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PubMed1986

A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study.

In cases of Alzheimer's presenile and senile dementia, Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT), respectively, we have observed, in addition to the gray matter degeneration, a lesion that has the character of an incomplete infarction confined to the white matter. It is encountered in 60% of both groups, with mild changes in two thirds and moderate or severe changes in one third. It involves the deep white matter symmetrically, tapering off toward the cortex. It is characterized by partial loss of myelin, axons, and oligodendroglial cells; mild reactive astrocytic gliosis; and sparsely distributed macrophages as well as stenosis resulting from hyaline fibrosis of arterioles and smaller vessels. No complete or cavitating infarctions and no hypertensive vascular changes were observed. The white matter changes are thought to be due to hypoperfusion of the concerned white matter territories since, in addition to the white matter hyaline vascular stenosis, these cases show signs of cardiovascular disease, usually with hypotension. The white matter disorder also occurs independent of the gray matter process of AD and SDAT and may be seen as the sole brain lesion in non-AD subjects. Its occurrence is thus neither regularly related to the severity nor to the regional appearance and accentuation of the cortical Alzheimer process and is thus not likely to be just the result of a wallerian degeneration. Histologically it is similar in several respects to Binswanger's disease, although with some distinct differences. It is thus related to the cerebrovascular group of disorders in addition to AD and SDAT. In view of its frequency and severity, this white matter lesion is important to define, to diagnose, and ultimately to prevent or cure.

Aged↗
PubMed2001

MRI white matter hyperintensities, (1)H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases.

UNLABELLED: BACKGROUND AND OBJECTIVES Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lesions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms. METHOD: Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (< 50 years) group (20 patients; mean age, 62.7 +/- 6.7) and late-onset (> or =50 years) group (27 patients; mean age, 65.6 +/- 5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy ((1)H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted. RESULTS: The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions. CONCLUSION: These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The (1)H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment.

Aged↗
PubMed1994

Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T.

Using a 4.1T whole body system, we have acquired 1H spectroscopic imaging (SI) data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to estimate differences in cerebral metabolites of human gray and white matter. To evaluate the origin of an increased CR/NA and CH/NA ratios in gray matter relative to white matter, we measured the T1 and T2 of CR, NA, and CH in gray and white matter using moderate resolution SI imaging. In white matter the T2s of NA, CR, and CH were 233 +/- 27, 141 +/- 18, and 167 +/- 20 ms, respectively, and 227 +/- 27, 140 +/- 16, and 189 +/- 25 ms in gray matter. The T1 values for NA, CR, and CH were 1267 +/- 141, 1487 +/- 146, and 1111 +/- 136 ms in gray matter and 1260 +/- 154, 1429 +/- 233, and 1074 +/- 146 ms in white matter. After correcting for T1 and T2 losses, creatine content was significantly lower in white matter than gray (P < 0.01, t-test), with a white/gray content ratio of 0.8, in agreement with biopsy and in vivo measurements at 1.5 and 2.0T.

Aspartic Acid↗
PubMed1995

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia.

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.

Adult↗
PubMed1994

Bundles of amyloid precursor protein-immunoreactive axons in human cerebrovascular white matter lesions.

Cerebral white matter lesions commonly observed in Binswanger's disease, multi-infarct encephalopathy and elderly people are neuropathologically characterized by diffuse incomplete demyelination and considered to be ischemic in nature. Arteriolosclerosis in the white matter is a common feature in these white matter lesions. To investigate a possible alteration of the distribution of amyloid precursor protein (APP), chromogranin A (CgA) and synaptophysin (Syn) in such white matter lesions, we examined 15 cases with white matter lesions and 5 without white matter lesions. Many bundles of axons with APP-like immunoreactivity (LI) were observed particularly in mild white matter lesions. Such bundles of axons showed similar but less intense CgA-LI and Syn-LI. They appeared to occur in areas with many ameboid or ramified microglia labeled with anti-leukocyte common antigen and few astrocytes labeled with anti-glial fibrillary acidic protein. In the center of moderate of severe white matter lesions bundles of axons with APP-LI were never observed. Since APP, CgA and Syn undergo fast axonal transport, and since following ischemic insults to central nervous system microglial reaction occurs earlier than astroglial changes, our results suggest that axonal damage, which induces disturbance of fast axonal transport, can occur even in the early stage of white matter lesions.

Aged↗
PubMed1999

Predicting starling chick carcass PCB concentrations from PCB concentrations in ingested animal matter.

Preremediation studies at Crab Orchard National Wildlife Refuge (CONWR) revealed statistically significant accumulations of polychlorinated biphenyls (PCBs) and effects in starling chicks (Sturnus vulgaris) from contaminated sites, including decreased nest attentiveness, decreased fledging success, and an increase in chick mortality. Although the expected route of exposure for starling chicks is thought to be via diet, this has not previously been documented at CONWR. The purpose of this study was to develop an equation to predict starling chick carcass PCB concentrations from PCB concentrations in ingested animal matter. During 1995 and 1996, stomach contents from 14 and 22 starling chicks collected from contaminated and reference sites, respectively, were evaluated. Animal, plant, and mineral matter in the stomach contents were separated and animal matter from stomachs of individuals from the same nest were combined, dried, and percent dry weight calculated. Composite samples of animal matter were then analyzed for the presence of PCBs (Aroclor 1254). Stomach contents were primarily composed of animal matter (76%), and the percent animal matter in the stomachs did not differ significantly among locations (range = 38.4% to 100%). The mean PCB concentration in composite samples of animal matter from stomachs of chicks collected from contaminated sites (1.82 +/- 1.17 mg/kg) was significantly greater than the concentrations in composite samples from two reference locations (<0. 24 mg/kg). PCB concentrations in stomach contents were correlated (Pearson correlation coefficient = 0.91, p < 0.005) with concentrations in carcasses of chicks from which the stomachs had been collected. The regression Y = 6.19 x X(1,398), where Y = starling chick carcass PCB concentration and X = starling stomach animal matter PCB concentration, indicated that PCB concentrations in consumed animal matter accounted for 82% of the variability in starling carcass concentrations.http://link.springer-ny. com/link/service/journals/00244/bibs/37n4p548.html</++ +HEA

Animals↗
PubMed2005

Quantitative analysis of the corpus callosum in children with cerebral palsy and developmental delay: correlation with cerebral white matter volume.

BACKGROUND: The direct quantitative correlation between thickness of the corpus callosum and volume of cerebral white matter in children with cerebral palsy and developmental delay has not been demonstrated. OBJECTIVE: This study was conducted to quantitatively correlate the thickness of the corpus callosum with the volume of cerebral white matter in children with cerebral palsy and developmental delay. MATERIAL AND METHODS: A clinical database of 70 children with cerebral palsy and developmental delay was established with children between the ages of 1 and 5 years. These children also demonstrated abnormal periventricular T2 hyperintensities associated with and without ventriculomegaly. Mid-sagittal T1-weighted images were used to measure the thickness (genu, mid-body, and splenium) and length of the corpus callosum. Volumes of interest were digitized based on gray-scale densities to define the hemispheric cerebral white matter on axial T2-weighted and FLAIR images. The thickness of the mid-body of the corpus callosum was correlated with cerebral white matter volume. Subgroup analysis was also performed to examine the relationship of this correlation with both gestational age and neuromotor outcome. Statistical analysis was performed using analysis of variance and Pearson correlation coefficients. RESULTS: There was a positive correlation between the thickness of the mid-body of the corpus callosum and the volume of cerebral white matter across all children studied (R=0.665, P=0.0001). This correlation was not dependent on gestational age. The thickness of the mid-body of the corpus callosum was decreased in the spastic diplegia group compared to the two other groups (hypotonia and developmental delay only; P<0.0001). Within each neuromotor subgroup, there was a positive correlation between thickness of the mid-body of the corpus callosum and volume of the cerebral white matter. CONCLUSION: The thickness of the mid-body of the corpus callosum positively correlates with volume of cerebral white matter in children with cerebral palsy and developmental delay, regardless of gestational age or neuromotor outcome. Assessment of the thickness of the corpus callosum might help in estimating the extent of the loss of volume of cerebral white matter in children with a broad spectrum of periventricular white matter injury.

Agenesis of Corpus Callosum↗
PubMed2001

Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study.

Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cysts is a neurodegenerative disorder clinically characterized by megalencephaly with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent single-voxel proton MR spectroscopy studies have shown mild metabolic abnormalities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (1H-MRSI) study on 2 new, unrelated patients with this rare disorder. 1H-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneous decreases in all normally detected metabolites with significant widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemispheres. Metabolic abnormalities were milder in the frontal white matter and more severe in the posterior white matter. The 1H-MRSI pattern of the gray matter was normal in both patients. In one patient, a subsequent 1H-MRSI examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine in the white matter. We conclude that severe metabolic abnormalities can be found in the white matter of VML patients. This suggests that, despite the apparently mild clinical course, a severe neurodegenerative process may occur in the white matter of these patients.

Adolescent↗
PubMed1982

Somatostatin: localization and distribution in the cortex and the subcortical white matter of human brain.

Examination of the cortex and the subcortical white matter by use of an immunocytochemical technique--the per oxidase anti-per oxidase method--shows that somatostatin is located in a widespread neuron system with cell bodies localized in both the cortex and the subcortical white matter of the human brain. In the cortex, the somatostatin cell bodies and fibers are found in all layers, but the fibers are especially numerous in layer I located tangentially to the brain surface. The fibers are very long and subdivide into many branches which form a network of pathways in the deeper cortical layers. There are numerous varicosities along the fibers and they come into close contact with other non-immunoreactive neuronal cells. The somatostatin cells located in the white matter are larger than the somatostatin cells in gray matter. They are giant cells with a size ranging from 50 to 120 micrometers. The fibers from these cells are varicose and can be followed both rostrally into the cortical gray matter and caudally in the subcortical white matter. The localization and the morphology of the somatostatin neurons in the cortex and the subcortical white matter indicate that somatostatin may be able to exert sustained influence in various brain areas and thereby modulate integrative and/or specific functions, not only via connection in the gray matter but also by influencing the neuronal circuits passing through the subcortical white matter.

Brain↗
PubMed1990

Organization of cortical afferent and efferent pathways in the white matter of the rat visual system.

Fibers forming reciprocal connections between the dorsal lateral geniculate nucleus and primary visual cortex run in separate tracts in the white matter. The corticofugal fibers are organized into bundles which project through the coronal plane at an oblique angle. We have examined the organization of corticofugal fiber tracts within the white matter of the rat using cortical slices which encompassed the predicted trajectory of these fiber bundles. Field potentials were evoked in layer VI of visual cortex by focal stimulation of subcortical white matter using microbipolar electrodes. Two major responses were elicited: a short-latency and a longer-latency response. The short-latency response was elicited in the superficial strata of white matter with proximal stimulation sites and was obtained in deeper strata for more distant, lateral sites. The longer-latency response was associated with superficial strata in white matter at both proximal and distant stimulation sites. Based on the electrophysiological properties and the white matter location for eliciting these responses, it is likely that the short-latency response is due to antidromic activation of corticogeniculate fibers, whereas the longer-latency response probably arises from orthodromic activation of geniculocortical fibers. These findings provide an electrophysiological demonstration that cortical afferent and efferent pathways are segregated within the white matter and that they can be selectively activated by focal stimulation. The fact that the fiber bundle model successfully predicted the trajectory of corticofugal fibers provides additional support for this model of white matter organization. A double labeling technique which combined orthograde axonal transport and neuronal degeneration was used to examine the topographic arrangement of corticofugal fibers in the white matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Regional white matter and neuropsychological functioning across the adult lifespan.

BACKGROUND: The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning. METHODS: One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups. RESULTS: The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory. CONCLUSIONS: The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter.

Adult↗
PubMed2006

Catecholaminergic activation of G-protein coupling in rat spinal cord: further evidence for the existence of dopamine and noradrenaline receptors in spinal grey and white matter.

[35S]GTPgammaS autoradiography of slide-mounted tissue sections was used to examine G-protein coupling in the rat spinal cord, as stimulated by dopamine, the D1 receptor agonist SKF 38393, noradrenaline, and noradrenaline in the presence of the alpha adrenoceptor antagonist, phentolamine. Measurements were obtained from the different laminae of spinal grey and from the dorsal, lateral, and ventral columns of white matter, at cervical, thoracic, and lumbar levels. At every level, there was a relatively strong basal incorporation of GTPgammaS in laminae II-III>lamina IV-X of spinal grey, even in presence of DPCPX to block endogenous activation by adenosine A1 receptors. Dopamine, and to a lesser degree SKF 38393, but not the D2 receptor agonist quinpirole, stimulated G-protein coupling in laminae IV-X. Both dopamine and SKF 38393 also induced a weak but significant activation throughout the white matter. In both grey and white matter, the activation by dopamine was markedly reduced in presence of a selective D1 receptor antagonist. Noradrenaline strongly stimulated coupling throughout the spinal grey at all levels, an effect that was uniformly reduced in the presence of phentolamine. With or without phentolamine, there was also significant stimulation by noradrenaline in the white matter. Under the same experimental conditions, alpha 1, alpha 2, and beta adrenergic receptor agonists failed to activate GTPgammaS incorporation in either grey or white matter. However, in the presence of selective alpha 1 or alpha 2 receptor antagonist, significant reductions of noradrenaline-stimulated GTPgammaS incorporation were observed in both grey and white matter. The beta antagonist propanolol reduced GTPgammaS incorporation in grey matter only. Thus, the results confirmed the existence of D1 dopamine receptors and of alpha 1, alpha 2, and beta adrenergic receptors in the grey matter of rat spinal cord. In white matter, they strongly suggested the presence of dopamine D1, and of alpha 1 and alpha 2 adrenergic receptors on glia and/or microvessels, that might be activated by diffuse transmission in vivo.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2005

A procedure for culturing astrocytes from white matter and the application of the siRNA technique for silencing the expression of their specific marker, S100A4.

White matter astrocytes have physiological functions which are distinct from those of astrocytes in gray matter. White matter becomes highly non-permissive to neurite growth after injury, but the role of white matter astrocytes in this process is incompletely understood. Current protocols for making primary astroglial cultures are inadequate for exploring the specific properties of white matter astrocytes in vitro. We describe a procedure for obtaining cultures of white matter astrocytes from the rodent corpus callosum. In this procedure, we take advantage of our previous finding that white, but not gray matter astrocytes express the calcium-binding protein S100A4. S100A4 expressing astrocytes are abundant in the corpus callosum, and we show that cultures, highly enriched in S100A4 expressing white matter astrocytes, can be reproducibly generated from this area. Key factors for successful cultures are (i) meticulous dissection of the corpus callosum from 4-day-old rats, and (ii) Percoll density gradient centrifugation to purify astrocytes. As a means of exploring the possible role of S100A4 in white matter astrocytes, we describe the use of the siRNA technique to eliminate the expression of S100A4 in our in vitro system.

Animals↗
PubMed2006

High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: a quantitative study.

GABA receptor activation in central nervous white matter may be protective during white matter hypoxia in the adult, and it may modify axonal conduction, especially in the developing brain. GABA uptake is important for the shaping of the GABA signal, but quantitative data are lacking for GABA uptake and GABA-metabolizing enzymes in central nervous white matter. We report that high-affinity uptake of GABA in adult pig corpus callosum, fimbria, subcortical pyramidal tracts, and occipital white matter is approximately 20% of that in temporal cortex gray matter. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures. This finding indicates that GAT-1 is an important GABA transporter in white matter and suggests that white matter GABA uptake is inhibited during tiagabine therapy. GABA transaminase activity in white structures was approximately 20% of neocortical values. Glutamate decarboxylase (GAD) activity in white structures was only 4% of that in neocortex (7-12 pmol/mg tissue x min(-1) versus approximately 200 pmol/mg tissue x min(-1)). Since white matter activity of citrate synthase of the tricarboxylic acid cycle was approximately 25% of neocortical values ( approximately 0.4 nmol/mg tissue x min(-1) versus approximately 1.5 nmol/mg tissue x min(-1)), the low GAD activity suggests a slower metabolic turnover of GABA in white than in gray matter.

4-Aminobutyrate Transaminase↗
PubMed2004

Magnetic resonance imaging of differential gray versus white matter injury following a mild or moderate hypoxic-ischemic insult in neonatal rats.

Selective white matter injury in the pre-mature infants suggests it has a greater susceptibility to hypoxia-ischemia. To investigate whether white matter injury would predominate following a mild hypoxic-ischemic insult, 7-day-old rats underwent either mild or moderate hypoxia-ischemia and magnetic resonance imaging 24 h later. Mild and moderate hypoxia-ischemia were produced by unilateral carotid artery occlusion plus exposure to hypoxia for either 45-50 or 90 min at ambient temperatures of 34.5 or 35.5 degrees C, respectively. Following mild hypoxia-ischemia, there was a significant increase in T(1) and T(2) within periventricular white matter (e.g. corpus callosum) in the hemisphere ipsilateral to the occlusion compared to that contralaterally and less of an increase within gray matter (e.g. cortex and striatum). This corresponded to relatively selective white matter injury detected histologically. Following a moderate hypoxia-ischemia, both gray and white matter was severely injured with marked increases in T(1) and T(2) occurring in both white and gray matter regions ipsilateral to the hypoxia-ischemia. We conclude that a mild insult, consisting of a short duration of hypoxia-ischemia at a slightly lower body temperature than a moderate hypoxic-ischemic insult, produces enhanced injury in white matter and a relative sparing of gray matter.

Animals↗
PubMed2004

Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity.

Gray matter changes have been demonstrated in several regions in schizophrenia. Particularly, the frontal and temporal cortices and amygdala-hippocampal region have been found decreased in volume and density in magnetic resonance imaging (MRI) studies. These abnormalities may reflect an aberrant neuronal network in schizophrenia, suggesting that white matter fibers connecting these regions may also be affected. However, it is unclear if particular white matter areas are (progressively) affected in schizophrenia and if these are related to the gray matter changes. Focal white matter changes in schizophrenia were studied in whole brain magnetic resonance images acquired from 159 patients with schizophrenia or schizophreniform disorder and 158 healthy comparison subjects using voxel-based morphometry. White matter density changes in the patients with schizophrenia were correlated to gray matter density changes and to illness severity. In the patients with schizophrenia, significant decreases in white matter density were found in the genu and truncus of the corpus callosum in the left and right hemisphere, in the right anterior internal capsule and in the right anterior commissure. No interactions between diagnosis and age were found. Increased illness severity was correlated with low density of the corpus callosum and anterior commissure. Decreased corpus callosum density correlated with decreased density of thalamus, lateral inferior frontal and insular gray matter in patients and controls and with decreased density of medial orbitofrontal and superior temporal gyri in patients. Decreased internal capsule and anterior commissure density correlated with increased caudate, and globus pallidus density in patients and controls. These findings suggest aberrant inter-hemispheric connectivity of anterior cortical and sub-cortical brain regions in schizophrenia, reflecting decreased hemispheric specialisation in schizophrenia.

Adult↗
PubMed2005

Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter.

The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. When cholera toxin-b was injected into the rostral periaqueductal gray matter, many double-labeled cells were observed in the median preoptic nucleus in warm-exposed rats, but few were seen in cold-exposed rats. On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenesis, respectively.

Animals↗
PubMed2004

State-related changes in cerebral white matter may underlie psychosis exacerbation.

Previous reports have described accelerated loss of cerebral white matter in schizophrenia. Others have reported changes of ventricle volumes in schizophrenic patients, with greatest increases following remission of psychotic symptoms. In this study changes in cerebral white matter volumes and psychotic symptoms were measured in 16 recently decompensated schizophrenic patients from neuroleptic-free baseline to 4 weeks later during treatment with antipsychotics. Serial white matter assessments were also performed in eight controls at similar intervals. Thirteen of 16 patients showed reduction of psychotic symptoms (reduction of SAPS scores by 24.4+/-12.6) during treatment. Three patients failed to respond (increase of SAPS scores by 15.7+/-13.8). Serial volumetric studies of cerebral white matter during the 4-week period showed a decrease of white matter volume in the responders by 8.2+/-8.2 cm(3) (P=0.003). Patients who failed to respond showed a non-significant increase in white matter during the same period by 11.4+/-11.7 cm(3). Absolute and percentage changes change in white matter volumes during the 4-week period were positively correlated with changes in SAPS scores (both P<0.01). Cerebral white matter, composed of myelin-containing oligodendrocytes, is highly sensitive to excitotoxicity. Swelling of myelin and of white matter, associated interference with the speed of neurotransmission through myelinated axons, and dyssynchrony of information processing by subcortical and cortical networks may be associated with psychosis exacerbation. Partial remission of symptoms may mark temporary reduction of an active, toxic process that interferes with information processing.

Adult↗