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Timing and patterns of astrocyte migration from xenogeneic transplants of the cortex and corpus callosum.

The timing, pattern, and pathway of astrocyte migration were investigated in vivo by transplantation of CD-1 mouse cerebral cortex (E13-14) or corpus callosum (P2-3) into neonatal rat cortex. A monoclonal antibody specific for a mouse astrocyte surface antigen (M2) was used to identify the location of the grafts and the migrated donor astrocytes. Within the host cortex, astrocytes from cortical grafts began migration at post-transplantation day (PTD) 7. Over the next 4 days, the most distant displaced donor cells were found progressively further away from the grafts, migrating at a rate of about 220 microns/day. After PTD 11, the migration rate for the farthest displaced donor cells slowed to 25 microns/day, and the cells appeared to stop at about PTD 16 at a distance of 1,100 microns from the edge of the graft. Astrocytes had a faster migration speed in the white matter and covered a longer distance (5 mm) than those in the gray matter, extending on occasion into the contralateral hemisphere. The patterns of astrocyte migration differed depending on local cues around the transplant. Donor astrocytes that had been implanted into the host cortex migrated toward the host cortical surface, sometimes in several radial lines. Astrocytes from grafts, especially callosal grafts, placed in the subcortical white matter migrated along the host fiber tracts. Many astrocytes transplanted into the hippocampus formed laminar patterns close to the hippocampal neuronal layers. These results suggest that the direction, pattern, and speed of astrocyte migration are influenced by local substrates in the host brain.

Animals↗

Areal and laminar organization of corticocortical projections in the rat somatosensory cortex.

The present study examines patterns of connectivity between the primary somatosensory cortex of the rat (SI) and surrounding cortical areas also implicated in the processing of somatosensory information. The impetus for the study was the recent reports of major differences in the organization of cortex lateral and caudal to the SI in two other rodent species; the mouse (Carvell and Simons, '86: Somatosens. Res. 3:213-237; '87: J. Comp. Neurol. 265:409-427) and the grey squirrel (Krubitzer et al., '86: J. Comp. Neurol 250: 403-430). Corticocortical connections between the somatosensory areas of the rat parietal cortex were examined by using the combined retrograde and anterograde transport of horseradish peroxidase as well as the retrograde transport of fluorescent tracers. Tracer injections were made into different locations within SI and dysgranular cortex as well as into more lateral regions of parietal cortex. The tangential patterns of distribution both of callosal connections and of cytochrome oxidase activity together provided points of reference in determining the relation between injection sites and the resultant patterns of label. The results indicate that two distinct somatosensory areas, SI and the dysgranular cortex, are interconnected with a further lateral somatosensory area referred to as the second somatosensory area (SII). These projections are organized in a topographic fashion, which we interpret as evidence for a single representation of the body surface in SII. The three somatosensory areas each exhibit unique laminar patterns of ipsilateral corticocortical projection neurons and terminations. In SI, projection neurons are found mainly in layers II, III, and Va, and terminations are largely restricted to the infragranular layers. In the dysgranular cortex, projection neurons and terminations are found in all layers except layer I in which only terminal label is detectable and layer Vb in which notably fewer neurons are labelled. In SII, projection neurons and terminations are found in all layers except layer I and are particularly dense in lower layer III and layer IV. Further, whereas the laminar and areal distributions of ipsilateral and contralateral corticocortical projections largely overlap in both SI and the dysgranular cortex, in SII they tend to be areally segregated. Neurons projecting bilaterally to both ipsilateral and contralateral somatosensory cortex were equally rare in all three somatosensory areas. These results are discussed in relation to the organization of SII in other rodent species, and it is concluded that in the rat, like the mouse, cortex lateral and caudal to SI contains a single representation of the body surface.

Animals↗

Proportion of glutamate- and aspartate-immunoreactive neurons in the efferent pathways of the rat visual cortex varies according to the target.

Immunohistochemistry, with antisera directed against glutamate (Glu) or aspartate (Asp), was combined with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) histochemistry to examine the distribution, morphology, and proportions of Glu- and Asp-containing neurons that give rise to corticofugal and callosal projections of the rat visual cortex. WGA-HRP injections in the dorsal lateral geniculate nucleus resulted in retrograde labelling of small and medium-sized cells throughout layer VI of the visual cortex. Of these cells, 60% were also Glu-immunoreactive and 61% Asp-positive. WGA-HRP injections in the superior colliculus labelled large and medium-sized neurons in the upper portion of layer V of the visual cortex. Of these cells, 46% were also stained for Glu and 66% for Asp. Injections in the pontine nuclei resulted in retrograde labelling of cells in the deeper part of cortical layer V. Retrogradely labelled cells, which were also immunoreactive for Glu or Asp, were large pyramidal cells. Corticopontine neurons, which were also Glu-positive, accounted for 42% of the total number of WGA-HRP labelled cells, whilst for Asp-positive neurons this percentage was 51%. Finally, after injections in the visual cortex, retrogradely labelled small and medium-sized cells were found throughout layers II-VI in the contralateral visual cortex. Of these neurons, 38% were also labelled for Glu while 49% were also Asp-immunoreactive. The present results demonstrate that substantial proportions of projection neurons in the rat visual cortex are immunoreactive for Glu or Asp, suggesting that these excitatory amino acids are the major transmitters used by the cortical efferent systems examined. Furthermore, the proportions of these immunoreactive neurons in the efferent pathways vary according to the target.

Animals↗

Development of GABA-immunoreactivity in the neocortex of the mouse.

The prenatal and postnatal development of GABAergic elements in the neocortex of the mouse was analyzed by GABA-immunocytochemistry. Radial distribution of cells and laminar numerical densities were calculated at each developmental stage to substantiate qualitative observations. The first immunoreactive neurons were observed in the cortical anlage at embryonic day 12-embryonic day 13 (E12-E13) in the primitive plexiform layer. At following prenatal stages (E14-E19), most GABA-positive neurons were present in the marginal zone, subplate, and subventricular zone. GABA-immunoreactivity in the cortical plate appeared early (E14), although the complete maturation of its derivatives was achieved postnatally. At prenatal stages we noted a well-developed system of immunopositive fibers in the subplate. As indicated by the direction of growth cones, most of these fibers had an extracortical origin and invaded the cortex laterally through the internal capsule and striatum. In rostral and middle telencephalic levels, fibers originating in the septal region contributed to the cingulate bundle. Presumably corticofugal fibers and callosal axons were also noticed. At postnatal stages the maturation of GABA-immunoreactivity appeared to be a complex, long-lasting process, in which the adult pattern was produced at the same time as the appearance of certain regressive phenomena. Thus, between postnatal day 0 and postnatal day 8 (P0-P8), GABA-positive populations disappeared from the subventricular zone, marginal zone and to a lesser extent from the subplate. At the same ages we noticed the presence of morphologically abnormal, GABA-immunoreactive neurons in the subventricular zone and subplate which are interpreted as correlates of neuronal degeneration. Most GABA-positive subplate fibers also disappeared whereas GABA-immunoreactive axons were seen in the cingulate bundle until the adult stage. In the derivatives of the cortical plate, the maturation of GABA-immunoreactive elements progressed according to the "inside-out" gradient of cortical development, with the important exception of layer IV, which was the last layer to exhibit an adult-like appearance. Within each layer deriving from the cortical plate (layers VIa to II-III), GABA-immunoreactivity showed a protracted maturation in which the first GABA-positive cells were detected a few days after cell birth but substantial numbers of neurons began to express GABA considerably later. The later phase occurred concurrently with the maturation of GABA-positive axonal plexuses. These results suggest that different GABA-positive populations show different developmental regulation of GABA expression during cortical ontogenesis.

Aging↗

Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain.

During normal development of the mammalian forebrain, the paired cerebral hemispheres are initially separated midsagittally by the connective tissue-filled longitudinal fissure. During subsequent stages, the hemispheres fuse as basal lamina is remodeled and fibroblasts are eliminated from the fissure to create new central nervous system (CNS) territory in the midline. Two axon pathways, the corpus callosum and dorsal callosal stria, eventually use this region as part of their pathway. In order to assess the possible role of glial cells in the fusion process and in the guidance of axons in this and several other areas of the forebrain, we have analyzed the developing brain in timed cat and mouse embryos with immunohistochemical and morphological techniques. With the use of astroglial-specific antibodies and electron microscopy, we have visualized two distinct, primitive astroglial structures associated with the cerebral midline, and seven more associated with other specific brain regions. The way in which one of these structures moves as a column along the hemispheric midline in synchrony with seam formation suggests the possibility that during morphogenesis of the telencephalon, astrocytes may aid in the fusion process. In addition, the compact assemblage, early appearance and location of this and the other glial structures in relation to well defined neuroanatomical landmarks or axon pathways suggest that they may transiently compartmentalize relatively large regions of the CNS and organize certain developing fiber systems by acting as guides or barriers at critical stages of ontogeny.

Animals↗

The dorsomedial visual area of owl monkeys: connections, myeloarchitecture, and homologies in other primates.

Cortical connections of the dorsomedial visual area (DM) of owl monkeys were revealed with injections of the bidirectional tracer, wheatgerm agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the retrograde fluorescent tracer, diamidino yellow. Microelectrode recordings in two cases identified DM as a systematic representation of the visual hemifield in a densely myelinated rectangle of cortex just rostral to the dorsomedial portion of the second visual area (V-II, or area 18). Cortex was flattened and cut parallel to the surface in all cases so that the myeloarchitectonic borders of DM and other areas such as the primary visual area (V-I or area 17), V-II or area 18, and the middle temporal visual area (MT) could be readily determined, and the surface view patterns of connections could be directly appreciated. The ipsilateral pattern of connections of DM were dense and visuotopically congruent with area 17, area 18, and MT, and moderate to dense connections were with the medial visual area (M), the rostral division of the dorsolateral visual area, the dorsointermediate area, the ventral posterior area, the caudal division of inferotemporal cortex (ITc), the ventral posterior parietal area, and visuomotor cortex of the frontal lobe. The connections of DM were concentrated in the cytochrome oxidase (CO)-dense blobs of area 17, the CO-dense bands of area 18, and the CO-dense regions of MT. Callosal connections of DM were with matched locations in DM in the opposite hemisphere, and with VPP. The ipsilateral connections of DM with area 17 were confirmed by injecting WGA-HRP into area 17 in one owl monkey. In addition to labelled cells and terminals in area 18 and MT, bidirectionally transported tracer was also apparent in DM. Evidence for the existence of DM in other primates was obtained by injecting area 17 and examining the areal patterns of connections and myeloarchitecture in three species of Old World monkeys, two additional species of New World monkeys, and prosimian galagos. In all of these primates, one of three major targets of area 17 was a densely myelinated zone of cortex just rostral to dorsomedial area 18, in the location of DM in owl monkeys. Thus, it seems likely that DM is a visual area common to all primates.

Animals↗

Vibrissal stimulation affects glucose utilization in the trigeminal/somatosensory system of normal rats and rats prenatally exposed to ethanol.

The effect of gestational ethanol exposure on stimulus-induced sensory activity in the trigeminal/somatosensory system was determined. The mature offspring of mothers fed an ethanol-containing diet (Et) or pair-fed a nutritionally matched control diet (Ct) were examined. The C-row mystacial whiskers were stimulated. Glucose utilization in the principal sensory nucleus of the trigeminal nerve (PSN), ventrobasal thalamus, and somatosensory cortex was determined with [14C]2-deoxyglucose autoradiography. In Ct- and Et-treated rats, whisker stimulation increased glucose utilization in C-row barrel(oid)s in the left PSN, the right ventrobasal thalamus, and the right somatosensory cortex. The rate of glucose utilization in the C-row barrel(oid)s and in nonstimulated regions was lower in the Et-treated rats than in controls. In the cortices of Ct-treated rats, the activity in the C-row barrels on the right side was greater than in the right nonbarrel somatosensory cortex. Et-treated rats also exhibited an increase in glucose utilization, albeit smaller than that in the Ct-treated rats. In contrast, the glucose utilization in the left B- and C-row barrels of Ct-treated rats was decreased. No such decrease was evident in the left cortices of Et-treated rats. Thus, stroking whiskers stimulates the activity of sites in the trigeminal/somatosensory system. In cortex, the definition of these sites is emphasized by depressed activity, i.e., "surround" inhibition, in sites connected via callosal or corticocortical projections. Prenatal exposure to ethanol depresses the metabolic activity regardless of the physiological state; however, the "surround" inhibition of cortical activity is eliminated by prenatal exposure to ethanol through an exuberant projection.

Animals↗

Tonotopic organization, architectonic fields, and connections of auditory cortex in macaque monkeys.

Microelectrode recordings were used to investigate the tonotopic organization of auditory cortex of macaque monkeys and guide the placement of injections of wheat germ agglutinin-horse radish peroxidase (WGA-HRP) and fluorescent dyes. Anatomical and physiological results were later related to histological distinctions in the same brains after sections were processed for cytoarchitecture, myeloarchitecture, acetylcholinesterase (AchE), or cytochrome oxidase (CO). The experiments produced several major findings. (1) Neurons throughout a broad expanse of cortex were highly responsive to pure tones, and best frequencies could be determined for neurons in arrays of recording sites. (2) The microelectrode recordings revealed two systematic representations of tone frequencies, the primary area (AI) and a primary-like rostral field (R) as previously described. The representation of high to low frequency tones in A1 was largely caudorostral along the plane of the sulcus. A reversal of the order of representation of frequencies occurred in R. (3) AI and R together were coextensive with a koniocellular, densely myelinated zone that expressed high levels of AchE and CO. These architectonic features were somewhat less pronounced in R than AI, but a clear border between the two areas was not apparent. (4) Cortex bordering AI and R was less responsive to tones, but when best frequencies for neurons could be determined, they matched those for adjoining parts of AI and R. (5) Architectonically distinct regions were apparent within some of the cortex bordering AI and R. (6) The major ipsilateral cortical connections of AI were with R and cortex immediately lateral and medial to AI. (7) Callosal connections of AI were predominantly with matched locations in the opposite AI, but they also included adjoining fields. (8) Neurons in the ventral (MGV), medial (MGM), and dorsal (MGD) nuclei of the medial geniculate complex projected to AI and cortex lateral to AI. (9) Injections in cortex responsive to high frequency tones labeled more dorsal parts of MGV than injections in cortex responsive to low frequency tones.

Acetylcholinesterase↗

Cortical axon trajectories and growth cone morphologies in fetuses of acallosal mouse strains.

Hereditary absence of the corpus callosum (CC) provides an ideal experiment of nature for exploring mechanisms of axon guidance. In this study the prenatal development of CC axons in the acallosal mouse strains BALB/cWah1 and 129/ReJ or J was compared with normal hybrid mice by using the lipophilic dyes DiI and DiA. A few I/LnJ mice were also examined. The time of emergence and growth rate of CC axons from four cortical regions (frontal, parietal, temporal, occipital) were normal in acallosal strains. Their CC axons arrived at midplane on schedule but then often looped back to form the longitudinal Probst bundle. The frequency of formation of the Probst bundle was highest for axons from frontal cortex, which arrived at midplane first, and lowest for occipital axons, which arrived last. Once a few CC axons found a path to the other side via the hippocampal commissure, those that arrived later then crossed relatively normally. Some axons from the Probst bundle also managed to traverse midline in this manner. When no CC axons crossed, almost all of them entered the Probst bundle and eventually left it within a few hours to proceed in the ipsilateral white matter, never turning back toward midplane. Growth cones approaching midplane ipsilaterally and those that had crossed midline and entered contralateral white matter, as well as CC axons in the Probst bundle, expressed a normal range of size and complexity. These results demonstrate that the problem with callosal agenesis resides not in the cells of origin or the axons or growth cones themselves but in the substrates of axon guidance at the midsagittal plane.

Agenesis of Corpus Callosum↗

Human cingulate cortex: surface features, flat maps, and cytoarchitecture.

The surface morphology and cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals. Variations in surface features included a single cingulate sulcus (CS) with or without segmentation or double parallel sulci with or without segmentation. The single CS was deeper (9.7 +/- 0.81 mm) than in cases with double parallel sulci (7.5 +/- 0.48 mm). There were dimples parallel to the CS in anterior cingulate cortex (ACC) and anastomoses between the CS and the superior CS. Flat maps of the medial cortical surface were made in a two-stage reconstruction process and used to plot areas. The ACC is agranular and has a prominent layer V. Areas 33 and 25 have poor laminar differentiation, and there are three parts of area 24: area 24a adjacent to area 33 and partially within the callosal sulcus has homogeneous layers II and III, area 24b on the gyral surface has the most prominent layer Va of any cingulate area and distinct layers IIIa-b and IIIc, and area 24c in the ventral bank of the CS has thin layers II-III and no differentiation of layer V. There are four caudal divisions of area 24. Areas 24a' and 24b' have a thinner layer Va and layer III is thicker and less dense than in areas 24a and 24b. Area 24c' is caudal to area 24c and has densely packed, large pyramids throughout layer V. Area 24c' g is caudal to area 24c' and has the largest layer Vb pyramidal neurons in cingulate cortex. Area 32 is a cingulofrontal transition cortex with large layer IIIc pyramidal neurons and a dysgranular layer IV. Area 32' is caudal to area 32 and has an indistinct layer IV, larger layer IIIc pyramids, and fewer neurons in layer Va. Posterior cingulate cortex has medial and lateral parts of area 29, a dysgranular area 30, and three divisions of area 23: area 23a has a thin layer IIIc and moderate-sized pyramids in layer Va, area 23b has large and prominent pyramids in layers IIIc and Va, and area 23c has the thinnest layers V and VI in cingulate cortex. Area 31 is the cinguloparietal transition area in the parasplenial lobules and has very large layer IIIc pyramids. Finally, variations in architecture between cases were assessed in neuron perikarya counts in area 23a. There was an age-related decrease in neuron density in layer IV (r = -0.63; ages 45-102), but not in other layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Mapping↗

Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices.

The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of Alzheimer's disease. The present results support the hypothesis that neurofilament protein may be crucially linked to the development of selective neuronal vulnerability and subsequent disruption of corticocortical pathways that lead to the severe impairment of cognitive function commonly observed in age-related dementing disorders.

Animals↗

Prenatal disturbance alters the size of the corpus callosum in young monkeys.

Many factors during fetal life and early infancy have been found to affect the development of the brain. The following study investigated whether maternal stress during pregnancy would influence the size and shape of one sensitive brain region, the corpus callosum, in infant monkeys. For 30% of the gestation period, from Days 90 to 140 postconception, gravid females were disturbed using an acoustical startle protocol for 10 min per day. Magnetic resonance imaging was then employed to obtain sagittal and coronal scans of their infants' brains. Morphometric measures of the corpus callosum were compared in 16 monkeys (5 controls and 11 from disturbed pregnancies). Prenatal conditions altered the corpus callosum, but in a differential manner for male and female monkeys. Based on the midsagittal and parasagittal scans, prenatally disturbed male offspring showed a decrease in overall size of the corpus callosum whereas the prenatal disturbance resulted in an increased area in females. An evaluation of callosal height from the coronal images suggested that the volumetric change was associated with a shift in anterior-to-posterior shape from the genu back toward the splenium. These findings concur with observations in other animals and humans, which have indicated that prenatal and postnatal factors can influence the development of the corpus callosum, possibly affecting communication between the hemispheres.

Agenesis of Corpus Callosum↗

The effects of intrauterine position on the degree of corpus callosum deficiency in two substrains of BALB/c mice.

Measures of several intrauterine position variables as well as an index of abnormality of fetal commissure development (z score) were obtained for fetuses of two substrains of BALB mice, BALB/cWah1 and BALB/cWah2, known to differ as adults in the proportion of animals exhibiting deficient corpus callosum (about 55% & 20% respectively). The extent of midline commissure development at embryonic Day 17.5 for most strain 1 fetuses was significantly reduced compared to strain 2 fetuses of the same chronological age. The two substrains also differed with respect to mean litter size and mean body weight (strain 2 greater than strain 1 for both measures). The ovarian and cervical positions for strain 2 uteri were found to be the most favorable for body and placental growth; no such differences were evident in strain 1. In strain 2, fetuses in the left uterine horns showed lower z scores (more retardation) than littermates on the right side, but this difference was not evident in strain 1; no other right/left differences were found in strain 2 which could help to explain the right side advantage. None of the other position variables either separately or in combination was found to be important in predicting the z score index. Tests for randomness failed to provide evidence for nonrandom distribution of severely affected fetuses. We suggest that nongenetic variability resulting from stochastic events early in development and intrinsic to the fetus may be responsible for only certain BALB fetuses within a litter exhibiting the callosal anomaly.

Agenesis of Corpus Callosum↗

A qualitative and quantitative study of the glial cells in normal and athymic mice.

A qualitative and quantitative light and electron microscopic analysis of the glial cells in the supraventricular part of the corpus callosum of the neonatal and adult homozygous athymic nude (nu/nu) and normal BALB/c (+/+) mice was carried out to determine the possible contribution of nude gene mutation to glial cell development. Quantitative cell counts using toluidine blue stained serial callosal sections of 0.5 micron thickness showed that the overall glial cell population was significantly reduced in both neonatal and adult athymic mice. The number of glioblasts, astrocytes and microglia of 5-day-old athymic mouse was reduced by 10%, 27%, and 39%, respectively, when compared to the 5-day-old normal mouse. The frequency of necrotic cells in the neonatal athymic mouse increased by 70% when compared with the normal mouse. In the 13-week-old adult athymic mouse, the number of oligodendrocytes, astrocytes, and microglia decreased by 19%, 31%, and 33%, respectively, when compared to normal mouse. There was no significant difference in the area covered by the corpus callosum in 5-day-old and adult nude mice versus the normal ones of corresponding ages. Except for microglia and astrocytes, the ultrastructural features of the other glial cell types in both strains were comparable. Most of the microglial cells of the neonatal normal mouse were round and were selectively marked by Mac-1 monoclonal antibody at their plasma membrane. The immunoreactivity appeared to be more intense in the normal than the athymic mouse, suggesting a down regulation of CR3 receptors and reduced phagocytic activity of this cell type in the athymic mouse. It is proposed that the increased number of necrotic cells in the neonatal athymic mouse may be attributed to the delay in the removal of dead cells normally phagocytosed by microglia. The microglia in both strains of mouse showed comparable lectin staining intensity at the plasma membrane, indicating that their glycoprotein binding receptors to lectin remained unchanged. Some astrocytes in the adult athymic mice showed hypertrophy. The reduced number of glial cells may be the direct result of genetic mutation or consequential to the lack of certain trophic factors arising from the genetic mutation. Thus, the reduction of microglial cells in both neonatal and adult athymic mice may be due to the lack of thymic hormones which, together with lymphokines have been shown to affect the maturation of bone marrow-derived cells including monocytes, the putative precursor cells of microglia. The reduction in the number of glioblasts and astrocytes may be attributed to the diminution of T lymphocytes or consequential to the reduction of microglia which are known to secrete interleukin-1 that would influence gliogenesis and produce specific growth factors for promoting astrocyte proliferation. Last, as interaction exists between astrocytes and oligodendrocytes, the products of astrocytes may affect the development of oligodendrocytes and vice vasa. The present findings point to a relation between glial cell development and immune network system.

Animals↗

Bilateral cortical representation of the trunk midline in human first somatic sensory area.

The cortical representation of the trunk zone in the human first somatosensory area was studied with functional magnetic resonance imaging (fMRI) to establish whether the cutaneous regions close to the midline are represented in this area of both hemispheres. Cortical activation foci evoked by unilateral tactile stimulation of ventral trunk regions were detected in the postcentral gyrus of the contralateral hemisphere slightly medial to or just behind the omega-shaped region of the central sulcus and in the anterior bank of the postcentral sulcus. These regions probably correspond to the trunk ventral midline representation zones of areas 3a-3b and 1-2, respectively. Stimulation of cutaneous regions adjacent to the midline evoked activation foci also in the ipsilateral postcentral gyrus in regions symmetrical to those activated in the contralateral hemisphere. These data demonstrate that in humans, as in nonhuman primates, the cutaneous regions adjacent to the trunk midline are represented bilaterally in the first somatic sensory cortex. Whether the ipsilateral activation depends on callosal or extracallosal inputs remains to be elucidated.

Abdomen↗

Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment.

Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories.

Aged↗

Migratory patterns of lac-z transfected human glioma cells in the rat brain.

Malignant brain tumors are characterized by extensive tumor-cell infiltration into the normal brain tissue. The present work describes the migratory behavior of human glioma cells transplanted into the adult rat brain with the aim of exploiting the extent of active cell migration and passive cell displacement within the central nervous system. To detect every transplanted tumor cell, a stably bacterial beta-galactosidase (lac-z) transfected human glioma cell line was used. To distinguish between an active cell migration process and passive cell displacement, rat brains were also implanted with inert fluorescent polystyrene microspheres and the distribution of tumor cells and microspheres was studied 1 hr and 3 days after implantation. One hour after implantation the tumor cells were strictly localized at the implantation site. However, 3 days after implantation, both tumor cells and microspheres showed an extensive distribution within the brain. Confirming earlier neuropathological and experimental studies, it is shown that the lac-z-transfected glioma cells had the capacity to move within the Virchow-Robin and subarachnoid spaces. However, since fluorescent microspheres were also found in these areas, this spread of tumor cells may be primarily mediated by the extensive cerebrospinal fluid flow that exists within the brain. Three days after implantation, the glioma cells also showed an active migration over the corpus callosum. In comparison, the fluorescent microspheres showed only limited spread along the callosal body. It is concluded that the bacterial lac-z gene can be stably transfected into human glioma cells and, since every tumor cell can be visualized within the brain, this model provides a tool for studying the mechanisms behind tumor-cell invasion of the brain.

Animals↗

Immunocytochemistry of plant defense mechanisms induced upon microbial attack.

During the past few years, cyto- and immunocytochemical techniques have been developed and widely used for locating and identifying various molecules in plant cell compartments. The last decade has witnessed tremendous improvements in molecular cytology, thus allowing an accurate in situ detection of various components thought to play important biological functions in the plant metabolism. The use of immunocytochemistry to investigate resistance mechanisms of plants upon pathogen attack has provided key information on the defense strategy that plants elaborate during a host-pathogen interaction. Of the various proteins induced in response to infection, chitinases and beta-1,3-glucanases have been the focus of particular attention due to their believed antimicrobial activity through the hydrolysis of the main fungal wall components, chitin and beta-1,3-glucans. Attention has also been paid to beta-fructosidase, the enzyme that hydrolyzes sucrose into glucose and fructoside. The marked accumulation of this enzyme upon pathogen infection has led to the consideration that infection may greatly influence the metabolic activity of colonized tissues by creating alterations of source-sink relationships. Another facet of the plant's defense strategy that has been the focus of considerable interest is related to the accumulation of structural compounds, such as hydroxyproline-rich glycoproteins and callose, to reinforce the wall architecture, thus decreasing vulnerability to microbial enzymes. A number of alternatives designed to improve plant protection towards pathogen invasion have been suggested. Among these, the production of transgenic plants expressing constitutively a foreign resistance gene and the pretreatment of plants with elicitors of defense reactions have been the subject of intensive studies at the molecular, biochemical, and cytological levels. Results of such studies clearly demonstrate the important contribution that cyto- and immunocytochemical approaches can make to our knowledge of how plants defend themselves and how plant disease resistance can be directly enhanced. These approaches will undoubtedly be active areas for future research in the development of biological control alternatives in which the mode of action of the product used is of key importance.

Bacteria↗