ABSTRACT
Monitoring sustainable urban development requires comparable geospatial information on cities across several thematic domains. Here we present the first global database combining such information with city extents. The Global Human Settlement Urban Centre Database (GHS-UCDB) is produced by geospatial data integration to characterise more than 10,000 urban centres worldwide. The database is multi-dimensional and multi-temporal, containing 28 variables across five domains and having multitemporal attributes for one or more epochs when the UC are delineated (1975-1990-2000-2015). Delineation of urban centres for the year 2015 is performed via a logic of grid cell population density, population size, and grid cell contiguity defined by the Degree of Urbanisation method. Each of the urban centres has 160 attributes, including a validation assessment. The novel aspects of this database concern the thematic richness and temporal depth of the variables (across geography, socio-economic, environmental, disaster risk reduction, and sustainable development domains) and the type of geo-information provided (location and extent), featuring an overall consistency that allows comparative analyses across locations and time.
ABSTRACT
The application of last-generation spatial data modelling, integrating Earth Observation, population, economic and other spatially explicit data, enables insights into the sustainability of the global urbanisation processes with unprecedented detail, consistency, and international comparability. In this study, the land use efficiency indicator, as developed in the Sustainable Development Goals, is assessed globally for the first time at the level of Functional Urban Areas (FUAs). Each FUA includes the city and its commuting zone as inferred from statistical modelling of available spatial data. FUAs represent the economic area of influence of each urban centre. Hence, the analysis of land consumption within their boundary has significance in the fields of spatial planning and policy analyses as well as many other research areas. We utilize the boundaries of more than 9,000 FUAs to estimate the land use efficiency between 1990 and 2015, by using population and built-up area data extracted from the Global Human Settlement Layer. This analysis shows how, in the observed period, FUAs in low-income countries of the Global South evolved with rates of population growth surpassing the ones of land consumption. However, in almost all regions of the globe, more than half of the FUAs improved their land use efficiency in recent years (2000-2015) with respect to the previous decade (1990-2000). Our study concludes that the spatial expansion of urban areas within FUA boundaries is reducing compactness of settlements, and that settlements located within FUAs do not display higher land use efficiency than those outside FUAs.
ABSTRACT
Several global high-resolution built-up surface products have emerged over the last five years, taking full advantage of open sources of satellite data such as Landsat and Sentinel. However, these data sets require validation that is independent of the producers of these products. To fill this gap, we designed a validation sample set of 50 K locations using a stratified sampling approach independent of any existing global built-up surface products. We launched a crowdsourcing campaign using Geo-Wiki ( https://www.geo-wiki.org/ ) to visually interpret this sample set for built-up surfaces using very high-resolution satellite images as a source of reference data for labelling the samples, with a minimum of five validations per sample location. Data were collected for 10 m sub-pixels in an 80 × 80 m grid to allow for geo-registration errors as well as the application of different validation modes including exact pixel matching to majority or percentage agreement. The data set presented in this paper is suitable for the validation and inter-comparison of multiple products of built-up areas.
ABSTRACT
The dynamics of societal material stocks such as buildings and infrastructures and their spatial patterns drive surging resource use and emissions. Two main types of data are currently used to map stocks, night-time lights (NTL) from Earth-observing (EO) satellites and cadastral information. We present an alternative approach for broad-scale material stock mapping based on freely available high-resolution EO imagery and OpenStreetMap data. Maps of built-up surface area, building height, and building types were derived from optical Sentinel-2 and radar Sentinel-1 satellite data to map patterns of material stocks for Austria and Germany. Using material intensity factors, we calculated the mass of different types of buildings and infrastructures, distinguishing eight types of materials, at 10 m spatial resolution. The total mass of buildings and infrastructures in 2018 amounted to â¼5 Gt in Austria and â¼38 Gt in Germany (AT: â¼540 t/cap, DE: â¼450 t/cap). Cross-checks with independent data sources at various scales suggested that the method may yield more complete results than other data sources but could not rule out possible overestimations. The method yields thematic differentiations not possible with NTL, avoids the use of costly cadastral data, and is suitable for mapping larger areas and tracing trends over time.
Subject(s)
Austria , GermanyABSTRACT
Neuropathological studies, using a variety of techniques, have reported a decrease in Purkinje cell (PC) density in the cerebellum in autism. We have used a systematic sampling technique that significantly reduces experimenter bias and variance to estimate PC densities in the postmortem brains of eight clinically well-documented individuals with autism, and eight age- and gender-matched controls. Four cerebellar regions were analyzed: a sensorimotor area comprised of hemispheric lobules IV-VI, crus I & II of the posterior lobe, and lobule X of the flocculonodular lobe. Overall PC density was thus estimated using data from all three cerebellar lobes and was found to be lower in the cases with autism as compared to controls, an effect that was most prominent in crus I and II (p<0.05). Lobule X demonstrated a trend towards lower PC density in only the males with autism (pâ=â0.05). Brain weight, a correlate of tissue volume, was found to significantly contribute to the lower lobule X PC density observed in males with autism, but not to the finding of lower PC density in crus I & II. Therefore, lower crus I & II PC density in autism is more likely due to a lower number of PCs. The PC density in lobule X was found to correlate with the ADI-R measure of the patient's use of social eye contact (R²â=â-0.75, pâ=â0.012). These findings support the hypothesis that abnormal PC density may contribute to selected clinical features of the autism phenotype.
Subject(s)
Autistic Disorder/pathology , Purkinje Cells/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.
Subject(s)
Autistic Disorder/pathology , Cerebellum/pathology , Animals , Autistic Disorder/genetics , Autistic Disorder/immunology , Autistic Disorder/metabolism , Autistic Disorder/therapy , Cell Adhesion Molecules, Neuronal/metabolism , Cerebellar Diseases/genetics , Cerebellar Diseases/immunology , Cerebellum/immunology , Cerebellum/metabolism , Cerebellum/physiopathology , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Disease Models, Animal , Extracellular Matrix Proteins/metabolism , Gene-Environment Interaction , Glutamic Acid/metabolism , Humans , Magnetic Resonance Imaging , Mitochondria/metabolism , Movement Disorders/etiology , Movement Disorders/physiopathology , Nerve Tissue Proteins/metabolism , Neurotransmitter Agents/metabolism , Oxidative Stress , Reelin Protein , Serine Endopeptidases/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
Like humans, rhesus monkeys show cognitive decline and this review considers what structural age-related changes underlie this decline. Some structural measures do not alter significantly with age. These include brain weight, overall cortical thickness; numbers of cortical neurons; and numbers of astrocytes and microglial cells. Other structural measures change with age, but the change does not correlate with cognitive decline. These changes include nerve fiber loss from some fiber tracts, degeneration, and regeneration of myelin sheaths, and increase in the frequency of oligodendrocytes. Among the structural measures that increase in frequency with age and also correlate with cognitive decline are the increased frequency of degenerating myelin sheaths and a loss of nerve fibers from some fiber tracts; and the loss of synapses and dendritic spines from upper layers of prefrontal cortex. Consequently, the existing data suggest that cognitive decline correlates with changes in myelinated nerve fibers and with disconnections between and within cortical areas, as reflected by the age-related loss of synapses and of dendritic spines from some cortical areas.
Subject(s)
Aging/pathology , Cerebrum/pathology , Cognition Disorders/pathology , Macaca mulatta , Monkey Diseases/pathology , Animals , Female , Male , Myelin Sheath/ultrastructure , Nerve Degeneration/pathology , Neuroglia/ultrastructure , Neurons/ultrastructureABSTRACT
Prenatal protein malnutrition alters the structure and function of the adult rat hippocampal formation. The current study examines the effect of prenatal protein malnutrition on numbers of parvalbumin-immunoreactive (PV-IR) GABAergic interneurons, which are important for perisomatic inhibition of hippocampal pyramidal neurons. Brain sections from prenatally protein malnourished and normally nourished rats were stained for parvalbumin and PV-IR neurons were quantified using stereology in the dentate gyrus, CA3/2 and CA1 subfields, and the subiculum for both cerebral hemispheres. Results demonstrated that prenatal malnutrition did not affect the number of PV-IR interneurons in the hippocampus. Since prenatal protein malnutrition reduces total neuron numbers in the CA1 subfield (1), this results in an altered ratio of PV-IR interneurons to total neuronal numbers (from 1:22.9 in controls to 1:20.5 in malnourished rats). Additionally, there was no hemispheric asymmetry of either PV-IR neuron numbers or ratio of PV-IR:total neuron numbers.
Subject(s)
Dentate Gyrus/cytology , Interneurons/metabolism , Parvalbumins/metabolism , Prenatal Exposure Delayed Effects/metabolism , Protein-Energy Malnutrition/metabolism , Animals , Dentate Gyrus/drug effects , Dentate Gyrus/pathology , Female , Male , Neurons/cytology , Neurons/pathology , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social-emotional behaviors as well as functioning of interrelated areas.
Subject(s)
Autistic Disorder/pathology , Gyrus Cinguli/pathology , Interneurons/pathology , Neurons/pathology , Temporal Lobe/pathology , Adolescent , Adult , Cell Count , Cell Size , Female , Humans , Male , Middle Aged , Reference Values , Young AdultABSTRACT
BACKGROUND: Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aß levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (nâ=â724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals. CONCLUSIONS/SIGNIFICANCE: Cortical Aß and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia.
Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Neocortex/metabolism , Neocortex/pathology , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Female , Hippocampus/diagnostic imaging , Hippocampus/metabolism , Hippocampus/pathology , Humans , Magnetic Resonance Imaging , Male , Neocortex/diagnostic imaging , Radiography , tau Proteins/cerebrospinal fluid , tau Proteins/metabolismABSTRACT
Autism is a behaviorally defined disorder with deficits in social interaction, communication, atypical behaviors, and restricted areas of interest. Postmortem studies of the brain in autism have shown a broad spectrum of abnormalities in the cerebellum and neocortex, involving limbic regions such as anterior cingulate cortex (ACC, Brodmann's area 24). Using stereological techniques, we analyzed quantitatively cytoarchitectonic subdomains of the ACC (areas 24a, b, c) with regard to cell packing density and cell size. Microscopic examination of the ACC was also done to identify any neuropathologies. Results showed a significant decrease in cell size in layers I-III and layers V-VI of area 24b and in cell packing density in layers V-VI of area 24c. Direct comparisons revealed irregular lamination in three of nine autism brains and increased density of neurons in the subcortical white matter in the remaining cases. Because previous studies have suggested that von Economo neurons (VENs) may be altered in autism, a preliminary study of their density and size was undertaken. VEN density did not differ between autism and control brains overall. However, among the nine autism cases, there were two subsets; three brains with significantly increased VEN density and the remaining six cases with reduced VEN density compared to controls. Collectively, the findings of this pilot study may reflect the known heterogeneity in individuals with autism and variations in clinical symptomotology. Further neuroanatomic analyses of the ACC, from carefully documented subjects with autism, could substantially expand our understanding of ACC functions and its role in autism.
Subject(s)
Autistic Disorder/classification , Autistic Disorder/pathology , Brain Mapping , Cerebral Cortex/pathology , Gyrus Cinguli/pathology , Adolescent , Adult , Cell Count , Functional Laterality , Humans , Male , Middle Aged , Neuroanatomy , Neurons/pathology , Stereotaxic Techniques , Young AdultABSTRACT
Alterations in the cerebellum have been described as a neuropathological feature of autism. Although numerous studies have focused on the Purkinje cell (PC), the projection neuron of the cerebellar cortex, PC function is critically dependent on their innervation by the GABAergic basket cells (BCs) and stellate cells (SCs) in the cerebellar molecular layer. The present study was designed to determine whether there are differences in the packing density of these inhibitory interneurons or whether the ratio of these interneurons to PCs differs in autistic and age-matched control brains. The GABAergic interneurons were identified by using immunohistochemistry for parvalbumin (PV) in serial sections from the posterior cerebellar lobe of six autistic and four control brains and counted using stereological principles. Prior PC counts in the same area on adjacent sections (Whitney et al., 2008) were available and were used to calculate the number of BCs and SCs per PC. In this sample of brains, no statistically significant difference was detected between the autistic and the control groups in the density of BCs or SCs (P = 0.44 and P = 0.84, respectively) or in the number of BCs or SCs per PC (P = 0.47 and P = 0.44, respectively). The preservation of BCs and SCs, in the presence of the reduced PC numbers as found in at least two, and possibly three, of these six autistic cases (Whitney et al., 2008) suggests that PCs were generated, migrated to their proper location in the PC layer, and subsequently died in the autistic cases that showed a reduction in PCs.
Subject(s)
Autistic Disorder/pathology , Cerebellum/pathology , Neurons/classification , Neurons/pathology , Purkinje Cells/pathology , Adolescent , Adult , Cell Count/methods , Female , Humans , Interneurons/pathology , Male , Middle Aged , Postmortem Changes , Young AdultABSTRACT
Although a decreased number of cerebellar Purkinje cells (PCs) in the autistic brain has been widely reported with a variety of qualitative and quantitative methods, the more accurate method of cell counting with modern stereology has not yet been employed. An additional possible problem with prior reports is the use of Nissl staining to identify the PCs, as this can miss cells due to staining irregularities. In the present study, PCs were immunostained for calbindin-D28k (CB), as this has been shown to be a more reliable marker for PCs than the Nissl stain, with more than 99% of the PCs immunopositive (Whitney, Kemper, Rosene, Bauman, Blatt, J Neurosci Methods 168:42-47, 2008). Using stereology and CB immunostaining, the density of PCs was determined in serial sections from a consistently defined area of the cerebellar hemisphere in four control and six autistic brains, with the density of PCs then correlated with the clinical severity of autism. Overall, there was no significant difference in the density of PCs between the autistic and control groups. However, three of six autistic brains had PC numbers that fell within the control range, whereas the remaining three autistic brains revealed a reduction compared with the control brains. These data demonstrate that a reduction in cerebellar PCs was not a consistent feature of these autistic brains and that it occurred without discernible correlation between their density and the clinical features or severity of autism.
Subject(s)
Autistic Disorder/genetics , Brain/pathology , Cerebellum/pathology , Purkinje Cells/pathology , S100 Calcium Binding Protein G/metabolism , Adolescent , Adult , Biomarkers/metabolism , Calbindin 1 , Calbindins , Cerebellum/physiology , Female , Humans , Male , Middle Aged , Purkinje Cells/physiology , Reference Values , Severity of Illness Index , Young AdultABSTRACT
In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortem circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker.
Subject(s)
Cerebellum/cytology , Purkinje Cells/metabolism , S100 Calcium Binding Protein G/metabolism , Staining and Labeling/methods , Adolescent , Adult , Biomarkers , Calbindin 1 , Calbindins , Female , Humans , Male , Middle Aged , Nissl Bodies , Purkinje Cells/cytologyABSTRACT
Increasing evidence indicates that the GABAergic system in cerebellar and limbic structures is affected in autism. We extended our previous study that found reduced [(3)H]flunitrazepam-labeled benzodiazepine sites in the autistic hippocampus to determine whether this reduction was due to a decrease in binding site number (B (max)) or altered affinity (K (d)) to bind to the ligand. Quantitation of hippocampal lamina demonstrated a 20% reduction in B (max) indicating a trend toward a decreased number of benzodiazepine binding sites in the autistic group but normal K (d) values. A reduction in the number of hippocampal benzodiazepine binding sites suggests alterations in the modulation of GABA(A) receptors in the presence of GABA in the autistic brain, possibly resulting in altered inhibitory functioning of hippocampal circuitry.
Subject(s)
Autistic Disorder/diagnosis , Autistic Disorder/pathology , Benzodiazepines/pharmacokinetics , Flunitrazepam/pharmacokinetics , GABA Modulators/pharmacokinetics , Hippocampus/metabolism , Hippocampus/pathology , Nerve Net/metabolism , Nerve Net/pathology , Adolescent , Adult , Autoradiography/instrumentation , Binding Sites/drug effects , Cerebellum/metabolism , Cerebellum/pathology , Humans , Male , Nissl Bodies/metabolism , Nissl Bodies/pathology , Receptors, GABA/metabolismABSTRACT
There is considerable evidence for lateralization of hippocampal function and hemispheric asymmetry in humans. In the rat, studies have reported asymmetries in the thicknesses of layers, the volumes of hippocampal subfields, and the density of cells at specific points along the septotemporal axis. To determine if there is an asymmetry of neuron numbers and whether prenatal malnutrition affects any asymmetries, 90-day old male Sprague-Dawley rats that were either normally nourished or malnourished prenatally were perfused with 4% paraformaldehyde and the brains cut into 30-micro m sections. One interrupted series of sections through the entire hippocampus was analyzed stereologically to estimate the total number of neurons in the hilus of the dentate gyrus, the CA3/CA2 stratum pyramidale (SP), the CA1 SP, and the SP of the prosubiculum/subiculum of both hemispheres. Significant asymmetries (P < 0.05) were found in the CA1 and CA3/CA2 subfields, with the right hemisphere containing 21 and 6% fewer neurons, respectively. Malnutrition reduced neuron numbers in the CA1 subfield by 12%, but did not alter the hemispheric asymmetry. Our findings agree with previous reports of left dominant asymmetries in the rat brain and suggest that this may result from differences in total numbers of neurons.
Subject(s)
Hippocampus/pathology , Malnutrition/pathology , Neurons/pathology , Prenatal Exposure Delayed Effects , Stereotaxic Techniques , Analysis of Variance , Animals , Cell Count , Female , Functional Laterality , Male , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
Infantile autism is a behaviorally defined disorder associated with characteristic cognitive, language and behavioral features. Several postmortem studies have highlighted areas of anatomic abnormality in the autistic brain. Consistent findings have been observed in the limbic system, cerebellum and related inferior olive. In the limbic system, the hippocampus, amygdala and entorhinal cortex have shown small cell size and increased cell packing density at all ages, suggesting a pattern consistent with development curtailment. Findings in the cerebellum have included significantly reduced numbers of Purkinje cells, primarily in the posterior inferior regions of the hemispheres. A different pattern of change has been noted in the vertical limb of the diagonal band of broca, cerebellar nuclei and inferior olive with plentiful and abnormally enlarged neurons in the brains of young autistic subjects, and in adult autistic brains, small, pale neurons that are reduced in number. These findings combined with reported age-related changes in brain weight and volume, have raised the possibility that the neuropathology of autism may represent an on-going process.
Subject(s)
Autistic Disorder/pathology , Brain/pathology , Neuroanatomy/methods , Forecasting , HumansABSTRACT
Malnutrition has been associated with a variety of functional and anatomical impairments of the hippocampal formation. One of the more striking of these is widespread loss of hippocampal neurons in postnatally malnourished rats. In the present study we have investigated the effect of prenatal malnutrition on these same neuronal populations, neurons that are all generated during the period of the dietary restriction. In prenatally protein deprived rats, using design-based stereology, we have measured the regional volume and number of neurons in the hilus of the dentate gyrus and the pyramidal cell layers of CA3, CA2, CA1, and the subiculum of 90-day-old animals. These results demonstrated a statistically significant reduction of 20% in neuron numbers in the CA1 subfield, while numbers in the other subfields were unchanged. There was a corresponding significant reduction of 22% in the volume of the CA1 subfield and a significant 14% decrease in the volume of the pyramidal layer of the subiculum. The change in volume of the pyramidal layer of the subiculum without neuron loss may reflect loss of CA1 afferent input to the pyramidal layer. Although the effect of nutritional deprivation on the neuronal population appears to be different in pre- and postnatal malnutrition, both dietary paradigms highlight the vulnerability of key components of the hippocampal trisynaptic circuit (consisting of the dentate granule cell mossy fibers projection to CA3 pyramids and the CA3 projection to the CA1 pyramids), which is an essential circuit for memory and learning.
Subject(s)
Fetal Nutrition Disorders/complications , Hippocampus/abnormalities , Hippocampus/pathology , Nervous System Malformations/etiology , Nervous System Malformations/pathology , Protein Deficiency/complications , Animals , Cell Count , Cell Differentiation/physiology , Cell Proliferation , Dentate Gyrus/abnormalities , Dentate Gyrus/pathology , Dentate Gyrus/physiopathology , Disease Models, Animal , Female , Hippocampus/physiopathology , Male , Mossy Fibers, Hippocampal/abnormalities , Mossy Fibers, Hippocampal/pathology , Mossy Fibers, Hippocampal/physiopathology , Nervous System Malformations/physiopathology , Neural Pathways/abnormalities , Neural Pathways/pathology , Neural Pathways/physiopathology , Neurons/pathology , Pregnancy , Pyramidal Cells/pathology , Rats , Rats, Sprague-DawleyABSTRACT
Although postnatal genesis of granule cells in the hippocampal fascia dentata is known to be influenced by prenatal protein deprivation or by stress, the combined effects of prenatal protein malnutrition and stress on these cells are unknown. This study was designed to examine this combined effect. Well-nourished and prenatally malnourished pups on postnatal day 7 (P7) were stressed by maternal separation and reduction of body temperature and on postnatal day 30 (P30) by immobilization with restraint. Bromodeoxyuridine (BrDU) was injected at the time of stress, and 2 h later, the numbers of immunolabeled cells were quantified by standard stereological techniques. In comparison to controls, prenatally malnourished rats showed a significantly lower number of cells tagged in the fascia dentata on P7 (p < or =0.05), and a significantly higher number of cells (p < or =0.05) on P30. In both age groups, control rats exposed to acute stress showed a significantly decreased number of cells tagged in the fascia dentata (p < or =0.05). In contrast, neurogenesis in malnourished rats was not significantly affected by acute stress at either age. Thus, the pattern of neurogenesis in the fascia dentata and its response to stress has been fundamentally altered by prenatal protein deprivation.
Subject(s)
Dentate Gyrus/abnormalities , Prenatal Exposure Delayed Effects , Prenatal Nutritional Physiological Phenomena/physiology , Protein Deficiency/pathology , Stress, Physiological/pathology , Acute Disease , Animals , Animals, Newborn , Cell Count , Cell Differentiation/physiology , Cell Division/physiology , Dentate Gyrus/pathology , Dentate Gyrus/physiopathology , Female , Nervous System Malformations/etiology , Nervous System Malformations/pathology , Nervous System Malformations/physiopathology , Neurons/metabolism , Neurons/pathology , Pregnancy , Protein Deficiency/physiopathology , Rats , Rats, Sprague-Dawley , Stem Cells/metabolism , Stem Cells/pathology , Stress, Physiological/physiopathologyABSTRACT
Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum.