Normal Adult Human Brain Research Articles

Chemical and immunological characterization of galactosyl-beta 1-3-globoside in bovine, human, and rat brain.

Our studies of bovine brain neutral glycosphingolipids (Ngsls) have revealed the presence of several short-chain (containing -CHO 1-4) and previously uncharacterized long-chain (-CHO > 4-5) Ngsls. We reported the structural characterization of brain GgOse4Cer (GA1) and have now purified another brain Ngsl to homogeneity. The purified Ngsl migrated close to standard GgOse4Cer and nLcOse5Cer on a TLC plate employing two different solvent systems. The carbohydrate molar composition indicated the presence of Gal/Glc/GalNAc in a ratio of 2.8:1.0:0.9. Five permethylated alditol acetate peaks were characterized as 2,3,4,6-OMe4Gal, 2,4,6-OMe3Gal, 2,3,6-OMe3Gal, 2,3,6-OMe3Glc, and 4,6-OMe2GalNAcMe by gas chromatography-mass spectrometry. The anomeric carbohydrate sequence has been determined by specific exoglycosidase digestion. Six-hundred megahertz 1H NMR spectroscopy of the oligosaccharide released by ceramide glycanase hydrolysis confirmed the structure of the Ngsl as Gal beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer or IV3GalGbOse4Cer. Using the immunooverlay technique with anti-stage-specific embryonic antigen 3 antibody, it was found in bovine, rat, and normal adult human brain and bovine myelin, but not in human or rat myelin.

Calretinin-positive Cajal-Retzius cells persist in the adult human neocortex.

The occurrence of Cajal-Retzius (CjRe) cells was studied in four cortical areas of five normal adult humans using antibodies against calretinin. Calretinin immunofluorescence and autofluorescence of lipofusin granules in CjRe cells were visualized by dual channel confocal laser scanning microscopy. Three types of CjRe cells existed in the adult human cortex: horizontal, triangular and multipolar, and their number did not decrease with ageing. Horizontal CjRe cells were found in all cortical areas; they contained no lipofusin or less than other cells. Triangular CjRe cells with descending dendrites were less numerous. Multipolar CjRe cells were rare and contained more lipofuscin. We conclude that calretinin-immunoreactivity can be used to study CjRe cell morphology in normal and diseased adult human brain.

Differential expression of exons 10 and 11 in normal tau and tau associated with paired helical filaments.

Antibodies were raised to two synthetic peptides with amino acid sequences encoded by a variable region of exons 10 and 11 of the tau gene. The affinity-purified antibodies, designated E-10 and E-11, were used to determine whether PHF-tau and normal tau differ in variants containing three or four repeats in the microtubule-binding domain, respectively. Normal adult human brain was shown by gel electrophoresis to contain six isoforms of tau. All of the isoforms reacted with E-11, whereas only four of them with slower electrophoretic mobility were recognized by E-10. Fetal brain tau was readily recognized by E-11 but reacted poorly with E-10. In PHF preparations, E-11 bound to all three polypeptides of PHF-tau of 68 kD, 64 kD, and 60 kD and reacted intensely with a material smearing from the top of the gel to about the 50-kD region. In contrast, E-10 only weakly recognized the two higher molecular weight PHF-tau polypeptides of 68 kD and 64 kD, as well as smeared material, and the binding was not affected by phosphatase treatment. Using recombinant tau with four repeats as a reference, the immunoreactivity of E-10 with PHF-tau was estimated to be approximately 5% of that of E-11. By comparison, the immunoreactivity of E-10 with four isoforms of normal tau was comparable to that of E-11. These results indicate that the ratio of three vs. four repeat variants in PHF-tau is higher than in normal tau and suggest that Alzheimer disease may be associated with the disproportional expression of fetal (or juvenile) forms of tau. Alternatively, the weak reactivity of PHF-tau with E-10 antibody could be due to post-translational modifications other than phosphorylation.

Complementary distribution of tau proteins in different phosphorylation states within growing axons.

Microtubule-associated tau proteins are hyperphosphorylated in brains from patients with Alzheimer's disease compared with normal adult human brain. At least some of the phosphorylated residues are also transiently phosphorylated in juvenile brain, but not in more mature stages. Using the monoclonal anti-tau antibodies TAU-1 and AT8, we found in cultured embryonic chicken and rat neurones a clear differential distribution of immunostaining within growing axons. Tau proteins that are phosphorylated at Ser202 (recognized by AT8) appear to be concentrated in the axonal portion that is close to the cell body and they decrease in proximal-distal direction. In contrast, tau proteins carrying an epitope that contains dephospho-Ser202 (recognized by TAU-1) are enriched in the distal axon and the growth cone. In colchicine-treated, growth-inhibited neurones there was an intense TAU-1 staining of the perikarya, but no longer any staining by AT8.

Modulation of p36 gene expression in human neuronal cells

p36 is a calcium/lipid-binding phosphoprotein that is expressed at high levels in proliferating and transformed cells, and at low levels in terminally differentiated cells, such as CNS neurons. The calcium-dependent binding to membrane phospholipids, and its capacity to interact with intermediate filament proteins suggest that p36 may be involved in the transduction of extracellular signals. The present work examines p36 gene expression in the mature CNS, primary primitive neuroectodermal tumors (PNETs), and transformed PNET cell lines. p36 immunoreactivity was not observed in normal adult human brain, but low levels of the protein were detected by Western blot analysis. Following acute anoxic cerebral injury, the mean levels of p36 protein were elevated two-fold, and injured neurons exhibited increased p36 immunoreactivity. This phenomenon was likely to have been mediated by post-transcriptional mechanisms since there was no corresponding change in the level p36 mRNA. p36 immunoreactivity was detected in 8 of 9 primary PNETs, and in 3 of 3 neurofilament-expressing PNET cell lines. The levels of p36 protein in PNET cell lines were 5-fold higher than in adult human brain tissue. Although p36 gene expression was generally high in proliferating PNET cells, the levels of p36 mRNA and protein were not strictly correlated with DNA synthesis. Instead, p36 gene expression was modulated in both proliferating and non-proliferating PNET cell cultures by treatment with 50 mIU/ml of insulin, 100 mM ethanol, or 5 μM retinoic acid. The frequent discordances observed experimentally and in vivo between p36 mRNA and p36 protein expression suggest that the steady-state levels of p36 protein in neuronal cells may be regulated primarily by post-transcriptional mechanisms.

The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases.

The paired helical filaments (PHFs) in Alzheimer's disease neurofibrillary tangles are composed of PHF-tau which is thought to be hyperphosphorylated because several residues in postmortem samples of PHF-tau and human fetal tau are phosphorylated while the corresponding sites are not phosphorylated in autopsy-derived normal adult human brain tau. To determine how the phosphorylation of these sites is regulated, we isolated tau from rat brains at different embryonic and postnatal ages in the presence of okadaic acid to obtain tau in its most native in situ phosphorylation state. Fetal tau was highly phosphorylated from embryonic day 18 (E18) until postnatal day 11 (P11). Thereafter, the levels of fetal tau diminished as did its phosphorylation state concomitant with the appearance of the five adult tau isoforms. Several phosphorylation-dependent antibodies (i.e. AT270, AT8, AT180, T3P, and PHF1) that recognize PHF-tau also recognized these tau isoforms, albeit at reduced levels in the mature rat brain. This suggests that Thr172, Ser193, Thr222, Ser387, and Ser395 are normal sites of phosphorylation in rat brain tau. The inclusion of OK in the microtubule assembly buffers did not alter the ability of tau to bind microtubules at any age. However, phosphatases were activated and kinases were down-regulated in the rat brain after P12 since adult tau proteins were partially dephosphorylated at and beyond this time in the absence of OK. Protein phosphatase 2A (PP2A) and 2B (PP2B) activities in the adult rat brain extracts dephosphorylated tau efficiently, but protein phosphatases in extracts of the P6 rat brain did not have a similar effect. This suggests that the sensitivity of tau to OK after P12 may be regulated by the de novo induction of adult brain phosphatases. Finally, PP2A and/or PP2B in adult rat brain extracts dephosphorylated tau in a site-specific manner. Thus, PP2A and PP2B (or closely related phosphatases) may regulate the phosphorylation state of adult tau isoforms in vivo, and the generation of PHF-tau in the AD brain may result from the abnormal inactivation of similar phosphatases.

Alzheimer disease: from abnormal phosphorylation of tau to neurofibrillary degeneration : K. Iqbal, A. del C. Alonso, C.-X. Gong, S. Khatoon, J.-J. Pei, J.Z. Wang and I. Grundke-Iqbal. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 USA

The relationship between Alzheimer's disease (AD) and expression of fetal proteins was examined by: (i) determining the phosphate content of tau prepared from fetal brains (F-tau); (ii) comparing F-tau, tau from normal adult human brains (N-tau) and tau from paired helical filaments in AD brains (PHF-tau) for phosphate content; and (iii) testing the reactivity of F-tau with five antibodies known to recognize PHF-tau. The antibodies have been reported to recognize phosphate dependent epitopes at the carboxy-terminal half of the tau molecule. Our data shows that on the average, F-tau contains 7 mol phosphate/mol protein, which is comparable to the phosphate content of PHF-tau, but is 3–4 times higher than that of N-tau. Immunoblotting shows that all of the tested antibodies reacted with F-tau on immunoblots, indicating that F-tau and PHF-tau are phosphorylated at similar sites. A difference between PHF-tau and F-tau is the state of phosphorylation in the Tau-1 epitope, an epitope reactive with a monoclonal anti-tau antibody, Tau-1. This epitope, which is phosphorylated in all PHF-tau, is phosphorylated only in some of the F-tau. The sharing of phosphorylated sites between F-tau and PHF-tau has also been reported by others in studies with antibodies to different and similar phosphorylated epitopes. Together these observations indicate that the extent and the site of phosphorylation in F-tau and PHF-tau tau are similar. Although hyperphosphorylation of tau proteins may be an important step for PHF formation, the absence of AD type pathology in fetal brains containing hyperphosphorylated tau suggests that the transformation of soluble forms of normal tau to AD type cytoskeletal abnormalities may require the presence of other factors.

The extent of phosphorylation of fetal tau is comparable to that of PHF-tau from Alzheimer paired helical filaments

The relationship between Alzheimer's disease (AD) and expression of fetal proteins was examined by: (i) determining the phosphate content of tau prepared from fetal brains (F-tau); (ii) comparing F-tau, tau from normal adult human brains (N-tau) and tau from paired helical filaments in AD brains (PHF-tau) for phosphate content; and (iii) testing the reactivity of F-tau with five antibodies known to recognize PHF-tau. The antibodies have been reported to recognize phosphate dependent epitopes at the carboxy-terminal half of the tau molecule. Our data shows that on the average, F-tau contains 7 mol phosphate/mol protein, which is comparable to the phosphate content of PHF-tau, but is 3–4 times higher than that of N-tau. Immunoblotting shows that all of the tested antibodies reacted with F-tau on immunoblots, indicating that F-tau and PHF-tau are phosphorylated at similar sites. A difference between PHF-tau and F-tau is the state of phosphorylation in the Tau-1 epitope, an epitope reactive with a monoclonal anti-tau antibody, Tau-1. This epitope, which is phosphorylated in all PHF-tau, is phosphorylated only in some of the F-tau. The sharing of phosphorylated sites between F-tau and PHF-tau has also been reported by others in studies with antibodies to different and similar phosphorylated epitopes. Together these observations indicate that the extent and the site of phosphorylation in F-tau and PHF-tau tau are similar. Although hyperphosphorylation of tau proteins may be an important step for PHF formation, the absence of AD type pathology in fetal brains containing hyperphosphorylated tau suggests that the transformation of soluble forms of normal tau to AD type cytoskeletal abnormalities may require the presence of other factors.

Quantitative 31P MRS of the normal adult human brain. Assessment of interindividual differences and ageing effects.

The characteristics of the 31P MR spectra from a large central volume in the brain of 47 healthy adults (aged 25-85 years) were assessed. Spectral parameters were estimated by means of a time-domain fitting technique. Statistical uncertainties of the estimates were determined by means of the Cramer-Rao theory and minimized by introducing a priori knowledge into the fitting procedure. Age-dependency of the spectral parameters was assessed by means of linear regression. Significant differences between individuals were established for some parameters. A significant age-dependency (p < or = 0.001) of ca 20% over the age range considered was found for the intensity of the phosphocreatine resonance line.

Presence of typical neuronal markers in serially cultured cells from adult human brain

Typical markers for neurons but not for astroglia have been identified in cells cultured from a sample of normal adult human temporal lobe, which was removed to gain access to a glioma. Cells were grown in medium containing growth factors, including fibroblast growth factor and nerve growth factor. The cells grew slowly (doubling time, 18 days) and have been carried as far as passage 8 over 10 months. Both immunoblotting and immunocytochemistry with redundant antibodies demonstrated the presence of neurofilaments (NF-H, NF-M, NF-L), but not glial fibrillary acidic protein (GFAP). Neuron-specific enolase (NSE) was also found. Morphologically, the cultures consisted of a pleiomorphic population of cells with frequent long processes. Cells demonstrating neuronal rather than astroglial markers can be cultured from normal adult human brain.

Epidermal growth factor and its receptor in the developing human nervous system

Recent data suggest that epidermal growth factor and epidermal growth factor receptors (EGF/EGF-R) are present and functional in neurons within the central nervous system. Previously, EGF was detected in developing and mature rat brain and cerebrospinal fluid. Also, EGF-R was documented in discrete locations in normal adult human brain, as well as in senile plaques associated with Alzheimer's disease. Using two polyclonal sera, anti-EGF and anti-EGF-R, in conjunction with immunohistochemical staining, we examined formalin-fixed, paraffin-embedded neural tissues from 10 autopsied, human brains. These specimens were collected from patients who died during various stages of development ranging from 27 weeks of estimated gestational age to 63 years of age. Immunostaining for EGF and EGF-R was detected in hippocampal pyramidal cells, Purkinje cells, large multipolar neurons of the dentate nucleus, anterior horn cells, dorsal root ganglion cells, cells of the dorsal nucleus of Clark, intermediolateral column cells and ependymal cells. Positive binding studies with 125I-EGF confirmed that numerous EGF receptors are unoccupied, assessable, and available for interactions with potential ligands such as EGF and TGFα in developing rat brains. It appears that EGF and/or EGF-R may play a role during maturation and differentiation of the human central nervous system.

Histamine neurons in human hypothalamus: Anatomy in normal and alzheimer diseased brains

The anatomy of histamine-immunoreactive cell bodies in normal adult human brain was examined in detail. In addition, the distribution of these cells in three cases of Alzheimer's disease was compared to the distribution of neurofibrillary tangles. Histamine-immunoreactive cell bodies were confined to the tuberal and posterior hypothalamus, forming the tuberomammillary nuclear complex. Most of the about 64,000 histamine neurons were large and multipolar. They comprised four distinct parts: (i) a major ventral part corresponding to the classical tuberomammillary nucleus, (ii) a medial part including the supramammillary nucleus and part of the posterior hypothalamic area, (iii) a caudal paramammillary part, (iv) a minor lateral part. The parts showed some similarity with the subgroups in rat. In human, as compared to rat, the histamine neurons occupy a larger proportion of the hypothalamus. Numerous neurofibrillary tangles were found in the Alzheimer hypothalami, concentrated in the tuberomammillary area. Most of them were of globular type and extracellular, and only a minority were histamine immunoreactive. They may represent remnants of degenerated tuberomammillary neurons.

Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain

The distribution of endothelin mRNA and immunoreactivity in the human brain was investigated using the technique of in situ hybridization and immunocytochemistry. Cryostat sections from 22 cases of neurologically normal adult human brain, collected 3-7 h post-mortem were hybridized with 35S-labelled complementary (c)RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization with all three cRNA probes revealed labelled neuronal cell bodies in laminae III-VI of the parietal, temporal and frontal cortices. Labelled cells were also seen, scattered throughout the para- and periventricular, supraoptic and lateral hypothalamic nuclei, the caudate nucleus, amygdala, hippocampus, basal nucleus of Meynert, substantia nigra, raphe nuclei, Purkinje cell layer of the cerebellum and in the dorsal motor nuclei of the vagus of the medulla oblongata. The distribution of neurones immunoreactive to endothelin was similar to that of endothelin mRNA, although fewer immunoreactive cells throughout the brain, were noted. Immunoreactive fibres were present mainly in the cortex and hypothalamus, and to a lesser extent in the brain stem. Combined in situ hybridization and immunocytochemistry on the same section revealed the presence of endothelin-1 mRNA and immunoreactivity in the same cortical neuronal cell. Colocalisation studies in the cortex revealed endothelin-1 mRNA and immunoreactivity in a number of cells which also expressed neuropeptide Y mRNA and immunoreactivity. In the hypothalamus and basal nucleus of Meynert endothelin immunoreactivity was colocalised to a subset of neurophysin- and galanin-immunoreactive cell bodies respectively. Endothelin mRNA and immunoreactivity was also seen in some blood vessel endothelial cells. The findings of endothelin mRNAs and immunoreactivity in heterogenous neuronal populations further emphasises the potential role of endothelin as a neuropeptide, probably having diverse actions in the nervous system of man.

Distribution of Neuropeptide Y, C-Terminal Flanking Peptide of NPY and Galanin and Coexistence with Catecholamine in the Locus coeruleus of Normal Human, Alzheimer's Dementia and Parkinson's Disease Brains

The study demonstrates the presence of neuropeptide Y (NPY)-, C-terminal flanking peptide of NPY (C-PON)-, and galanin (GA)-immunoreactive (-i) neurons and axons in the locus coeruleus in normal adult human brain and in brains of patients with senile dementia of the Alzheimer type (SDAT) and Parkinson''s disease (PD) as well as evidence for the coexistence of peptides with catecholamines in individual locus coeruleus neurons. The morphology of C-PON-i neurons is analysed in detail with a computer-assisted program. They are either multipolar neurons with round or multiangular somata, or ''bipolar'' neurons with major dendrites issuing from the two poles of fusiform cell bodies, and represent small- to medium-sized locus coeruleus neurons. In the controls, C-PON-i and NPY-i neuron numbers are highest rostrally, lower in the middle and lowest in the caudal locus coeruleus. GA-i neurons are more frequent caudally. C-PON-i neuron numbers are decreased in old normal adult brains compared to young brains. NPY-i and GA-i neuron numbers are very low in all age groups. The axonal networks are densest rostrally. C-PON-i and NPY-i axons possess larger varicosities and thicker intervaricose segments than GA-i axons. Both the peptidergic neuronal systems and the innervation pattern are detrimentally altered in SDAT and PD, more so in the latter than in the former cases. In SDAT, some C-PON-i locus coeruleus neurons display morphological alterations resembling those encountered in tyrosine hydroxylase (TH)-i neurons in the same cases, with blurred somatic outlines, misshapen cell bodies and foreshortened dendrites. However, the alterations are generally less severe than those of the TH-i neurons and many C-PON-i neurons appear to be entirely normal. &lt;i&gt;Relative to the number of TH-i neurons, the numbers of peptide-i neurons are higher in SDAT than in controls, and often more neurons are located caudally. &lt;/i&gt;Peptide-i axonal networks are less dense, and the remaining C-PON-i and NPY-i axons are tortuous and have larger varicosities than normal. In PD, the changes of C-PON-i neuronal morphology are as severe as in the TH-i neuron population, with rounded cell bodies and loss of dendritic arbors; the peptide-i innervation is reduced. The alterations in the peptide-i systems of the locus coeruleus, especially the increase in the numbers of neurons in SDAT, may be interpreted in terms of a plasticity of the aged brain.

Immunocytochemical characterization of primary glial cell cultures from normal adult human brain.

Primary cultures were established from autopsy or biopsy samples of normal adult human brain and characterized by immunocytochemical techniques. Initially, macrophages were the predominant cell type adhering to the substratum, but as their number fell that of glial cells increased. Oligodendrocytes comprised 30% of the glial population in white matter cultures, and their perikarya and elongated processes were immunostained with antibodies directed against galactocerebroside and four myelin proteins. In white and grey matter cultures, process-bearing astrocytes and small numbers of polygonal astrocytes were stained with antibodies against glial fibrillary acidic protein and glutamine synthetase. Fibroblasts started to appear at 3 weeks and proliferated to form a monolayer beneath glial cells by 5 weeks. Glia began to die in the 6th week. These primary cell cultures of white or grey matter can be used to study the properties of glial cells from normal or pathological adult human brain.

Absence of mutation in the β-amyloid cDNAs cloned from the brains of three patients with sporadic Alzheimer's disease

Using an oligonucleotide probe, we isolated cDNA clones corresponding to the precursor of the β-amyloid peptide (BAP) from brain libraries of 3 patients with sporadic Alzheimer's disease (AD). DNA sequencing showed that the largest cDNA clone encompasses 83% of the open reading frame proposed by Kang et al. to encode the BAP precursor (APP). cDNA clones from each of the 3 AD brain libraries were identical to the sequence of the APP-cDNAs cloned from normal adult human and fetal brain. An antisense-radiolabeled RNA copy of one of the AD clones detected a pattern of 3 gene transcripts measuring 3.5, 3.2 and 1.6 kilobases (kb) in both normal and AD brain RNAs. These data suggest that there are no mutations in or about the 42 amino acid (aa) sequence of BAP and that the accumulation of amyloid consistently found in AD may result from altered post-translational processing of APP.

A human brain glycoprotein related to the mouse cell adhesion molecule L1.

We have employed monoclonal antibody 5G3, an antibody used to label human tumor cells of neural origin (Mujoo, K., Spiro, R.C., and Reisfeld, R. A. (1986) J. Biol. Chem. 261, 10299-10305), to isolate and characterize a large glycoprotein from normal adult human brain. This protein was compared to mouse L1 (Rathjen, F. G., and Schachner, M. (1984) EMBO J. 3, 1-10), a neural cell surface glycoprotein implicated predominantly in neurite-neurite interactions. On the basis of the following results the 5G3 antigen is considered to be the human homologue of mouse L1. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both proteins share similar molecular masses of their carbohydrate-depleted or undepleted components. In tryptic fingerprint analyses of the iodinated L1 and 5G3 components, 65% of the resolved peptides comigrated. Comparison of NH2-terminal amino acid sequences revealed a high degree of homology between human 5G3 and mouse L1, with 11 of 15 residues being identical. Furthermore, polyclonal antibodies to human 5G3 antigen were found to be cross-reactive with mouse L1 antigen and vice versa. All components of 5G3 and L1 antigens show considerable charge heterogeneity with partial overlapping of regions in isoelectric focusing followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These findings provide a basis for studying the role of the human L1 homologue in human diseases.

Expression of Ia antigens on the surface of human oligodendrocytes and astrocytes in culture

Oligodendrocytes and astrocytes were isolated from normal adult human brains 3–15 h postmortem using a Percoll density gradient centrifugation and were cultured for 10–135 days. The presence of HLA-DR(Ia) antigens on the surface of these human oligodendrocytes and astrocytes was studied using double immunofluorescence procedures. Only half of separate culture series (6/12 donors) contained HLA-DR-positive oligodendrocytes, while all of the culture series (12/12 donors) revealed HLA-DR positive astrocytes. Among the HLA-DR-positive cultures, 4–16% of galactocerebroside-positive oligodendrocytes and 9–24% of GFAP-positive astrocytes were found to immunoreact with HLA-DR antibody. The presence of Ia antigens on the surface of certain populations of oligodendrocytes and astrocytes may be important in the induction of an immune response to these cells.

The determination of glial fibrillary acidic protein for the diagnosis and histogenetic study of central nervous system tumors: a study of 152 cases.

Glial fibrillary acidic protein (GFAP) was purified from human spinal cord and cerebral white matter. GFAP was localized by an immuno-peroxidase method in normal adult and fetal human brains, rat brains, and 152 central nervous system (CNS) tumors. GFAP was found in reactive and normal astrocytes, immature cells of fetal brain at the 18th to 21st gestational weeks, and normal rat astrocytes. This GFAP staining was quite specific for glial tumors, including astrocytomas, glioblastomas, astroblastomas, and ependymomas. GFAP-positive cells were also found in oligodendrogliomas and choroid plexus papillomas, and they were interpreted as being astroglial or ependymal differentiations. Stromal cells in cerebellar hemangioblastomas were negative. However, engulfed astrocytes were found at the periphery of such tumors and often adjacent to the proliferate blood vessels. In meningiomas, neurinomas, metastatic carcinomas, pituitary adenomas and other non-glial tumors, GFAP-positive cells were not identified.

Distribution of catecholamine-containing neurons in the normal human hypothalamus

We have studied the distribution of catecholamine-containing neurons in the hypothalamus of 8 normal adult human brains, using Schmorl's stain for melanin and immunohistochemical staining for tyrosine hydroxylase (TH). TH immunoreactive perikarya were found in the wall of the third ventricle, in the areas in which dopaminergic neuroendocrine neurons are found in other primate species. Many of these neurons contained melanin pigment, and the percentage increased with age. Other melanin-pigmented neurons in the same distribution did not stain for TH, suggesting that postmortem TH immunostaining may not be sufficiently sensitive to visualize all catecholaminergic neurons. A separate group of larger TH-positive perikarya was seen in the lateral hypothalamic area. These may correspond to the incerto-hypothalamic dopamine neurons in other primate species. Only rare melanin-pigmented neurons were seen in this cell group, even at 66 years of age. Our data indicate that the hypothalamic neuroendocrine dopamine neurons in the human brain are distributed in a pattern similar to that in other primate species, and that both postmortem tyrosine hydroxylase and melanin staining provide an incomplete but representative sampling of the periventricular-arcuate cell group.