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PubMed2001

Differentiation of glucose transport in human brain gray and white matter.

Localized 1H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible Michaelis-Menten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, V(max), to the cerebral metabolic utilization rate of glucose, CMR(Glc), was 3.2 +/- 0.10 and 3.9 +/- 0.15 for gray matter and white matter using the standard transport model and 1.8 +/- 0.10 and 2.2 +/- 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant K(m) was 6.2 +/- 0.85 and 7.3 +/- 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 +/- 0.66 and 1.7 +/- 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMR(Glc) in white matter, this finding suggests that blood--brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood--brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.

Adult↗

PubMed2001

Adenosine in relation to calcium homeostasis: comparison between gray and white matter ischemia.

In vitro studies suggest that adenosine may attenuate anoxic white matter damage as an intrinsic protective substance. The authors investigated ischemic alterations of purines in relation to tissue depolarization and extracellular calcium and amino acid concentrations in vivo using microdialysis and ion-selective electrodes in cortical gray and subcortical white matter of 10 cats during 120 minutes of global brain ischemia. Immediately on induction of ischemia, regional cerebral blood flow ceased in all cats in both gray and white matter. The direct current potential rapidly decreased, the decline being slower and shallower in white matter. Extracellular calcium levels decreased in gray matter. In contrast, they first increased in white matter and started to decrease below control levels only after approximately 30 minutes. Adenosine levels transiently increased in both tissue compartments; the peak was delayed by 30 minutes in white matter. Thereafter, levels declined faster in gray than in white matter and remained elevated in the latter tissue compartment. Inosine and hypoxanthine elevations were progressive in both regions but smaller in white matter. Levels of gamma-aminobutyric acid, another putatively protective agent, steadily increased, starting immediately in gray matter and delayed by almost 1 hour in white matter. The delayed and prolonged accumulation of adenosine correlates with a slower adenosine triphosphate breakdown in white matter ischemia and may result in protection of white matter by suspending cellular calcium influx.

Adenosine↗

PubMed1984

Positional distribution of acyl and alk-1-enyl groups in grey and white matter ethanolamine and choline phosphoglycerides of a marsupial, the koala (Phascolarctos cinereus).

The major phosphoglycerides in grey and white matter from the brain of the koala have been separated and examined. The major polyunsaturated fatty acids present in both the diacyl- and alk-1-enyl acylglycerophosphorylethanolamines from grey matter were 22:6 omega 3, 20:4 omega 6, and 22:4 omega 6. In both grey and white matter, 22:6 omega 3 and 20:4 omega 6 were concentrated in the 2-position of diacylglycerophosphorylethanolamines and 22:4 omega 6 in the 2-position of alk-1-enylacylglycerophosphorylethanolamines; polyunsaturated fatty acid levels were higher in diacylglycerophosphorylethanolamines. Ethanolamine phosphoglyceride fractions from grey matter were enriched in polyunsaturated fatty acids compared with those from white matter. The acyl groups 18:0, 18:1, and 16:0 and their alk-1-enyl analogues were prominent in grey and white matter ethanolamine phosphoglycerides; 18:1 was dominant in white matter alk-1-enylacylglycerophosphorylethanolamines. The plasmalogen composition of ethanolamine phosphoglycerides was 55% in grey matter and 76% in white matter. Choline phosphoglycerides contained negligible plasmalogen and low polyunsaturated fatty acid levels. Diacylglycerophosphorylcholine was characterized by high levels of 16:0 and 18:1. Similar acyl group distributions were estimated in the 1-position in both grey and white matter, 16:0 being present at greater than 50%. The presence of the molecular species 18:0/22:6 omega 3 was indicated in grey matter diacylglycerophosphorylethanolamine, 18:1/18:1 in white matter alk-1-enylcylglycerophosphorylethanolamine, and 16:0/18:1 in white matter diacylglycerophosphorylcholine.

Acylation↗

PubMed2001

Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Gray matter may be affected by multiple sclerosis (MS), a white matter disease. Magnetization transfer ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS. In this study, we evaluated the amount of MTR of gray matter among patients with relapsing-remitting MS and healthy control subjects as well as the correlation between gray matter MTR abnormality and neurologic disability associated with relapsing-remitting MS. METHODS: We obtained fast spin-echo dual-echo and magnetization transfer (with and without MT saturation pulses) images from eighteen patients with relapsing-remitting MS and 18 age-matched healthy control subjects. Gray matter was segmented using a semiautomated system. Gray matter MTR histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and gray matter volumes were obtained for statistical analysis. RESULTS: A significant difference was found in gray matter MTR between patients with relapsing-remitting MS and healthy subjects (mean and median). Gray matter MTR histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P =.01). There was also an inverse correlation between mean MTR of gray matter and total T2 lesion volume. CONCLUSION: The MTR of gray matter significantly differed between patients with relapsing-remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole brain, and neuronal damage accumulates in step with T2 lesion volume. Our finding of the relationship between gray matter MTR and EDSS indicates that measurement of gray matter abnormality may be a potentially useful tool for assessing clinical disability in MS.

Adult↗

PubMed2002

Brain size and grey matter volume in the healthy human brain.

Magnetic resonance imaging was used to evaluate the influence of sex and brain size on compartmental brain volumes (grey matter, white matter, CSF) in a large and well-matched sample of neurologically normal women (n = 50) and men (n = 50). As expected, we found a significant sex difference for the absolute volumes of total brain, grey matter, white matter and CSF, with greater volumes for men. Relating these compartmental volume measures to brain volume resulting in proportional volume measures revealed a higher proportion of grey matter in women. No significant sex differences were found for white matter and CSF proportions. However, when the influence of sex was partialized out by regression analyses, brain volume explained 40-81% of the variance of the absolute grey matter, white matter and CSF volumes. Performing these regression analyses for the proportional volume measures revealed that brain volume explained approximately 16% of the variance in grey matter proportion. Sex or the interaction between sex and brain volume revealed no additional predicitve values. Interestingly, the correlation between brain volume and grey matter proportion was negative, with larger brains exhibiting relatively smaller proportions of grey matter. Thus, sex is not the main variable explaining the variability in grey matter volume. Rather, we suggest that brain size is the main variable determining the proportion of grey matter.

Adult↗

PubMed1999

Differential effects of spinal cord gray and white matter on process outgrowth from grafted human NTERA2 neurons (NT2N, hNT).

To investigate host effects on grafts of pure, postmitotic, human neurons, we assessed the morphologic and molecular phenotype of purified NTera2N (NT2N, hNT) neurons implanted into the spinal cord of athymic nude mice. NT2N neurons were implanted into both spinal cord gray matter and white matter of neonatal, adolescent, and adult mice and were evaluated at postimplantation times up to 15 months. NT2N neurons remained at the implantation site and showed process integration into all host areas, and each graft exhibited similar phenotypic features regardless of location or host age at implantation. Evidence of host oligodendrocyte ensheathment of NT2N neuronal processes was seen, and grafted NT2N neurons acquired and maintained the morphologic and molecular phenotype of mature neurons. The microenvironments of host gray matter and white matter appear to exert differential effects on implanted neuronal processes, because consistent differences were noted in the morphologies of graft processes extending into white matter versus gray matter. NT2N processes extended for long distances (>2 cm) within white matter, whereas NT2N processes located within gray matter had shorter trajectories. This suggests that NT2N neurons integrate similarly into spinal cord gray matter and white matter, but they extend processes that respond differentially to gray matter and white matter cues. Further studies of the model system described here may identify the host molecular signals that support and direct integration of grafted human neurons as well as the outgrowth of their processes in the nervous system.

Aging↗

PubMed2006

White matter fractional anisotropy and outcome in schizophrenia.

OBJECTIVE: Disparate white matter fractional anisotropy (FA) findings have been reported in patients with schizophrenia in recent years. This may in part reflect heterogeneity of subjects in the studies, including differences in outcome and severity of the illness. We examined whether there is a relationship between white matter FA and outcome in patients with schizophrenia. METHOD: Diffusion-tensor images were obtained in 41 normal subjects and 104 patients with schizophrenia, divided into good-outcome (n=51) and poor-outcome (Kraepelinian; n=53) subtypes based on their ability for self-care. White matter FA and its relationship to regional tissue volumes were evaluated across 40 individual Brodmann's areas using a semi-automated parcellation technique. RESULTS: Overall white matter FA was lower in schizophrenia patients than normal subjects, with regional reductions in widespread temporoparietal and selected prefrontal white matter regions. In schizophrenia patients, lower regional white matter FA was associated with lower regional gray matter volumes. In comparison to normal subjects, overall white matter FA was reduced in patients with poor outcomes in both hemispheres, but to a lesser extent and only in the right hemisphere in good-outcome patients. Lower regional FA was associated with larger regional white matter volumes in good-outcome group. CONCLUSIONS: Global FA reductions implicate white matter as tissue type in the pathophysiology of schizophrenia. In contrast to poor outcome, good outcome in schizophrenia patients may be associated with less extensive FA reductions, higher FA in regional frontal and cingulate white matter, and correlated increases in regional white matter volumes, particularly in the left hemisphere.

Adult↗

PubMed2006

Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD.

BACKGROUND: Silent cerebral white matter lesions are observed on magnetic resonance imaging (MRI) scans in elderly people, and they are related to vascular risk factors, particularly hypertension. No data on the prevalence and risk factors of white matter lesions in patients with chronic kidney disease (CKD) are available. The aim is to analyze the prevalence of white matter lesions and their determinants in this population. METHODS: We studied 52 patients without diabetes with CKD (stage 3 or 4) aged 30 to 60 years (average, 49 years) and a group of 32 normotensive control subjects. MRI studies were performed and subcortical and periventricular white matter lesions were evaluated by using semiquantitative measures. Patients were classified into 2 groups depending on the presence or absence of white matter lesions. Echocardiographic studies and measures of markers of systemic inflammation (C-reactive protein and interleukin 6) also were performed. RESULTS: White matter lesions were more prevalent in patients with CKD than controls (33% versus 6%; P = 0.008). Patients with CKD who had white matter lesions were older; had a greater history of cardiovascular disease and vascular nephropathy as a primary cause of renal disease and greater levels of systolic blood pressure, pulse pressure, left ventricular mass index, and C-reactive protein; and were administered more antihypertensive drugs than patients with CKD without white matter lesions. Stage and duration of CKD were not related to the presence of white matter lesions. After adjusting for several factors, only vascular nephropathy (odds ratio, 15.6; 95% confidence interval, 1.27 to 191.54; P = 0.03) independently predicted an increased risk for white matter lesions. CONCLUSION: One third of middle-aged patients with CKD have silent cerebral white matter lesions. Vascular nephropathy seems to be the most important factor related to the presence of these lesions, suggesting that white matter lesions reflect ischemic brain damage caused by generalized vascular damage.

Adult↗

PubMed1997

Quantitative MRI of the gray-white matter distribution in traumatic brain injury.

Quantitative analyses were performed on magnetic resonance images (MRIs) obtained from the brains of 31 traumatic brain-injured (TBI) patients and 25 normal control subjects. The quantitative analyses involved comparisons of the shapes of proton density gray scale pixel histograms obtained from both 3-mm and 5-mm slice thickness. Image segmentation was accomplished by a multispectral fuzzy C-means and/or k-nearest-neighbor (kNN) algorithms and manual classification was used to label segmented classes into CSF, white matter, and other. Shape descriptors were derived from the pixel intensity histograms of the combined gray matter and white matter classes for each MRI slice. Statistical analyses revealed significant differences in pixel intensity distributions between TBI and control subjects. Normal control subjects tended to exhibit bimodal gray matter-white matter histograms, whereas, TBI patients tended to exhibit unimodal gray matter-white matter histograms. In the control subjects the pixels intermediate in intensity between gray and white matter were located primarily at the border between the gray and white matter, whereas TBI patients exhibited a thickening of the number of intermediate pixels at the border as well as an increase in intermediate pixels in the middle of the gray and white matter. The greater the severity of TBI, then the larger the number of intermediate intensity pixels within and between gray and white matter. Further analyses demonstrated shifts in magnetic resonance relaxation times in gray and white matter in TBI patients, which suggested that the tendency toward unimodality in TBI patients represents a pathological reduction in brain differentiation due to measurable biophysical change.

Adult↗

PubMed2004

Clinical significance of cerebral white matter lesions in older Asians with suspected dementia.

BACKGROUND: cerebral white matter lesions are commonly seen on neuroimaging in older people and have been associated with clinical features such as gait abnormalities, urinary incontinence and depression. The significance of cerebral white matter lesions in older people with dementia remains uncertain. OBJECTIVES: to study the association between cerebral white matter lesions and the presence or absence of dementia in a group of elderly Asian patients; and to determine the clinical significance of cerebral white matter lesions in patients who are diagnosed to have dementia in terms of associated clinical features and the impact of cerebral white matter lesions on cognitive status. METHODS: for the first objective, the records of 141 older people of Asian ethnicity presenting to a memory clinic for the evaluation of suspected dementia were reviewed to compare the prevalence of cerebral white matter lesions in patients who did not fulfil the criteria for dementia, patients diagnosed to have Alzheimer's disease and patients diagnosed to have vascular dementia. For the second objective, 115 of these patients who were diagnosed to have dementia were studied to determine if demented patients with cerebral white matter lesions were more likely to have urinary incontinence, Parkinsonism, depression and greater severity of dementia. In addition, a comparison was made between demented patients with cerebral white matter lesions and those without cerebral white matter lesions in terms of psychometric assessment scores. RESULTS: cerebral white matter lesions were more common in Asian patients with vascular dementia. Demented patients with cerebral white matter lesions were also found to have more severe dementia and greater functional disability. CONCLUSION: cerebral white matter lesions are common, and are associated with greater functional disability in elderly Asian patients with dementia.

Aged↗

PubMed2003

Quantitative analysis of gray- and white-matter volumes and glucose metabolism in Sturge-Weber syndrome.

The progressive nature of Sturge-Weber syndrome is well known, but the mechanisms of focal cortical and subcortical degeneration in this disorder are poorly understood. In the present study, we assessed the structural and functional integrity of gray and white matter in unihemispheric Sturge-Weber syndrome using quantitative magnetic resonance imaging (MRI) volumetry and MRI-based partial volume correction of [18F]fluorodeoxyglucose positron emission tomographic (PET) images. Gray- and white-matter volumes and glucose metabolism were measured in three brain regions (parieto-occipital underneath the angioma, temporal, and frontal) in six children with Sturge-Weber syndrome (two infants, ages 6 and 9 months; four older children, ages 4 to 14 years), all with unilateral parieto-occipital leptomeningeal angiomatosis. The gray-matter volumes ipsilateral to the angioma were smaller in all children, with the posterior regions underneath the angioma the most affected. In the infants, the white-matter volumes were increased in the region of the angioma, whereas in the regions remote from the angioma in the infants and in all regions of the older children, there were large decreases in white-matter volume. The decreases of frontal and temporal white-matter volume were more pronounced than the corresponding gray-matter volume decreases. The PET studies showed severe hypometabolism in the parieto-occipitalregion underneath the angioma in all of the children. However, the two infants showed glucose hypermetabolism in the frontal and temporal cortical gray matter, whereas these regions had relatively preserved metabolism in the older patients. These results demonstrate differential involvement of gray and white matter in Sturge-Weber syndrome. Both structural and functional abnormalities extend well beyond the angioma, indicating widespread abnormalities of growth and development of the affected hemisphere. Furthermore, whereas increased white-matter volume underlying the angioma may be seen in infants, ipsilateral white-matter regions outside the angioma show volume loss both in infants and in older patients. Extensive gray- and white-matter volume loss and hypometabolism ipsilateral to the angioma likely contribute to the frequently observed progressive cognitive dysfunction in these patients, regardless of the extent of the angioma.

Adolescent↗

PubMed2004

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Adult↗

PubMed2006

What is soil organic matter worth?

The conservation and restoration of soil organic matter are often advocated because of the generally beneficial effects on soil attributes for plant growth and crop production. More recently, organic matter has become important as a terrestrial sink and store for C and N. We have attempted to derive a monetary value of soil organic matter for crop production and storage functions in three contrasting New Zealand soil orders (Gley, Melanic, and Granular Soils). Soil chemical and physical characteristics of real-life examples of three pairs of matched soils with low organic matter contents (after long-term continuous cropping for vegetables or maize) or high organic matter content (continuous pasture) were used as input data for a pasture (grass-clover) production model. The differences in pasture dry matter yields (non-irrigated) were calculated for three climate scenarios (wet, dry, and average years) and the yields converted to an equivalent weight and financial value of milk solids. We also estimated the hypothetical value of the C and N sequestered during the recovery phase of the low organic matter content soils assuming trading with C and N credits. For all three soil orders, and for the three climate scenarios, pasture dry matter yields were decreased in the soils with lower organic matter contents. The extra organic matter in the high C soils was estimated to be worth NZ$27 to NZ$150 ha(-1) yr(-1) in terms of increased milk solids production. The decreased yields from the previously cropped soils were predicted to persist for 36 to 125 yr, but with declining effect as organic matter gradually recovered, giving an accumulated loss in pastoral production worth around NZ$518 to NZ$1239 ha(-1). This was 42 to 73 times lower than the hypothetical value of the organic matter as a sequestering agent for C and N, which varied between NZ$22,963 to NZ$90,849 depending on the soil, region, discount rates, and values used for carbon and nitrogen credits.

Agriculture↗

PubMedDate not supplied

White matter lesions in panencephalopathic type of Creutzfeldt-Jakob disease: MR imaging and pathologic correlations.

BACKGROUND AND PURPOSE: A panencephalopathic type of Creutzfeldt-Jakob disease (pCJD) is characterized by the extensive involvement of the cerebral white matter as well as the cerebral gray matter. It has been a point of controversy, however, whether the white matter changes represent primary or secondary degeneration. The aim of this study was to elucidate, by using MR images and histologic examinations, whether the white matter lesions in pCJD are primary or secondary degeneration. METHODS: Serial changes of T2 hyperintensities and histologic findings of six autopsy-proved cases of pCJD were retrospectively analyzed. RESULTS: Serial MR images of brains affected by pCJD revealed that T2 hyperintensities appeared in the cerebral gray matter 2-5 months after onset and in the cerebral white matter around the lateral ventricles approximately 5 months after onset. They rapidly extended to deep and subcortical white matter during the next several months and then to the entire cerebral white matter 10 months after onset. Histologic examination of the white matter lesions revealed spongy changes or tissue rarefaction associated with gemistocytic astrocytosis, which indicates primary involvement of the white matter. At the terminal stages of cases with a longer clinical course, MR images showed T2 hyperintensities in the corticospinal tracts in the internal capsule and brain stem, which histologically disclosed loss of myelin and axons accompanied by fibrillary gliosis that indicates secondary degeneration. CONCLUSION: Cerebral white matter lesions in pCJD were considered to be primary changes of the disease, but the lesions of the corticospinal tracts were secondary to cortical or cerebral or both white matter lesions.

Aged↗

PubMed1999

Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging.

BACKGROUND: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. RESULTS: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.

Adult↗

PubMed2000

Cerebral white matter lesions and depressive symptoms in elderly adults.

BACKGROUND: There is evidence for a vascular cause of late-life depression. Cerebral white matter lesions are thought to represent vascular abnormalities. White matter lesions have been related to affective disorders and a history of late-onset depression in psychiatric patients. Their relation with mood disturbances in the general population is not known. We investigated the relation between white matter lesions and the presence of depressive symptoms or a history of depression in a population-based study. METHODS: In a sample of 1077 nondemented elderly adults, we assessed the presence and severity of subcortical and periventricular white matter lesions using magnetic resonance imaging, presence of depressive symptoms, and history of depression. Using multiple regression analysis, we examined the relation among white matter lesions, depressive symptoms, and history of depression. RESULTS: Most of the subjects had white matter lesions. Persons with severe white matter lesions (upper quintile) were 3 to 5 times more likely to have depressive symptoms as compared with persons with only mild or no white matter lesions (lowest quintile) (periventricular odds ratio [OR] = 3.3; 95% confidence interval [CI], 1.2-9.5; subcortical OR = 5.4; 95% CI, 1.8-16.5). In addition, persons with severe subcortical but not periventricular white matter lesions were more likely to have had a history of depression with an onset after age 60 years (OR = 3.4; 95% CI, 1.1-10.7) compared with persons with only mild or no white matter lesions. CONCLUSION: The severity of subcortical white matter lesions is related to the presence of depressive symptoms and to a history of late-onset depression.

Age of Onset↗

PubMed1994

Inhibitory and excitatory projections from the dorsal raphe nucleus to neurons in the dorsolateral periaqueductal gray matter in slices of midbrain maintained in vitro.

Coronal slices of midbrain from adult rats, maintained in an interface chamber at 33-35 degrees C, were used to investigate projections from the dorsal raphe nucleus to the dorsolateral periaqueductal gray matter. Extracellular recordings were made from neurons in the dorsolateral periaqueductal gray matter. The majority of cells were silent but activity could readily be induced by iontophoretic application of D, L-homocysteic acid from the recording pipette. Neuronal perikarya in the dorsal raphe nucleus were activated either by topical application of 15-100 nl droplets of 1 or 10 mM D,L-homocysteic acid or by iontophoresis into the dorsal raphe nucleus of 0.1 M D,L-homocysteic acid from a five-barrelled glass micropipette. Both forms of stimulation evoked increases or decreases in firing in neurons in the dorsolateral periaqueductal gray matter. The excitatory responses were evoked only from stimulation sites in the dorsal subnucleus of the dorsal raphe nucleus, whilst inhibitory responses could be evoked by stimulating throughout the nucleus. 5-Hydroxytryptamine was applied by iontophoresis to 55 neurons in the dorsolateral periaqueductal gray matter. Of these, 89% were inhibited whilst the remaining 11% were excited. No unresponsive cells were found. In a second series of experiments anterograde transport of biocytin was used to study projections from the dorsal raphe nucleus to the periaqueductal gray matter in vitro. Following injections of pellets of biocytin into the dorsal subnucleus of the dorsal raphe nucleus, two types of labelled axons could be distinguished which had either smooth or beaded profiles. Both types of axon could be followed into the region of the dorsolateral periaqueductal gray matter, from which recordings were made in the electrophysiological experiments. In contrast, following deposits of biocytin into the ventral half of the periaqueductal gray matter, very few labelled axons were found in the dorsolateral periaqueductal gray matter, although the ventrolateral periaqueductal gray matter was heavily labelled. We conclude that both excitatory and inhibitory projections from the dorsal raphe nucleus to the dorsolateral periaqueductal gray matter are present in the coronal midbrain slice preparation. Excitatory projections originate from the dorsal subnucleus of the dorsal raphe nucleus and may be mediated by a direct pathway. The inhibitory effects evoked from the ventral half of the dorsal raphe nucleus are probably mediated indirectly, perhaps by activation of inhibitory interneurons in the ventrolateral periaqueductal gray matter.

Animals↗

PubMed2005

Focal brain matter differences associated with lifetime alcohol intake and visual attention in male but not in female non-alcohol-dependent drinkers.

The purpose of this study was to investigate whether current or lifetime alcohol intake is related to focal gray and white matter in healthy non-alcohol-dependent drinkers, and, if so, whether these densities are related to functional brain activity associated with visual attention. Voxel-based morphometric analyses of gray- and white-matter densities, and event-related potentials in response to a visual-attention task were determined in 47 male drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg). All participants had a negative personal and family history of alcohol dependence to reduce possible confounding by genetic factors related to alcohol dependence. In males, mean lifetime alcohol intake was negatively associated with gray-matter density and positively associated with white-matter density in the right frontal gyrus (BA 6) and the right parietal region (BA 40). Right frontal (but not right parietal) gray and white matter in males correlated with the P3 amplitude of the event-related potentials elicited in a visual-attention task. In females, mean lifetime alcohol intake was not associated with gray- or white-matter density. Current alcohol intake was unrelated to gray or white matter in both males and females. In conclusion, lifetime alcohol intake is associated with focal gray-matter decreases and white-matter increases in the right frontal and right parietal brain regions in non-alcohol-dependent males, but not in females. These alcohol-related differences in focal brain matter in males are associated with differences in brain function related to visual attention. As the confounding effects of genetic factors were reduced, the present results may selectively relate to the effects of alcohol intake on focal brain matter.

Alcohol Drinking↗