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Kinetic properties of the 5 alpha-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain.

The 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5 alpha-reductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5 alpha-reductase has a higher activity in immature animals. This study was performed in order to verify whether the differences in the 5 alpha-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60-90-day-old), immature (23-day-old), and aged (greater than 20-month-old) male rats. The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 +/- 0.2, 2.72 +/- 0.73 and 3.83 +/- 0.49 microM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 +/- 5.54), in the white matter (19.57 +/- 2.36) and in the cerebral cortex (6.47 +/- 1.03 ng/h/mg protein) of adult animals have been found to be consistently different. Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 +/- 0.11 and 3.39 +/- 0.75 microM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 +/- 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 +/- 5.54); a Vmax (34.31 +/- 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

On the white matter lesions of the Creutzfeldt-Jakob disease. Can a new subentity be recognized in man?

One case of CJD with severe involvement of the white matter is discussed. The patient was admitted after a 3-month clinical course with rapidly increasing mental deterioration, coma vigil-like state, myoclonic twitching of the limbs and of the facial muscles. The EEG showed the typical features of CJD. The first CT scan, performed 3 months after onset, revealed only a mild cortical and subcortical atrophy of the brain. The second CT scan, 12 months later, showed a considerable cortical and subcortical atrophy of the brain. The patient died 18 months after onset. Neuropathological examination showed a severe degeneration in the gray matter, with spongiosis, loss of neurones and hypertrophic glial reaction. The white matter was also involved with severe spongiosis, demyelination and hypertrophic glial proliferation. The case is discussed in relation to the data in the literature. It is argued that cases of CJD with severe involvement of the white matter should be classified as a new neuropathological subentity of CJD.

Atrophy↗

Spongiform encephalopathy with extensive involvement of white matter.

We report a proven case of CJD with prolonged clinical course and white matter involvement which consisted of severe, widespread myelin damage in the forebrain and cerebellum but with sparing of the internal capsule. Histologically, there was status spongiosus of the involved white matter with axonal loss, proliferation of hypertrophic astrocytes and scattered and perivascular foamy macrophages. White matter lesions have not been considered to be a significant feature of CJD. In the last few years, however, a few cases have been described with prominent degeneration of cerebral white matter. We believe that our findings corroborate the existence of an entity that at present may only be defined as spongiform panencephalopathy.

Adult↗

Selective elimination of transient corticospinal projections in the rat cervical spinal cord gray matter.

In the present paper a description is given of the development of the rat corticospinal tract (CST) in the lower cervical spinal cord. This area contains, among other cells, the motoneurons innervating the distal forelimb muscles. HRP gels were implanted in the sensorimotor cortex of Wistar rats varying in age from postnatal day 0 (P0) to P60. After a survival period of 48 h, the rats were transcardially perfused, the spinal cords transversely sectioned at 30 microns and the sections reacted for HRP. Labelled CST axons in the dorsal funiculus were first detected at P2, and after a delay of 2 days the first fibres were found in the adjacent gray matter (P4). More labelled fibres were gradually added until maximal number and extension was reached at P10. By then the entire gray matter and large parts of the white matter were covered by labelled CST axons. From P10 onwards, the number of labelled CST fibres as well as their extension decreased. In the adult rat, some areas such as the lateral part of the ventral and dorsal horn and large parts of the ventral and lateral white matter ultimately became devoid of labelled CST axons. It is concluded that a massive overshoot occurs during the development of the terminal field of the rat CST. The results are discussed in conjunction with our previous findings on the development of the motoneurons innervating the rat distal forelimb muscles. The concurrent selective elimination of both CST axons and motoneuron dendrites is suggested to be correlated with progressively more mature, coordinated movements and with high digital skills especially.

Aging↗

Distribution of neuropeptide Y immunoreactivity in human visual cortex and underlying white matter.

Immunocytochemical techniques have been used to study neuropeptide Y (NPY) distribution in the human visual cortex (Brodman's areas 17, 18 and 19) NPY cell bodies belong mostly to inhibitory (multipolar and bitufted) but also to excitatory (bipolar and some pyramidal) neuronal types. Their distribution is similar in the three cortical areas studied: 20 to 40% of the NPY perikarya are located in the cortical gray matter, mostly in the deep layers, while the remaining 60 to 80% are located in the underlying white matter. Immunoreactive NPY processes form a rich network of intersecting fibers throughout the entire visual cortex. A superficial plexus (layers I and II) and a deep plexus (deep layer V and layer VI) of NPY fibers are present in areas 17, 18 and 19. In area 17, an additional well developed plexus is present in layers IVb and IVc. These plexuses receive branches from long parallel fibers arising from deep cortical layers or underlying white matter and terminating in superficial layers. Local or extrinsic NPY terminals wind around vessels in the cortex as well as in the white matter, and either penetrate them or form clusters of club endings on their walls. Our results suggest a role for NPY in human visual circuitry and in cortical blood flow regulation.

Aged↗

Effect of fluoride on pH, organic matter and solubility of elements in soils.

The effect of NaF addition on pH, organic matter and the solubilities of fifteen elements was investigated on twenty-eight surface soil samples. Four concentrations of NaF were added: 0, 10(-2.7), 10(-1.7) and 10(-1.0)m F in solution. Addition of NaF increased the pH and the solubility of organic matter for all soils. The magnitude of these increases was higher for acid than for alkaline soils. Aluminum, Fe and Ca showed the greatest increases in solubility while Mg, K, Mn and P showed intermediate increases. The elements Cd, Cr, Ni, Cu, Zn, B, Mo and Ba showed only slight increases in solubility. Another experiment was conducted to test whether the effects of NaF on pH, organic matter and the solubilities of various elements were due to F or Na. Four levels of NaCl similar to those for NaF were added to three acid and two alkaline soils. The results confirmed the effects of F on soil pH, organic matter and the solubilities of all elements investigated except those of K, Ca and Mg. Addition of Na as NaF resulted in release of K, Ca and Mg from the exchange sites on solid surfaces into solution.

Journal Article↗

Spatial and seasonal variation of major and trace elements in settling particulate matter in an estuarine-like archipelago area in the Northern Baltic proper.

This study describes the spatial and the seasonal variation of flux and concentration of 11 metals (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Zn), organic matter and C and N in settling particulate matter collected with sediment traps during seven interconnective, continuous periods totalling 15 months. Ten sediment traps were placed out along the metropolis-affected fresh water outflow of Lake Mälaren, out through a non-tidal estuarine-like region with a low salt content, through the Stockholm archipelago to the Baltic. The metal concentrations of the particles were analysed with AAS using the flame technique and the amounts of C and N were determined with elemental analysis (CHN). The flux of particulate matter and of all metals decreased rapidly outwards in a gradient from the innermost stations. The distribution and composition of the particles were dominated by variations in the runoff from Lake Mälaren and by the seasonal dependence on primary production. However, they were also influenced locally by the supply of nutrients via water treatment plant effluents and probably by the special sedimentation conditions in the mixing zones and by resuspension. The concentrations of Cu, Hg, Pb and Cd in the interior of the area under investigation were the most elevated of the elements and decreased markedly further out in the archipelago, indicating local anthropogenic input. Zn, Cr and Fe also showed signs of supply from the urbanized environment. The flux of most of the metals studied displayed both spatial and seasonal correlation with the weight (TPM) of the material, whereas seasonal variation of Cd was correlated to its volume (TPV) and concentration of organic matter (POM, PC and PN).

Journal Article↗

Insulin-like growth factor-I receptor densities in human frontal cortex and white matter during aging, in Alzheimer's disease, and in Huntington's disease.

Using quantitative autoradiography we have investigated insulin-like growth factor (IGF)-I receptors in postmortem-obtained frontal cortex and white matter from 39 individuals without neurological disease, ranging in age from 0 to 95 years, and from 5 patients with Huntington's disease and 4 with Alzheimer's disease. IGF-I receptor densities in white matter were significantly higher in neonates than in adults; during adult life there was no further decline. The higher density of IGF-I receptors in white matter of neonates most likely reflects extensive formation of myelin. There was no significant decrease in IGF-I receptor densities in the cortical mantle with age, suggesting that the cells containing IGF-I receptors in frontal cortex are maintained during the entire life-span. There were no significant alterations in IGF-I receptor densities in frontal cortex and white matter from patients with Huntington's disease and Alzheimer's disease compared with controls from the same age groups.

Adolescent↗

Influences of central gray matter stimulation on thalamic neuron responses to high- and low-threshold stimulation of trigeminal nerve structures.

Responses of the thalamic non-specific medial nuclei and relay ventral posteromedial nucleus neurons evoked by stimulation of the teeth pulp of A alpha and A sigma fibers of infraorbital nerve and caudal nucleus of the spinal trigeminal tract were studied in cats under thiopental-chloralose anesthesia. Three groups of neurons were revealed: low-threshold, high-threshold and convergent. In medial nuclei, 29% of neurons formed the low-threshold group, 12% made up the high-threshold group and 59% were convergent. In the ventral posteromedial nucleus 47% of neurons formed the low-threshold group, 4% made up the high-threshold group and 49% were convergent. Ninety per cent of the medial nuclei neurons and 79% of the ventral posteromedial nucleus neurons responded to stimulation of the caudal nucleus spinal trigeminal tract. The conditioning central gray matter stimulation could suppress responses of low-threshold, high-threshold and convergent neuron groups. In medial nuclei 100% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 86% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve stimulation were also completely suppressed. In the ventral posteromedial nucleus 40% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 26.4% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve were completely suppressed. Conditioning stimulation of the central gray matter suppressed responses evoked by stimulation of the caudal nucleus spinal trigeminal tract and in the most part neurons of the medial nuclei and neuron responses of the ventral posteromedial nucleus. The inhibitory influence of central gray matter stimulation on neuronal responses evoked by stimulation of the caudal nucleus spinal trigeminal tract shows that the central gray matter had a direct influence on the activity of thalamic neurons.

Animals↗

Influence of the dorsal and median raphe nuclei on neurons in the periaqueductal gray matter: role of 5-hydroxytryptamine.

In rats anaesthetized with urethane, selective activation of neuronal perikarya in the dorsal raphe nucleus evoked inhibitory (n = 17) and excitatory (n = 10) responses in single neurons recorded in the dorsolateral and lateral sectors of the periaqueductal gray matter and in the adjacent tegmental area. A further 11 cells showed biphasic inhibitory/excitatory responses. Ongoing activity of > 85% of the cells was inhibited by iontophoretic application of 5-hydroxytryptamine (1-70 nA). The duration of the inhibitory response evoked from the dorsal raphe nucleus was increased by 66-75% during iontophoretic application (3-10 nA) of the 5-hydroxytryptamine (serotonin) reuptake blocker paroxetine (five of six cells). In contrast, excitatory responses evoked from the dorsal raphe nucleus were either reduced (n = 3) or replaced by inhibitory responses (n = 2) in the presence of paroxetine. Paroxetine also produced a reduction in baseline firing and potentiated the responses of neurons to iontophoretically applied 5-hydroxytryptamine. Stimulation in the median raphe nucleus did not produce any significant changes in the activity of five neurons tested in the periaqueductal gray matter. It is suggested that the inhibitory influence of the dorsal raphe nucleus on cells in the dorsal half of the periaqueductal gray matter is mediated by 5-hydroxytryptamine. This projection may be involved in modulating the level of excitability of neurons in the midbrain aversive system which integrate defence behaviour. In addition, there appears to be a non-serotonergic excitatory projection from the dorsal raphe nucleus to the periaqueductal gray matter. The functional role of this projection remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the "invisible" lesion load.

Prolonged T1 and/or T2 relaxation times (RT) in the normal appearing white matter (NAWM) of patients with multiple sclerosis (MS) have been attributed either to a diffuse abnormality, or to "small lesions" undetected by visual inspection of conventional MR images. In a comparison of brain slices from five MS patients and five healthy control subjects, we have confirmed that the average T1 and T2 RTs obtained from NAWM in patients with MS are significantly prolonged (p < .04). Quantitative pixel-by-pixel mapping shows that this overall prolongation is due to the averaging of RTs from two subfractions of NAWM. In all patients a proportion (average 54% for T1 and 63% for T2) of the total white matter pixel sample from each MR brain slice had RT values indistinguishable from those found in the white matter of matched healthy control subjects (i.e., "normal normal appearing white matter," NNAWM). Scattered throughout the NAWM were multiple small areas, often of only one or two pixels, with abnormal RT values. These lesions, which were revealed only by pixel-by-pixel mapping of RT, made up a significant proportion (average 47% for T1 or 57% for T2 estimates) of the total (visible plus "invisible") lesion load per slice, and of the NAWM (average 36% for T1, 27% for T2), with wide interpatient variability. Further studies of these minute lesions are required to determine their total volume in the brain, their precise nature, evolution and relevance to the functional deficit in MS.

Brain↗

Linear nevus sebaceous syndrome: megalencephaly and heterotopic gray matter.

A 3-month-old white male with linear nevus sebaceous syndrome (LNSS), facial deformities, brain malformations, and cortical blindness is presented. Facial deformities included left ear hypertrophy and a left-sided hamartomatous neck mass. Magnetic resonance imaging suggested that a central nervous system (CNS) abnormality, involving gray and white matter, should be linked with LNSS. Magnetic resonance imaging was more useful than computed tomography in demonstrating the full spectrum of CNS anomalies, including unilateral lissencephaly, a paucity of white matter, excessive and heterotopic gray matter, apparent left schizencephaly, and unilateral left colpocephaly (dilation of atrium and posterior horn of lateral ventricle). Postmortem examination revealed left hemisphere megalencephaly with a dilated posterior horn of the lateral ventricle. The impressive gray matter heterotopias likely were the source of the patient's seizures and perhaps the ultimate cause of death. Megalencephaly and other deviations of neuronal migration should be considered as a dramatic component of LNSS.

Astrocytes↗

Posterior superior temporal gyrus in schizophrenia: grey matter changes and clinical correlates.

We report an MRI morphometric study of the posterior segment of the superior temporal gyrus (STG) in twenty young male schizophrenics and their individually matched normal controls. In particular the more posterior segment of STG was examined, since it has been identified as the approximate site of Wernicke's language area and is a marker for the planum temporale, a region believed to be abnormal in schizophrenia. Total volumes and grey and white matter volumes were measured in middle and posterior STG in each hemisphere. STG grey matter volumes and percentages were significantly reduced bilaterally in both regions in schizophrenic subjects. No significant differences between patients and controls were noted in STG white matter volumes. A significant correlation was detected between delusion scores in schizophrenics and the total volume of the left dominant posterior STG. Replicating the findings of a recent study (Shenton et al., 1992), we found an inverse correlation between thought disorder scores and grey matter reduction in the left posterior STG in schizophrenia.

Adult↗

Duration of labor and risk of cerebral white-matter damage in very preterm infants who are delivered with intrauterine infection.

OBJECTIVE: The purpose of this study was to assess whether the duration of labor has any effect on the occurrence of cerebral white-matter damage in very preterm infants who are delivered in the presence of intrauterine infection. STUDY DESIGN: From a cohort of infants who were born spontaneously at <32 weeks of gestation for whom placental information was available and who survived 7 days from birth, 126 infants had clinical, laboratory, or histologic evidence of intrauterine infection. Among them, variables were compared between those infants with white-matter damage (defined as intraventricular hemorrhage grade 3 plus, periventricular leukomalacia, or ventriculomegaly not associated with hydrocephaly [n = 13]) and those infants without it (n = 113). Comparisons were made with t test, chi-squared test, and survival analysis; a probability value of <.05 was considered significant. RESULTS: There were no differences between the 2 groups in gestational age at delivery and rates of labor or cesarean delivery. Duration of active labor (66 +/- 45 minutes vs 88 +/- 75 minutes; P =.49) and of clinical chorioamnionitis (310 +/- 186 minutes vs 529 +/- 544 minutes; P =.44) were similar in cases with and without neonatal white-matter damage. CONCLUSION: In 126 infants who were born at <32 weeks of gestation with intrauterine infection, we found no correlation between the duration of labor or clinical chorioamnionitis and neonatal white-matter damage.

Adult↗

Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses.

BACKGROUND: Neurons in the basal ganglia are connected to areas of prefrontal cerebral cortex involved in higher cognitive functions, and these connections occur primarily via the thalamus. In patients with bipolar disorder, regardless of age, neuroimaging studies have consistently reported an increased number of white matter hyperintensities, indicating possible alterations in striatum-thalamus and thalamus-prefrontal cortex connections. METHODS: In the current study, we acquired high-resolution magnetic resonance imaging (MRI) and diffusion tensor (DT) scans of 40 patients with bipolar spectrum (BPS) illnesses (bipolar type I = 17, bipolar type II = 7, cyclothymia = 16) and 36 sex- and age-matched control subjects. Two researchers, without knowledge of diagnosis, outlined the caudate, putamen, and thalamus on contiguous axial MRI slices. We measured the volumes of the basal ganglia, thalamus, and gray/white matter of the frontal cortex. RESULTS: Bipolar spectrum patients as a single group did not differ from control subjects in thalamus and the basal ganglia volumes, but the cyclothymia patients had reductions in the volumes of putamen and the thalamus compared with control subjects. The BPS patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter. CONCLUSIONS: Our findings indicate that BPS patients may have distinct anatomical alterations in brain structures involved in the regulation of mood and cognition, as well as alterations in these structures' connection to related brain areas.

Adult↗

Changes in gray matter volume in patients with bipolar disorder.

BACKGROUND: Several lines of evidence suggest the presence of neurofunctional abnormalities in patients with bipolar disorder. These functional abnormalities may stem from structural pathology in these or connected brain regions. Previous studies have generally used a region of interest (ROI) approach to study morphologic changes in bipolar disorder with inconsistent findings among research groups, which may reflect differences in how ROIs are defined. Voxel based morphometry (VBM) allows a more exploratory analysis without the necessity for predefined anatomic boundaries. In this study we utilized VBM to compare gray matter volume between groups of bipolar and healthy subjects. METHODS: Thirty-two patients with bipolar disorder and 27 healthy subjects participated in structural magnetic resonance imaging (MRI) scans. MRI images were segmented, normalized to a standard stereotactic space, and compared on a voxel-by-voxel basis using statistical parametric mapping. RESULTS: Bipolar subjects showed increased gray matter in several regions including portions of anterior cingulate, ventral prefrontal cortex, fusiform gyrus and parts of the primary and supplementary motor cortex. Bipolar subjects showed decreased gray matter volume in superior parietal lobule. CONCLUSIONS: These data support suggestions that neurofunctional deficits are related to structural brain abnormalities in patients with bipolar disorder. The increased gray matter observed in several regions suggests that some affected areas may demonstrate volumetric expansion, at least in some patient populations.

Adult↗

Immunohistochemical analysis of subcortical white matter astroglia of infant and adult primate brains, with a note on resident neurons.

An immunohistochemical analysis of brain subcortical white matter astroglia from human (infant, adult) and adult monkey (Cebus apella, Macaca nemestrina) cases without any known neurological disease, is described. Expression of synaptic vesicle-associated proteins, excitatory amino acid transporters (EAAT1 and EAAT2) and GABAA Ralpha2 receptor produced coarse punctate labeling in human adult white matter astrocytes. A finer, generalized, punctate labeling was observed in human infants and adult C. apella monkeys. Labeling of neuronal somata and processes with microtubule-associated proteins (MAP2a-c) and neuron nuclear (NeuN) antibodies, was also observed in subcortical white matter of humans and monkeys. Results suggest competence of subcortical white matter astroglia of the primate brain to participate in various transmitter regulatory pathways. It is also proposed that, collectively with resident neurons, they may exert some role in affecting the transfer of information that takes place through the various associational and projecting fiber systems coursing through this brain compartment.

Aged↗

White matter lesions in Fabry disease occur in 'prior' selectively hypometabolic and hyperperfused brain regions.

Fabry disease is an X-linked disorder associated with early onset stroke. We previously found a significantly elevated cerebral blood flow (CBF) in patients with Fabry disease. We set to determine whether elevated resting CBF in Fabry disease is primarily a cerebrovascular abnormality or is secondary to enhanced neuronal metabolism. The relationship of cerebral metabolism and blood flow to Fabry leukoencephalopathy was also investigated. We measured the global and regional cerebral metabolic rate of glucose using 18-fluoro-deoxyglucose (FDG) and PET in 16 patients with Fabry disease (7 patients with leukoaraiotic lesions and 9 without) and in 7 control subjects. MRI fluid attenuated inversion recovery (FLAIR) studies were also performed in the patient and control groups. All control subjects had normal MRI FLAIR studies with no high-signal deep white matter lesions (WML). Patients were partitioned into FLAIR lesion and non-FLAIR lesion groups. We found no evidence of cerebral glucose hypermetabolism in Fabry disease. On the contrary, significantly decreased regional cerebral glucose metabolism (rCMRGlu) was found particularly in the deep white matter in the Fabry non-lesion group and exacerbated in the lesion group. Lesion-susceptible regions were relatively hyperperfused in non-lesion patients compared to the control group. We conclude that the elevated rCBF and decreased white matter rCMRGlu indicates a dissociation between metabolism and blood flow suggesting chronic deep white matter metabolic insufficiency.

Adult↗