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author:("bone, William")
1.  Larger putamen size in antipsychotic-naïve individuals with schizotypal personality disorder 
Schizophrenia research  2012;143(1):158-164.
Objective
To (a) compare the size of the dorsal and ventral striatum(caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD.
Methods
The left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group × Region (caudate, putamen) × Slice (1–5: ventral, 2, 3, 4, dorsal) × Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain.
Results
Primary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms.
Conclusions
Striatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis.
doi:10.1016/j.schres.2012.11.003
PMCID: PMC3634353  PMID: 23187070
Schizotypal personality disorder; Putamen; Caudate; Striatum; Schizophrenia; MRI; Striatal size
2.  Anterior limb of the internal capsule in schizotypal personality disorder: Fiber-tract counting, volume, and anisotropy 
Schizophrenia research  2012;141(0):119-127.
Mounting evidence suggests that white matter abnormalities and altered subcortical–cortical connectivity may be central to the pathology of schizophrenia (SZ). The anterior limb of the internal capsule (ALIC) is an important thalamo-frontal white-matter tract shown to have volume reductions in SZ and to a lesser degree in schizotypal personality disorder (SPD). While fractional anisotropy (FA) and connectivity abnormalities in the ALIC have been reported in SZ, they have not been examined in SPD. In the current study, magnetic resonance (MRI) and diffusion tensor imaging (DTI) were obtained in age- and sex-matched individuals with SPD (n=33) and healthy controls (HCs; n=38). The ALIC was traced bilaterally on five equally spaced dorsal-to-ventral axial slices from each participant’s MRI scan and co-registered to DTI for the calculation of FA. Tractography was used to examine tracts between the ALIC and two key Brodmann areas (BAs; BA10, BA45) within the dorsolateral prefrontal cortex (DLPFC). Compared with HCs, the SPD participants exhibited (a) smaller relative volume at the mid-ventral ALIC slice level but not the other levels; (b) normal FA within the ALIC; (c) fewer relative number of tracts between the most-dorsal ALIC levels and BA10 but not BA45 and (d) fewer dorsal ALIC–DLPFC tracts were associated with greater symptom severity in SPD. In contrast to prior SZ studies that report lower FA, individuals with SPD show sparing. Our findings are consistent with a pattern of milder thalamo-frontal dysconnectivity in SPD than schizophrenia.
doi:10.1016/j.schres.2012.08.022
PMCID: PMC3742803  PMID: 22995934
Schizotypal personality disorder; Diffusion tensor imaging; Tractography; Magnetic resonance imaging; Anisotropy; Internal capsule
3.  Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites 
Nucleic Acids Research  2013;42(1):109-127.
We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island–containing promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and non–neuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells.
doi:10.1093/nar/gkt838
PMCID: PMC3874157  PMID: 24057217
4.  Anterior and Posterior Cingulate Cortex Volume in Healthy Adults: Effects of Aging and Gender Differences 
Brain research  2011;1401:18-29.
The cingulate cortex frequently shows gray matter loss with age as well as gender differences in structure and function, but little is known about whether individual cingulate Brodmann areas show gender-specific patterns of age-related volume decline. This study examined age-related changes, gender differences, and the interaction of age and gender in the relative volume of cingulate gray matter in areas 25, 24, 31, 23, and 29, over seven decades of adulthood. Participants included healthy, age-matched men and women, aged 20–87 (n = 70). Main findings were: (1) The whole cingulate showed significant age-related volume declines (averaging 5.54% decline between decades, 20s–80s). Each of the five cingulate areas also showed a significant decline with age, and individual areas showed different patterns of decline across the decades: Smaller volume with age was most evident in area 31, followed by 25 and 24. (2) Women had relatively larger cingulate gray matter volume than men overall and in area 24. (3) Men and women showed different patterns of age-related volume decline in area 31, at midlife and late in life. By delineating normal gender differences and age-related morphometric changes in the cingulate cortex over seven decades of adulthood, this study improves the baseline for comparison with structural irregularities in the cingulate cortex associated with psychopathology. The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function.
doi:10.1016/j.brainres.2011.05.050
PMCID: PMC3134959  PMID: 21669408
Cingulate cortex; aging; gender differences; MRI; gray matter; morphometry
5.  Astrocyte and Glutamate Markers in the Superficial, Deep, and White Matter Layers of the Anterior Cingulate Gyrus in Schizophrenia 
Neuropsychopharmacology  2011;36(6):1171-1177.
Most studies of the neurobiology of schizophrenia have focused on neurotransmitter systems, their receptors, and downstream effectors. Recent evidence suggests that it is no longer tenable to consider neurons and their functions independently of the glia that interact with them. Although astrocytes have been viewed as harbingers of neuronal injury and CNS stress, their principal functions include maintenance of glutamate homeostasis and recycling, mediation of saltatory conduction, and even direct neurotransmission. Results of studies of astrocytes in schizophrenia have been variable, in part because of the assessment of single and not necessarily universal markers and/or assessment of non-discrete brain regions. We used laser capture microdissection to study three distinct partitions of the anterior cingulate gyrus (layers I–III, IV–VI, and the underlying white matter) in the brains of 18 well-characterized persons with schizophrenia and 21 unaffected comparison controls. We studied the mRNA expression of nine specific markers known to be localized to astrocytes. The expression of astrocyte markers was not altered in the superficial layers or the underlying white matter of the cingulate cortex of persons with schizophrenia. However, the expression of some astrocyte markers (diodinase type II, aquaporin-4, S100β, glutaminase, excitatory amino-acid transporter 2, and thrombospondin), but not of others (aldehyde dehydrogenase 1 family member L1, glial fibrillary acidic protein, and vimentin) was significantly reduced in the deep layers of the anterior cingulate gyrus. These findings suggest that a subset of astrocytes localized to specific cortical layers is adversely affected in schizophrenia and raise the possibility of glutamatergic dyshomeostasis in selected neuronal populations.
doi:10.1038/npp.2010.252
PMCID: PMC3077461  PMID: 21270770
astrocytes; cortical layers; postmortem; mRNA; schizophrenia; molecular & cellular neurobiology; biological psychiatry; neuroanatomy; neurotransmitters; glia; postmortem; astrocyte; schizophrenia; cingulate
6.  Cingulate and Temporal Lobe Fractional Anisotropy in Schizotypal Personality Disorder 
Neuroimage  2011;55(3):900-908.
Background
Consistent with the clinical picture of milder symptomatology in schizotypal personality disorder (SPD) than schizophrenia, morphological studies indicate SPD abnormalities in temporal lobe regions but to a much lesser extent in prefrontal regions implicated in schizophrenia. Lower fractional anisotropy (FA), a measure of white-matter integrity within prefrontal, temporal, and cingulate regions has been reported in schizophrenia but has been little studied in SPD.
Aims
To examine temporal and prefrontal FA in 30 neuroleptic-naïve SPD patients and 35 matched healthy controls. We hypothesized that compared with healthy controls (HCs), SPD patients would exhibit lower FA in temporal and anterior cingulum regions but relative sparing in prefrontal regions.
Method
We acquired diffusion tensor imaging (DTI) in all participants and examined FA in the white matter underlying Brodmann areas (BAs) in dorsolateral prefrontal (BA44,45,46), temporal (BA22,21,20), and cingulum (BA25,24,31,23,29) regions using multivariate-ANOVAs.
Results
Compared with healthy controls, the SPD group had significantly lower FA in left temporal but not prefrontal regions. In the cingulum, FA was lower in the SPD group in posterior regions (BA31 and 23), higher in anterior (BA25) regions and lower overall in the right but not left cingulum. Among the SPD group, lower FA in the cingulum was associated with more severe negative symptoms (e.g., odd speech).
Conclusions
Similar to schizophrenia, our results indicate cingulum-temporal lobe FA abnormalities in SPD and suggest that cingulum abnormalities are associated with negative symptoms.
doi:10.1016/j.neuroimage.2010.12.082
PMCID: PMC3262398  PMID: 21223999
Diffusion tensor imaging; schizotypal personality disorder; dorsolateral prefrontal cortex; temporal lobe; cingulum; fractional anisotropy
7.  Astrocyte and glutamate markers in the superficial, deep and white matter layers of the anterior cingulate gyrus in schizophrenia 
Most studies of the neurobiology of schizophrenia have focused on neurotransmitter systems, their receptors and downstream effectors. Recent evidence suggests that it is no longer tenable to consider neurons and their functions independently of the glia that interact with them. Although astrocytes have been viewed as harbingers of neuronal injury and CNS stress, their principal functions include maintenance glutamate homeostasis and recycling, mediation of saltatory conduction and even direct neurotransmission. Results of studies of astrocytes in schizophrenia have been variable, in part due to the assessment of single and not necessarily universal markers and/or assessment of non-discrete brain regions. We used laser capture microdissection to study 3 distinct partitions of the anterior cingulate gyrus (layers I–III, IV–VI, underlying white matter) in the brains of 18 well-characterized persons with schizophrenia and 21 unaffected comparison controls. We studied the mRNA expression of 9 specific markers known to be localized to astrocytes. The expression of astrocyte markers was not altered in the superficial layers or the underlying white matter of the cingulate cortex of persons with schizophrenia. However the expression of some astrocyte markers (diodinase type II, aquaporin-4, S100β, glutaminase, excitatory amino acid transporter 2 and thrombospondin), but not to others (aldehyde dehydrogenase 1 family member L1, glial fibrillary acidic protein and vimentin) was significantly reduced in the deep layers of the anterior cingulate gyrus. These findings suggest that a subset of astrocytes localized to specific cortical layers are adversely affected in schizophrenia and raise the possibility of glutamatergic dyshomeostasis in selected neuronal populations.
doi:10.1038/npp.2010.252
PMCID: PMC3077461  PMID: 21270770
Astrocytes; cortical layers; postmortem; mRNA; schizophrenia
8.  Effects of sex and normal aging on regional brain activation during verbal memory performance 
Neurobiology of aging  2008;31(5):826-838.
This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using 18FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20–87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate—a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change.
doi:10.1016/j.neurobiolaging.2008.10.005
PMCID: PMC2871327  PMID: 19027195
Aging; healthy adults; sex differences; 18FDG PET; cingulate; prefrontal cortex
9.  Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia 
Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.
Electronic supplementary material
The online version of this article (doi:10.1007/s00406-011-0202-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s00406-011-0202-x
PMCID: PMC3182327  PMID: 21431919
Cerebral spinal fluid; Sulcal enlargement; Myelin; Fronto-thalamic connectivity
10.  Editing of Serotonin 2C Receptor mRNA in the Prefrontal Cortex Characterizes High Novelty Locomotor Response Behavioral Trait 
Serotonin 2C receptor (5-HT2CR) exerts a major inhibitory influence on dopamine (DA) neurotransmission within the mesocorticolimbic DA pathway that is implicated in drug reward and goal-directed behaviors. 5-HT2CR pre-mRNA undergoes adenosine-to-inosine editing generating numerous receptor isoforms in brain. Because editing influences 5-HT2CR efficacy, individual differences in editing might influence dopaminergic function and, thereby, contribute to inter-individual vulnerability to drug addiction.
Liability to drug-related behaviors in rats can be predicted by the level of motor activity in response to a novel environment. Rats with a high locomotor response (high responders; HRs) exhibit enhanced acquisition and maintenance of drug self-administration compared to rats with a low response (low responders; LRs). Here we examined 5-HT2CR mRNA editing and expression in HR and LR phenotypes in order to investigate the relationship between 5-HT2CR function and behavioral traits relevant to drug addiction vulnerability. Three regions of the mesocorticolimbic circuitry (ventral tegmental area (VTA), nucleus accumbens (NuAc) shell, and medial prefrontal cortex (PFC)) were examined.
5-HT2CR mRNA expression and editing was significantly higher in NuAc shell compared to both PFC and VTA, implying significant differences in function (including constitutive activity) among 5-HT2CR neuronal populations within the circuitry. The regional differences in editing could, at least in part, arise from the variations in expression levels of the editing enzyme, ADAR2, and/or from the variations in the ADAR2/ADAR1 ratio observed in the study. No differences in the 5-HT2CR expression were detected between the behavioral phenotypes. However, editing was higher in the PFC of HRs vs. LRs, implicating this region in the pathophysiology of drug abuse liability.
doi:10.1038/npp.2009.51
PMCID: PMC2735076  PMID: 19494808
serotonin 2C receptor; mRNA editing; drug addiction; rat; high and low responders; prefrontal cortex
11.  Diffusion Tensor Anisotropy in Adolescents and Adults 
Neuropsychobiology  2007;55(2):96-111.
We acquired diffusion tensor images on 33 normal adults aged 22–64 and 15 adolescents aged 14–21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.
doi:10.1159/000104277
PMCID: PMC2806688  PMID: 17587876
Age; White matter; Magnetic resonance imaging
12.  Effects of Mental Illness and Aging in Two Thalamic Nuclei 
Schizophrenia research  2008;106(2-3):172-181.
We previously reported a schizophrenia associated reduction of neuronal and oligodendrocyte number in the anterior principal thalamic nucleus (APN) in a cohort of severely impaired elderly subjects with schizophrenia (SZ) relative to age matched nonpsychiatric controls (NCs). The present study was undertaken to determine 1) if those findings could be replicated in an independent sample of less chronically impaired subjects with SZ and NCs stratified across a broader age range; 2) if the findings are specific to SZ or are also seen in unipolar major depressive (MDD) or bipolar disorder (BPD); and 3) if the findings are specific to the APN or also seen in another thalamic nucleus. Computer assisted stereological methods were employed to determine the number of neurons and oligodendrocytes in the APN and centromedian nucleus (CMN) of the Nissl-stained thalamic sections maintained by the Stanley Foundation Brain Bank. This collection includes specimens from NCs and age matched subjects with diagnoses of SZ, MDD, or BPD who died between the ages of 25 and 68. Data were analyzed by mixed-effects linear regressions adjusting for demographic variables and known history of exposure to psychotropic medications.
Oligodendrocyte number was decreased in both nuclei relative to NCs in subjects with SZ and in that subset of subjects with BPD who had experienced psychotic episodes. Compared to NCs both of these patient groups also exhibited an attenuation of an age-related increase in the number of oligodendrocytes. Contrary to our previous report, we did not detect a SZ-associated deficit in neuronal number in the APN. A history of exposure to neuroleptics, however, was associated with a decrease in neuronal number in both nuclei, but this decrease did not vary in relation to cumulative lifetime neuroleptic exposure in fluphenazine equivalents. Among subjects with psychiatric diagnoses, exposure to lithium was associated with an increase in the number of oligodendrocytes. No effects were detected for exposure to anticonvulsants or for abuse of alcohol or other substances.
doi:10.1016/j.schres.2008.08.023
PMCID: PMC2629743  PMID: 18835520
13.  IONOTROPIC GLUTAMATE RECEPTORS mRNA EXPRESSION IN THE HUMAN THALAMUS: ABSENCE OF CHANGE IN SCHIZOPHRENIA 
Brain research  2008;1214:23-34.
Abnormalities in glutamate neurotransmission are thought to be among the major contributing factors to the pathophysiology of schizophrenia. Although schizophrenia has been regarded mostly as a disorder of higher cortical function, the cortex and thalamus work as a functional unit. Existing data regarding alterations of glutamate receptor subunit expression in the thalamus in schizophrenia remain equivocal. This postmortem study examined mRNA expression of ionotropic glutamate receptor (iGluR) subunits and PSD95 in 5 precisely defined and dissected thalamic subdivisions (medial and lateral sectors of the mediodorsal nucleus; and the ventrolateral posterior, ventral posterior, and centromedian nuclei) of persons with schizophrenia and matched controls using quantitative PCR with normalization to multiple endogenous controls. Among 15 genes examined (NR1 and NR2A-D subunits of NMDA receptor; GluR1-4 subunits of AMPA receptor; GluR5-7 and KA1-2 subunits of kainate receptor; PSD95), all but two (GluR4 and KA1) were expressed at quantifiable levels. Differences in iGluR gene expression were seen between different nuclei but not between diagnostic groups. The relative abundance of transcripts was: NR1≫NR2A>NR2B>NR2D>NR2C for NMDA, GluR2>GluR1>GluR3 for AMPA, and KA2>GluR5>GluR7>GluR6 for kainate receptors. The expression of PSD95 correlated with the expression of NR1, NR2A, NR2B, NR2D and GluR6 in all nuclei. These results provide detailed and quantitative information on iGluR subunit expression in multiple nuclei of the human thalamus but suggest that alterations in their expression are not a prominent feature of schizophrenia.
doi:10.1016/j.brainres.2008.03.039
PMCID: PMC2678296  PMID: 18462708
Quantitative real-time PCR; Gene Expression; Laser Capture Microdissection; Thalamus; Schizophrenia; Glutamate Receptors
14.  Schizophrenia and Sex Associated Differences in the Expression of Neuronal and Oligodendrocyte Specific Genes in Individual Thalamic Nuclei 
Schizophrenia research  2007;98(1-3):118-128.
Considerable evidence based on the study of post-mortem brain tissue suggests deficits in both neuronal and myelin systems in schizophrenia (SZ). To date, most (may be “the majority of the”?) biochemical and molecular biological studies have focused on the cerebral cortex. Most information traveling to or from the cortex is relayed or synaptically gated through the thalamus, and numerous studies suggest structural and functional abnormalities in interconnected regions of the thalamus and cortex in SZ. The present study extends our gene expression studies of neuronal and myelin systems to the thalamus. Quantitative PCR was employed to assess the expression of 10 genes in 5 divisions of the thalamus which were precisely harvested using laser capture microdissection. The divisions studies were present on coronal sections at the level of the centromedian nucleus (CMN) taken from 14 schizophrenic and 16 normal control postmortem brains. The genes examined were specific for oligodendrocytes (MAG, CNP, MBP), neurons (ENO2), glutamatergic neurons (VGlut1, VGlut-2, PV, CB) or GABAergic neurons (GAD65, GAD67). Expression levels for each of these markers were quantitated and compared between diagnoses, between sexes, and across nuclei. CB was much more highly expressed in the CMN in SZs compared to NCs. No other diagnosis related differences in gene expression were observed. The expression levels of CNP and MAG, but not MBP, were highly correlated with one another and both, but not MBP, were much more highly expressed in females than in males in all thalamic divisions examined. All markers were differentially expressed across nuclei.
doi:10.1016/j.schres.2007.09.034
PMCID: PMC2678297  PMID: 18029146
Schizophrenia; Thalamus; Neurons; Oligodendrocytes; Gene Expression
15.  A New Antigen Retrieval Technique for Human Brain Tissue 
PLoS ONE  2008;3(10):e3378.
Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.
doi:10.1371/journal.pone.0003378
PMCID: PMC2566591  PMID: 18852880

Results 1-15 (15)