Programmed cell death: the paths to suicide.
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Animals↗
Biomedical subjects
J Altman
Publications and source records attributed to J Altman.
Effect of cyclooxygenase blockade on blood flow through well-developed coronary collateral vessels.
Collateral vessels that develop after coronary artery occlusion demonstrate perivascular inflammation, subintimal hyperplasia, and endothelial proliferation. This study was performed to test the hypothesis that these abnormalities are associated with evidence for increased production of vasodilator prostaglandins. Eight dogs were studied 4-6 months after occlusion of the anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study, the anterior descending coronary artery was cannulated at the site of occlusion to allow measurement of retrograde blood flow as an index of interarterial collateral flow. Injection of radioactive microspheres during the retrograde flow collection allowed determination of continuing tissue flow in the collateral-dependent zone as an index of intramural microvascular collateral flow. Retrograde and tissue flows were measured before and 20 minutes after 5 mg/kg i.v. indomethacin, a dose that caused 95 +/- 3% inhibition of the coronary vasodilation in response to a 500 micrograms intracoronary bolus of arachidonic acid. Heart rate and mean aortic pressure were not significantly altered by indomethacin, and blood flow to the normally perfused myocardial region was not changed by administration of indomethacin. However, indomethacin caused a 40 +/- 7% decrease in retrograde flow (p less than 0.01), and microvascular collateral flow to the dependent myocardium decreased by 20 +/- 10% (p less than 0.05). These data indicate that, unlike the normal coronary circulation, well-developed coronary collateral vessels are under the tonic influence of vasodilator prostaglandins.
Animals↗
Planar differences in nuclear area and orientation in the subventricular and intermediate zones of the rat embryonic neocortex.
Nuclear area and orientation in the subventricular and intermediate zones was studied quantitatively in coronal vs. sagittal sections of the dorsomedial neocortex. Nissl-stained methacrylate-embedded normal rat embryos were studied between embryonic days (E) 13 and E22. The area of nuclear profiles and the degrees their long axes (defined as a straight line through the two most distant points in the nuclear profile) deviated from the horizontal (defined as parallel to the pial membrane) were determined with a computer-graphics program. Because the nucleus is the most clearly outlined structure in embryonic cells, the area and orientation of the nucleus was taken to reflect the overall size and orientation of the cell body. Nuclear area is larger in the coronal plane than it is in the sagittal plane, especially between E17 and E20. Cell body orientation in the subventricular and lower intermediate zones is predominantly horizontal in the coronal plane and predominantly vertical in the sagittal plane. In the upper intermediate zone, cell body orientation is predominantly vertical in both planes, but more so in the sagittal plane. These data indicate that the majority of cell bodies in the subventricular and lower intermediate zones have a horizontally oriented, flattened elliptical shape with their larger diameters lying within the coronal plane and their smaller diameters in the sagittal plane. Because of the flattening, the cell bodies falsely appear to be vertically oriented in the sagittal plane. Qualitative observations in horizontal sections confirmed the quantitative computer analysis. These results are related to other findings with [3H]thymidine autoradiography concerning cell migration and the sojourn of cells in the subventricular and intermediate zones.
Animals↗
Cell migration in the rat embryonic neocortex.
Three-dimensional reconstructions of the normal rat embryonic (E) neocortex on days E15, E17, E19, and E21, using Skandha (software designed by J. Prothero, University of Washington, Seattle), show that the neocortical ventricular zone shrinks rapidly in the medial direction during cortical morphogenesis. [3H]thymidine autoradiography indicates that the shrinkage of the ventricular zone occurs before neurons in lateral and ventrolateral parts of layers IV-II are generated. Consequently, most of these neurons originate 400-1000 microns medial to their settling sites in the cortical plate. Embryos killed at daily intervals up to E21 after a single injection of [3H]thymidine on either E17 or E18 revealed the presence of a prominent migratory path, the lateral cortical stream, used by neurons migrating to the lateral and ventrolateral cortical plate; neurons migrating to the dorsal cortical plate follow a direct radial path. Arrival times of neurons in the cortical plate depend on the migratory path and are proportional to the overall distance travelled. Neurons that migrate only radially arrive in the dorsal cortical plate in two days (shortest route). Neurons that migrate laterally arrive in the lateral cortical plate in 3 days (longer route) and in the ventrolateral cortical plate in 4 days (longest route). [3H]thymidine autoradiography also shows that cells generated in the neocortical ventricular zone migrate in the lateral cortical stream for 5 or more days and accumulate in a reservoir. Cells leave the reservoir to enter the piriform cortex and destinations (as yet undetermined) in the basal telencephalon. The lateral cortical stream is found wherever the neocortical primordium surrounds the basal ganglia and is absent behind the basal ganglia. A computer analysis of nuclear orientation in anterior and posterior parts of the intermediate zone in the dorsal neocortex between days E17 and E22 shows that horizontally oriented nuclei are more common anteriorly where many cells are migrating laterally than posteriorly where most cells are migrating radially.
Animals↗
Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies.
We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis.
Angiography↗
Development of the endopiriform nucleus and the claustrum in the rat brain.
Long-survival [3H]thymidine autoradiography was used to quantitatively determine the time of origin of neurons in the endopiriform nucleus and the claustrum in rats killed on postnatal day 60 after their dams received two consecutive daily injections of [3H]thymidine on embryonic day E13 and E14, E14 and E15, ... E21 and E22. The claustrum originates late, on E15 and E16, and has a strong gradient in the longitudinal direction, posterior (older) to anterior (younger). In contrast, the endopiriform nucleus originates early, on E14 and E15, and lacks a longitudinal gradient but has a strong one in the vertical direction, ventral (older) to dorsal (younger). Sequential-survival [3H]thymidine autoradiography was used to qualitatively determine the germinal sources and settling sites of endopiriform and claustral neurons in embryonic rats. The dams received a single injection of [3H]thymidine on either E14 (to heavily label older endopiriform neurons) or E16 (to heavily label younger claustral neurons) and were killed in sequential 24-h intervals. Neurons in the presumptive endopiriform nucleus settle within two to three days after their peak time of neurogenesis while those in the presumptive claustrum take approximately five days to settle after their peak. It is postulated that endopiriform neurons are generated in the palliostriatal ventricular angle, the neuroepithelium that forms a wedge between the primordia of the neocortex and the basal ganglia, and that claustral neurons are generated in the neocortical neuroepithelium. Divergent developmental patterns between the endopiriform nucleus and the claustrum support the anatomical evidence that these nuclei have different connections. Furthermore, neurogenetic gradients in the claustrum correlate with the pattern of anatomical connections between the claustrum and the neocortex.
Animals↗
Development of the diencephalon in the rat. IV. Quantitative study of the time of origin of neurons and the internuclear chronological gradients in the thalamus.
Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 13 and 14 (E13 + 14) until the day before birth (E21 + 22). With this progressively delayed comprehensive labelling procedure we determined the time of origin of neurons in the nuclei of the epithalamus, thalamus, and ventral thalamus. The zona incerta, subthalamic nucleus, reticular nucleus, posterior nucleus, and ventral lateral geniculate nucleus are composed of the earliest arising neurons (E13, or before, to E15). The neurons of the lateral habenular nucleus are produced between days E13--16. The neurons of the medial geniculate and lateral geniculate nuclei, the ventrobasal and ventrolateral complexes, and the nucleus lateralis, pars posterior, arise rapidly on days E14--15; the medial geniculate nucleus with a peak on day E14, the others with a peak on day E15. Neurons of a group of nuclei, with ill-defined boundaries medial to the sensory relax nuclei, arise apparently on days E15--16, with a peak on day E15; these may represent the intralaminar nuclei. The next group is generated on days E15--16 but with peak formation time on day E16; this includes the anteroventral, anterodorsal, anteromedial and mediodorsal nuclei. The rhomboid, reuniens and paratenial nuclei, and the paraventricular nucleus, pars anterior, arise next (E16--17). The medial habenular nucleus forms last and over a protracted period (E15--19). With their lengthy generation time the lateral and medial habenular nuclei resemble more the nuclei of the hypothalamus than the nuclei of the dorsal thalamus.
Animals↗
Development of the diencephalon in the rat. V. Thymidine-radiographic observations on internuclear and intranuclear gradients in the thalamus.
Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 13 and 14 (E13 + 14) until the day before birth (E21 + 22). Internuclear and intranuclear cytogenetic gradients were examined in radiograms of the thalamus sectioned in the coronal, sagittal and horizontal planes. There was a precise and segregated lateral-to-medial gradient between and within the habenular nuclei. In the ventral thalamus the reticular nucleus had a lateral-to-medial gradient, the subthalamic nucleus a laterodorsal-to-medioventral gradient. There was a caudal-to-rostral gradient between the medial geniculate and dorsal lateral geniculate nuclei, and between the pars posterior and pars anterior of the lateral nucleus. A clear intranuclear gradient could not be detected in the sensory relay nuclei with the exception of the medial geniculate nucleus. A lateral-to-medial internuclear gradient was seen between the relay nuclei and the intralaminar nuclei, and between the latter and some of the midline nuclei. On the basis of a consideration of the time of origin and time span of production of neurons of various thalamic nuclei, and taking into account some of the recognizable internuclear and intranuclear gradients, the thalamus was divided into five principal cytogenetic components; the epithelamus, the ventral thalamus, the dorsal thalamus, the medial thalamus, and the posterior thalamus. The epithalamic nuclei form over a protracted period resembling the nuclei of the hypothalamus. The nuclei of the ventral thalamus are generated early and over a relatively long period. The dorsal thalamus consists of the relay nuclei and the intralaminar nuclei; they form rapidly and ahead of the medial thalamus. The medial thalamus was subdivided into the earlier-forming anteromedial nuclei and the latest-forming midline nuclei. The posterior thalamus was not examined in detail.
Animals↗
Development of the diencephalon in the rat. VI. Re-evaluation of the embryonic development of the thalamus on the basis of thymidine-radiographic datings.
The development of the thalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The differentiating, radioresistant neurons of the lateral habenular nucleus, derived from a portion of the superior neuroepithelial lobule (SL1), were settling by day E15 and by this time the habenulopeduncular tract was forming. The neurons of the reticular nucleus, derived from the middle neuroepithelial lobe, began to settle on day E15 but a massive migration was still evident on day E16. Adjacent to the reticular nucleus the internal capsule appeared on day E16; this fiber bundle seemed to be continuous with fibers embedded in the first transitory zone of cells issuing from the dorsal neuroepithelial lobe. Because of the immaturity of the neocortex at this time, it was postulated that thalamocortical fibers of the dorsal thalamus are the earliest components of the internal capsule. By day E17 all the sensory relay nuclei of the thalamus were recognizable and it was assumed that the second transitory zone issuing from the receding dorsal neuroepithelial lobe contained the neurons of the later forming intralaminar nuclei. Suggestive evidence was obtained that the late arising neurons of the medial thalamus (the anterior nuclei, the mediodorsal nucleus, and some or all of the midline nuclei) originate in a portion of the superior neuroepithelial lobule designated as SL2. Our present and previous studies showed that the major divisions of the hypothalamus and thalamus are derived embryonically from distinguishable parts of the third ventricle neuroepithelium. This implies the te third ventricle neuroepithelium has a "mosaic" organization and suggests that the fate of hypothalamic and thalamic neurons may be determined to some extent while their precursors are still proliferating.
Animals↗
Effects of differential interference with postnatal cerebellar neurogenesis on motor performance, activity level, and maze learning of rats: a developmental study.
The region of the cerebellum was X-irradiated in infant rats with selected exposure schedules designed to produce animals in which the cerebellar cortex was (a) essentially normal except for agenesis of late forming granule cells with axons situated in the uppermost molecular layer (12--15X), (b) lacking in stellate cells, with a severe reduction in granule cells with axons in the upper molecular layer (8--15X), (c) morphologically disorganized but had only intermediate cell agenesis (4--5X), or (d) disorganized and devoid of practically all postnatally forming interneurons (4--15X). In the first two experiments young adults had to traverse rotating rods that differed in texture and types of obstacles. The 8--15X animals showed no deficits on any of the rods tested. The third study dealt with spontaneous motor performance in the open field at three ages. The 4--5X and 4--15X animals were hypoactive as infants and young adults; this was attributed to their motor deficits. The 8--15X and 12--15X animals were hyperactive in the open field as young adults. The fourth experiment examined intra- and/or intersession habituation. No group differences were found in habituation patterns. In the fifth experiment, using activity wheels, the 4--15X group was hypoactive, and the 8--15X and 12--15X groups were hyperactive as young adults. In the sixth experiment young adults were tested for learning performance in a multiple-unit water maze. The 4--15X group was deficient on single alternation; the 4--5X and 12--15X groups on double alternation. The seventh experiment shed some light on the single alternation deficit of the 4--15X group; only these animals failed to alternate spontaneously in a nonaversive situation. In conclusion, these behavioral results, combined with those of recent morphological investigations, suggest that the cerebellar cortex is hierarchically organized: The basal domain of Purkinje cells and the lower molecular layer are implicated in the coordination of movements; the apical domain of Purkinje cells and the upper molecular layer, in the coordination of actions.
Animals↗
The postnatal development of the main olfactory bulb of the rat.
The postnatal development from birth to 1 year of the main olfactory bulb was examined quantitatively. The volume of the main olfactory bulb increased over seven-fold by day 30 and remained unchanged thereafter. During the same period the volume of the granular layer increased 18-fold and the mean areas of the olfactory glomeruli increased seven-fold. The mean areas of mitral cell perikarya doubled between the neonatal and juvenile periods. The total number of the mitral cells, however, declined during the first three postnatal weeks. In the internal granular layer of the main olfactory bulb, 89% of the granule cells were acquired postnatally. Much of the cellular gain occurred during the first 3 weeks, with the period of maximum acquisition between days 8 and 14. The number of subependymal cells, the precursors of granule cells, reached a peak at 12 days and gradually declined. But some primitive cells could still be found at one year of age and there was an increase in the total number of granule cells beyond day 30. The mean nuber of internal granular layer cells in a single main olfactory bulb of adult rats was about 5 X 10(6); the number of mitral cells about 4 X 10(4). In the animals injected with 3H-thymidine on day 20 and killed 2 h after injection a small but significant proportion of cells was labelled in the subependymal layer but few in the internal granular layer. In the animals killed 20 and 40 days after injection there was a 10--11-fold rise in the proportion of labelled internal granular layer cells. The proportion of labelled internal granular layer cells decreased in longer survival groups but the total number of labelled cells remained the same, even in year-old animals. However, the total number of internal granular layer cells in the sections examined increased with age.
Aging↗
Development of the diencephalon in the rat. I. Autoradiographic study of the time of origin and settling patterns of neurons of the hypothalamus.
Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day 13 (E13 + 14) until the day before birth (E21 + 22). This double labelling procedure was combined with an injection schedule of a single day delay between groups (E13 + 14; E14 + 15; E15 + 16 . .). The two injections assured the comprehensive labelling of practically all neurons of a given structure prior to the onset of their differentiation (comprehensive labelling), whereas the progressive daily delay in injections made it possible to estimate the proportion of neurons formed in various regions of the hypothalamus on a single day. Hypothalamic areas or nuclei were assigned into four classes on the basis of their cytogenetic isochronicity. Structures composed of the earliest arising (class 1) neurons constitute a lateral tier that includes the lateral preoptic and lateral hypothalamic areas, and the lateral mammillary nucleus. Structures composed of early arising (class 2) neurons form a heterogeneous collection of nuclear systems, including the paraventricular, internuclear and supraoptic magnocellular neurons, and several intermediate tier nuclei of the anterior and posterior hypothalamus. The late arising (class 3) and latest arising (class 4) nuclei constitute a periventricular system anteriorly and a more extensive region posteriorly. The latter two nuclear systems may constitute the hypophysiotropic area of the hypothalamus. The nuclei of the mammillary system, which are produced sequentially, are distinguished from other hypothalamic structures by their more rapid generation time. Internuclear labelling gradients were used to infer the neuroepithelial site of origin and settling pattern of neurons. Common sites of origin were indicated for the following structures: the magnocellular neurohypophysial neurons; the neurons of the dorsomedial and ventromedial nuclei; and the neurons of the tubermammillary and arcuate nuclei. The sites of origin of these groups of nuclei were related to specialized ventricular linings in the mature hypothalamus.
Animals↗
Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons.
The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuroepithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at this site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.
Animals↗
Development of the diencephalon in the rat. III. Ontogeny of the specialized ventricular linings of the hypothalamic third ventricle.
The development of the specialized linings of the hypothalamic third ventricle was examined autoradiographically in mature rats that were labelled with 3H-thymidine during the developmental period, and in a closely spaced series of embryonic and infant rats. We distinguished in mature rats, apart from the typical ependymal wall, three specialized linings: the convoluted ependyma, the laminated epithelium, and the tanycytic epithelium. The ventricular wall of most of the anterior hypothalamus, and of the dorsal portion of the posterior hypothalamus, is composed of ciliated ependymal cells and most of them are generated several days before birth, soon after the cessation of neurogenesis in the adjacent hypothalamic nuclei. The cells of the rostral convoluted ependyma adjacent to the paraventricular nucleus are produced at about the same time as the neighboring cells of the smooth ependyma. Its cells come from the same germinal region that we have assumed to generate the neurons of the magnocellular neurohypophysial secretory system. The structural differentiation of the convoluted ependyma starts after birth and is completed by the beginning of the second week. Many of the ependymal cells of the laminated epithelium are produced postnatally, and the production of the specialized cells that form a parallel subependymal row extends into the third week. These cells appear to arise from the same matrix that generates earlier the neurons of the dorsomedial and ventromedial hypothalamic nuclei; their structural differentiation begins during the second week. Also the cells of the tanycytic epithelium are produced mostly postnatally, predominantly during the first week. They appear to arise from the same matrix that generated earlier the neurons of the hypophysiotropic tuberomammillary and arcuate nuclei. It is postulated that these three specialized ventricular linings are specifically related to the three cpmponents of the endocrine hypothalamus with which they have shared neuroepithelial sites of origin.
Animals↗
Speckled lentiginous nevus.
Speckled lentiginous nevus is, we feel, a distinctive nevocytic disorder and a clinical variety of nevus-cell nevus. The speckled areas show varying histological patterns that range from nevus incipiens to junctional and compound nevi. The background shows histological features of lentigo simplex. It is our contention that speckled lentiginous nevus should be separated from nevus spilus and nevus spilus tardus (Becker's), which we consider to be variants of epidermal nevus.
Adolescent↗
Time of origin and distribution of a new cell type in the rat cerebellar cortex.
A new cell type was identified in the granular layer of the rat cerebellum. It has a lightly staining nucleus with a nucleolus, it is spherical in shape and is larger than granule cells and smaller than Golgi cells. These pale cells are preferentially concentrated in the nodulus, the ventral uvula, the lingula, the flocculus, and parts of the paraflocculus. According to autoradiographic (3H-thymidine) evidence, over 60% of these pale cells are formed on embryonic days 19 and 20, and their production comes to an end soon after birth, prior to the differentiation of granule cells. The possible relation of pale cells to vestibular afferents of the cerebellar cortex is discussed.
Animals↗
The effect of ethanol chronically administered to preweanling rats on cerebellar development: a morphological study.
The effects of ethanol on body, brain and cerebellar growth of the postnatal rat have been studied. Vapor inhalation, the procedure used to administer ethanol directly to preweanling (3-20-day-old) rats, produced maximal blood ethanol levels that averaged 239 mg/100 ml. Weight determinations indicated that brain but not body growth was significantly stunted by exposure to ethanol. Moreover, cerebellar growth, which occurred largely but not wholly during the period of ethanol treatment, was inhibited twice as much as the rest of the brain. Arrested brain and cerebellar growth appeared shortly after ethanol treatment was begun and persisted into adulthood following a postweaning rehabilitation period. Ethanol treatment diminished the growth of both the anterior and posterior lobes and of all layers of the cerebellar vermis. However, the effect of ethanol was larger in the anterior lobe than the posterior lobe, and the medullary layer was more retarded than the others. Some compensatory growth occurred in the molecular and granular layers of the experimental rats during a postweaning rehabilitation period. The effects of ethanol on 2 major neuronal populations of the cerebellar cortex -- the large, prenatally-formed Purkinje cells and the small, postnatally-formed granule cells -- were assessed via light microscopy. After 2 days of ethanol treatment the number of Purkinje cells in all 10 vermal lobules was reduced; neither additional exposure to ethanol nor a postweaning rehabilitation period subsequently altered cell number. The possibility that the regional magnitude of the Purkinje cell loss was related to the chronology of lobular development was discussed; Purkinje cells in the latest maturing lobules being least affected. The morphological development of surviving Purkinje cells proceeded normally. An autoradiographic study indicated the pattern of granule cell neurogenesis in cerebella of ethanol-treated rats and of control rats did not differ, although the experimental animals had consistently fewer cells in all stages of development. The ultimate loss of 20-25% of their granule cells was accounted for by an early diminution of the stem cell population of the external germinal layer by about 10%. The results suggest the initial targets of ethanol were the immature Purkinje cells, which were reduced in number before the onset of granule cell formation. A complex age-dependent interaction between blood ethanol levels and vulnerable periods in Purkinje cell development was suggested. Mechanisms for the subsequent correlative reduction in the granule cell population were also discussed.
Age Factors↗
Postnatal development of the cerebellar cortex in the rat. V. Spatial organization of purkinje cell perikarya.
The development of the spatial organization of Purkinje cell perikarya was examined in the rat cerebellum from birth to adulthood. Dispersion of the perikarya following birth is made possible by the rapid expansion of the cortical surface. Their subsequent regular monocellular alignment is ensured by mechanical factors, the pressure exerted from below by the expanding granular layer and the barrier formed above by the pile of parallel fibers which prevent the penetration of the bulky perikarya into the molecular layer. The perikarya remain in this position even after the slender stem dendrite pierces the molecular layer along the descending axons of basket cells. The increase in interperikaryal distance between Purkinje cells is rapid up to day 12, then declines. This is temporally associated with the growth of the basket cell plexus and glial envelope around the perikaryon. The increase in perikaryal size continues up to day 30. This may be temporally associated with the growth of the Purkinje cell dendritic arbor as reflected by the expansion of the molecular layer up to day 30. The spatial arrangement of Purkinje cells within the monocellular sheet was graphically displayed with computer aid. In the adult cerebellum a hexagonal arrangement could be recognized in a proportion of "near-neighborhoods," consisting of about six Purkinje cells and their neighbors. When the neighborhoods were extended with fixed orientation with respect to the axis of the folium, the hexagonal arrangement disappeared. When orientation was ignored, the superimposed near-neighborhoods could be rotated to produce a hexagonal pattern. In the infant cerebellum the hexagonal arrangement could not be demonstrated before the alignment of Purkinje cells in a monolayer. Thereafter there appeared to be an increase with age in the proportion of hexagonally arranged near-neighborhoods. It was concluded that in the monocellular ganglionic layer Purkinje cells are not aligned in regular rows with respect to the geometrically arranged elements of the supraganglionic layer. The formation of an imprecise hexagonal pattern, like the alignment of Purkinje cells in a monolayer, was attributed to mechanical factors.
Age Factors↗