主效应区位于右颞上回(BA21);左颞枕内侧回、左海马旁回在联想任务中没有激活信号,双侧海马的激活程度较低。结论利用该语言任务能激活正常人自由联想语言功能区;同时血氧水平依赖性功能磁共振成像(blood oxygen level dependent functional magnetic resonance imaging,BOLD-f MRI)可以准确定位激活区,量化激活区大小及最大激活强度,技术稳定可靠,适用于汉语言联想相关脑功能区疾病研究。     

Brain density and symmetry in pedophilic and sexually aggressive offenders

Brain area and optical density were computed for each hemisphere and for 4 sections within the hemispheres at the level of the temporal horns for 18 pedophiles, 12 incest offenders, 34 sexually aggressive offenders of adult females and 12 nonviolent nonsex offender controls. Brain length and width was also computed, using the pineal gland as reference. From the width measures, an index of brain symmetry was computed. Results showed that the brains of sex offenders were relatively smaller in the left hemisphere compared to controls, but there were no significant group differences in optical density. There were no subgroup differences in brain area but the segments corresponding to the left frontal and temporal areas were smaller in sex offenders than controls. There were no significant differences in brain length but sex offenders had smaller widths in both hemispheres than controls. Analysis of symmetry showed that 66.7% of pedophiles and 53.1% of sexual aggressives had asymmetric brains compared to 8.3% of incest offenders and 20.0% of controls. Pedophiles showed smaller left hemispheres than right whereas sexual aggressives were equally split between left and right asymmetry. These results support earlier findings of temporal horn dilatation in pedophiles and sexual aggressives.     

Replicable functional magnetic resonance imaging evidence of correlated brain signals between physically and sensory isolated subjects

OBJECTIVES: Previous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) experiments have suggested that correlated neural signals may be detected in the brains of individuals who are physically and sensorily isolated from each other. Functional MRI and EEG methods were used in the present study in an attempt to replicate these findings. DESIGN/SETTINGS: Subjects were electrically and magnetically shielded because of the characteristic surroundings of the scanner room. During the experiment, the nonstimulated subject was placed in the scanner with sensory isolating goggles covering the subject's eyes. The stimulated subject was placed 30 feet away and sat in front of a video monitor that presented an alternating schedule of six stimulus-on/stimulus-off conditions. The stimulus- on condition consisted of a flickering checkerboard pattern whereas the stimulus-off condition consisted of a static checkerboard. Stimulus-on/-off conditions were presented in the sequence on/off/on/off/on/off. The duration of these intervals was randomly assigned but consistently provided a total of 150 seconds of flicker and 150 seconds of static. Sessions were repeated twice to assess possible replication of the phenomenon. OUTCOME MEASURES: Changes in fMRI brain activation (relating to blood oxygenation) and EEG signals were measured in the nonstimulated subjects. Changes occurring during stimulus-on conditions were statistically compared to changes occurring during the stimulus-off conditions. RESULTS: Statistically significant changes in fMRI brain activation and EEG signals were observed when comparing the stimulus-on condition to the stimulus-off condition in nonstimulated subjects (p < 0.001, corrected for multiple comparisons). For fMRI, these changes were observed in visual brain areas 18 and 19 (Brodmann areas). One of the subjects replicated the results. CONCLUSIONS: These data replicate previous findings suggesting that correlated neural signals may be detected by fMRI and EEG in the brains of subjects who are physically and sensorily isolated from each other.     

胱天蛋白酶3在啮齿类动物和猕猴脑中的表达:种系和年龄相关研究

背景:有研究显示,凋亡相关蛋白酶—胱天蛋白酶3被认为是动物和人脑中细胞凋亡过程中的关键酶,正常人或阿尔茨海默病患者的脑中有该酶的表达,这与对成年啮齿动物脑研究的结果之间存在着矛盾。目的:揭示胱天蛋白酶3在啮齿类动物和猕猴脑中的表达有无差异,分析该酶在猕猴脑中的表达水平有无年龄差异,以及不同猕猴脑区间有无差别。设计:单变量均数的平行比较。单位:解放军总医院肝胆外科研究所,香港中文大学解剖学系。材料:实验于2003-08/2005-02在解放军总医院肝胆外科研究所及香港中文大学解剖学系进行的,所用的2,12,24和48周龄(每周龄组n=5)SD大鼠、ICR小鼠和快速衰老小鼠(senescence-acceleratedmice,SAM),雌雄不限,由香港中文大学实验动物服务中心提供;健康雌性4岁和20岁猕猴各4只,均购自解放军总医院医学实验动物中心(SCXK-(京)2003-002)。以上动物均在无任何实验干预的标准条件下养殖。方法:①所有脑组织标本均从猕猴和啮齿动物中新鲜切取,制成匀浆后通过免疫印迹法检测啮齿类动物和猕猴脑组织中胱天蛋白酶3蛋白的表达;②用同样的方法比较两个年龄组猕猴的大脑皮质、海马和小脑中该蛋白的表达量,并通过免疫组织化学法显示胱天蛋白酶3在猕猴3个脑区中的细胞分布状态。主要观察指标:①胱天蛋白酶3在啮齿类动物和猕猴脑中的免疫印迹检测;②胱天蛋白酶3在猕猴3个脑区中的细胞分布状态。结果:①免疫印迹检测结果:胱天蛋白酶3在3种2周龄的鼠脑中表达模式相同,在其它年长鼠脑中未检测到该酶;胱天蛋白酶3在成年和老年猕猴脑中均有持续表达,表达量低于2周龄鼠。胱天蛋白酶3在猴脑中以酶原(Mr32000)的形式存在,未发现该酶在猕猴脑中的表达量有年龄和脑区差异。②免疫组织化学法显示结果:猕猴大脑皮质胱天蛋白酶3的免疫反应性很低,海马的CA1、CA3和CA4区可见低至中度阳性染色的锥体细胞,小脑皮质的少数浦肯野氏细胞呈强阳性染色。老年猕猴除运动皮质第V层偶见呈强阳性染色的大锥体细胞外,其余与成年猴无明显差别。结论:啮齿类动物成年后,脑中胱天蛋白酶3的表达迅速下降至测不出,而该酶在成年及老年猕猴脑中仍维持在一定水平,其表达量和阳性细胞的分布状态无明显的年龄差异。     

Effects of spatial transformation on regional brain volume estimates

Spatial transformation of MR brain images is a standard tool used in automated anatomical parcellation and other quantitative and qualitative methods to assess brain tissue volume, composition, and distribution. Despite widespread use, the quantitative effects of spatial transformation on regional brain volume estimates have been little studied. We report on the effects of transformation on regional brain volumes of 38 (17M, 21F) manually parcellated brains. After tracing in native space, regions of interest were transformed using a classic piecewise-linear Talairach transformation (Tal) or a nonlinear registration (AIR 5th order nonlinear algorithm, 158 parameters) to one of three Talairach-based templates: 1) Tal50, constructed from 50 Talairach-transformed normal brains, 2) the MNI 305 atlas, 3) IA38, constructed from MNI305-transformed scans of the 38 subjects used in this study. Native volumes were compared to the transformed volumes. We found that: 1) significant group-level differences can be obtained in transformed data sets that are in the opposite direction of effects obtained in native space; 2) the effects of transformation are heterogeneous across brain regions, even after covarying for total brain volume and age; 3) volumetric intra-class correlations between native and transformed brains differ by registration method and template choice, region, and tissue type; and 4) transformed brains produced hippocampus and corpus callosum volume proportions that were significantly different from those obtained in native space. Our results suggest that region-based volumetric differences uncovered by spatial-transformation-based methods should be replicated in native-space brains, and that meta-analyses should take into account whether volumes are determined using spatially-transformed images and/or specific automated methods.