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PubMed1982

[A further role on the structuro-functional organization of the vegetatovisceral manifestations of epilepsy (diencephalic epilepsy?)].

The authors present the results of examining 138 patients whose disease could be classed with the so-called "diencephalic epilepsy" proceeding from the structure of the paroxysmal vegetovisceral manifestations, the degree of the neuroendocrinal syndromes, the complicate scope of the organic and functional anomalies, and hydrocephalus of the IIId ventricle. Stereoelectroencephalographic examinations made in the course of spontaneous vegetovisceral and polymorph seizures have shown that the aura correlates with the reaction of desynchronization in the deep and cortical structures of the brain; the specific manifestations of the seizures are combined with epileptic discharges in the limbic and neocortical structures and absence of the discharges in the thalamus and hypothalamus. It has been shown that the limbic system, the neocortical and truncal divisions of the brain take part in the structural and functional organization of the vegetovisceral paroxysms. It is supposed that the hypothalamus plays a non-specific role in the realization of the vegetovisceral paroxysms. On the basis of recognizing the system organization of epileptic process the authors cast doubt on the term "diencephalic epilepsy".

Adolescent↗

PubMed2005

Electroencephalographic response to transcranial magnetic stimulation in children: Evidence for giant inhibitory potentials.

The electroencephalographic response to transcranial magnetic stimulation (TMS) recently has been established as a direct parameter of motor cortex excitability. Its N100 component was suggested to reflect an inhibitory response. We investigated influences of cerebral maturation on TMS-evoked N100 in 6- to 10-year-old healthy children. We used a forewarned reaction time (contingent negative variation) task to test the effects of response preparation and sensory attention on N100 amplitude. Single-pulse TMS of motor cortex at 105% motor threshold intensity evoked N100 amplitudes of more than 100 microV in resting children (visible in single trials), which correlated negatively with age and positively with absolute stimulation intensity. During late contingent negative variation, which involves preactivation of the cortical structures necessary for a fast response, N100 amplitude was significantly reduced. We conclude that (1) N100 amplitude reduction during late contingent negative variation provides further evidence that TMS-evoked N100 reflects inhibitory processes, (2) response preparation and attention modulate N100, and (3) TMS-evoked N100 undergoes maturational changes and could serve to test cortical integrity and inhibitory function in children. Parallels between the inhibitory N100 after TMS (provoking massive synchronous excitation) and the inhibitory wave component of epileptic spike wave complexes are suggested.

Adult↗

PubMed1995

Neuromodulation and cortical function: modeling the physiological basis of behavior.

Neuromodulators including acetylcholine, norepinephrine, serotonin, dopamine and a range of peptides alter the processing characteristics of cortical networks through effects on excitatory and inhibitory synaptic transmission, on the adaptation of cortical pyramidal cells, on membrane potential, on the rate of synaptic modification, and on other cortical parameters. Computational models of self-organization and associative memory function in cortical structures such as the hippocampus, piriform cortex and neocortex provide a theoretical framework in which the role of these neuromodulatory effects can be analyzed. Neuromodulators such as acetylcholine and norepinephrine appear to enhance the influence of synapses from afferent fibers arising outside the cortex relative to the synapses of intrinsic and association fibers arising from other cortical pyramidal cells. This provides a continuum between a predominant influence of external stimulation to a predominant influence of internal recall (extrinsic vs. intrinsic). Modulatory influence along this continuum may underlie effects described in terms of learning and memory, signal to noise ratio, and attention.

Acetylcholine↗

PubMed2006

"Pusher syndrome" following cortical lesions that spare the thalamus.

Stroke patients with "pusher syndrome" show severe misperception of their own upright body orientation although visual-vestibular processing is almost intact. This dissociation argues for a second graviceptive system in humans for the perception of body orientation. Recent studies revealed that the posterior thalamus is an important part of this system. The present investigation aimed to study the cortical representation of this system beyond the thalamus. We evaluated 45 acute patients with and without contraversive pushing following left-or right-sided cortical lesions sparing the thalamus. In both hemispheres, the simple lesion overlap associated with contraversive pushing typically centered on the insular cortex and parts of the postcentral gyrus. The comparison between pusher patients and controls who were matched with respect to age, lesion size, and the frequency of spatial neglect, aphasia and visual field defects revealed only very small regions that were specific for the pusher patients with cortical damage sparing the thalamus. Obviously, the cortical structures representing our control of upright body orientation are in close anatomical proximity to those areas that induce aphasia in the left hemisphere and spatial neglect in the right hemisphere when lesioned. We conclude that in addition to the subcortical area previously identified in the posterior thalamus, parts of the insula and postcentral gyrus appear to contribute at cortical level to the processing of the afferent signals mediating the graviceptive information about upright body orientation.

Aged↗

PubMed2006

Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways.

UNLABELLED: NeuropeptideY-, Y2 receptor (Y2)-, and leptin-deficient mice show similar anabolic action in cancellous bone but have not been assessed in cortical bone. Cortical bone mass is elevated in Y2(-/-) mice through greater osteoblast activity. In contrast, leptin deficiency results in reduced bone mass. We show opposing central regulation of cortical bone. INTRODUCTION: Treatment of osteoporosis is confounded by a lack of agents capable of stimulating the formation of bone by osteoblasts. Recently, the brain has been identified as a potent anabolic regulator of bone formation. Hypothalamic leptin or Y2 receptor signaling are known to regulate osteoblast activity in cancellous bone. However, assessment of these pathways in the structural cortical bone is critical to understanding their role in skeletal health and their potential clinical relevance to osteoporosis and its treatment. MATERIALS AND METHODS: Long bones of 16-week male ob/ob and germline and hypothalamic Y2(-/-) mice were assessed by QCT. Cortical osteoblast activity was assessed histologically. RESULTS: The femora of skeletally mature Y2(-/-) mice and of leptin-deficient ob/ob and Y2(-/-)ob/ob mice were assessed for changes in cortical osteoblast activity and bone mass. Ablation of Y2 receptors increased osteoblast activity on both endosteal and periosteal surfaces, independent of leptin, resulting in increased cortical bone mass and density in Y2(-/-) mice along the entire femur. Importantly, these changes were evident after deletion of hypothalamic Y2 receptors in adult mice, with a 5-fold elevation in periosteal bone formation. This is in marked contrast to leptin-deficient models that displayed reduced cortical mass and density. These changes were associated with substantial differences in calculated strength between the Y2(-/-) and leptin-deficient mice. CONCLUSIONS: These results indicate that the Y2-mediated anabolic pathway stimulates cortical and cancellous bone formation, whereas the leptin-mediated pathway has opposing effects in cortical and cancellous bone, diminishing the production of cortical bone. The findings from conditional hypothalamic Y2 knockout show a novel, inducible control mechanism for cortical bone formation and a potential new pathway for anabolic treatment of osteoporosis.

Animals↗

PubMed2007

Exercise when young provides lifelong benefits to bone structure and strength.

UNLABELLED: Short-term exercise in growing rodents provided lifelong benefits to bone structure, strength, and fatigue resistance. Consequently, exercise when young may reduce the risk for fractures later in life, and the old exercise adage of "use it or lose it" may not be entirely applicable to the skeleton. INTRODUCTION: The growing skeleton is most responsive to exercise, but low-trauma fractures predominantly occur in adults. This disparity has raised the question of whether exercised-induced skeletal changes during growth persist into adulthood where they may have antifracture benefits. This study investigated whether brief exercise during growth results in lifelong changes in bone quantity, structure, quality, and mechanical properties. MATERIALS AND METHODS: Right forearms of 5-week-old Sprague-Dawley rats were exercised 3 days/week for 7 weeks using the forearm axial compression loading model. Left forearms were internal controls and not exercised. Bone quantity (mineral content and areal density) and structure (cortical area and minimum second moment of area [I(MIN)]) were assessed before and after exercise and during detraining (restriction to home cage activity). Ulnas were removed after 92 weeks of detraining (at 2 years of age) and assessed for bone quality (mineralization) and mechanical properties (ultimate force and fatigue life). RESULTS: Exercise induced consistent bone quantity and structural adaptation. The largest effect was on I(MIN), which was 25.4% (95% CI, 15.6-35.3%) greater in exercised ulnas compared with nonexercised ulnas. Bone quantity differences did not persist with detraining, whereas all of the absolute difference in bone structure between exercised and nonexercised ulnas was maintained. After detraining, exercised ulnas had 23.7% (95% CI, 13.0-34.3%) greater ultimate force, indicating enhanced bone strength. However, exercised ulnas also had lower postyield displacement (-26.4%; 95% CI, -43.6% to -9.1%), indicating increased brittleness. This resulted from greater mineralization (0.56%; 95% CI, 0.12-1.00%), but did not influence fatigue life, which was 10-fold greater in exercised ulnas. CONCLUSIONS: These data indicate that exercise when young can have lifelong benefits on bone structure and strength, and potentially, fracture risk. They suggest that the old exercise adage of "use it or lose it" may not be entirely applicable to the skeleton and that individuals undergoing skeletal growth should be encouraged to perform impact exercise.

Animals↗

PubMed1984

Events governing organization of postmigratory neurons: studies on brain development in normal and reeler mice.

The purpose of the present work is to examine some of the mechanisms responsible for the early architectonic differentiation of the central nervous system, as well as for the abnormal development which occurs in certain hereditary malformations. In order to approach these questions, the embryonic development of the cerebral cortex, the cerebellum, the inferior olivary complex and the facial nerve nucleus has been studied in normal and reeler mutant mice, using morphological methods. The adult reeler phenotype is characterized not only by extreme laminar abnormalities of cell positioning in the telencephalic and cerebellar cortices, but also by relatively less extreme, though distinct abnormal architectonics in non-cortical structures such as the inferior olive and the facial nerve nucleus. Study of the embryonic development of these structures reveals that neurons are generated at the normal time and migrate along normal pathways. Moreover, the processes of directional axonal growth, differentiation of class specific features of neurons and glia, and synaptogenesis appear similar in both genotypes and are probably not directly affected by the reeler mutation. However, in all instances, the early architectonic organization achieved by reeler cortical, Purkinje, olivary or facial neurons at the end of their migration is consistently less regular than in normal embryos. In addition, these anomalies become amplified during the later developmental period. This evidence for the early appearance of abnormalities in reeler embryos indicates that the disposition of neurons at maturity cannot be exclusively regarded as secondary to the maturation of cells, neurites and connections, but is contingent upon a specific mechanism. One may infer that the presence of a normal allele at the reeler locus is necessary for the normal completion of this histogenetic step, which consequently is submitted to genetic control. Although the factor(s) responsible for the stable configuration of the early architectonics is unknown, various hypotheses are considered. Several lines of evidence are presented which argue against a major role being played by diffusible factors, mesodermal components and afferent fiber systems. Two mechanisms are considered particularly worth evaluating: (1) a diminution of relative adhesivity between neurons and radial glial fibers at the end of migration, and (2) a stabilization of neuronal configuration by selective recognition-adhesion among postmigratory neurons. The reeler gene could, directly or indirectly, affect these cell-cell interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2000

Neuroimaging of chronic pain: phantom limb and musculoskeletal pain.

New developments in brain imaging lead to a better understanding of cortical and subcortical processes involved in pain perception and the establishment of chronic pain. For different forms of chronic pain long-term changes in cortical structures have been described. In patients with phantom limb pain and back pain alterations in the somatotopic organization of the primary somatosensory (SI) could be observed. The amount of this reorganization is correlated with the subjective pain rating. These changes, which are based on processes of neuronal plasticity, can partially be reversed by analgesic interventions. For the investigation of cortical processes concerning reorganization, EEG and MEG methods are most suitable because of their high temporal and spatial resolution. In conclusion, these findings open a new way for therapeutic interventions to prevent the development of chronic pain.

Back Pain↗

PubMed1996

In vivo regional cerebral blood volume: quantitative assessment with 3D T1-weighted pre- and postcontrast MR imaging.

PURPOSE: To assess the use of pre-and postcontrast three-dimensional (3D) T1-weighted images to obtain quantitative regional cerebral blood volume (rCBV) maps and to delineate the vascular system of the brain. MATERIALS AND METHODS: Sagittal 3D pre-and postcontrast T1-weighted images were acquired in 10 patients and two volunteers. The images were processed with a knowledge-based segmentation algorithm to obtain independent blood volume maps of gray matter (GM), white matter (WM), and blood vessels and to quantitate rCBV in various cortical and deep cortical structures. Localized maximum intensity projection (MIP)-rCBV images were used to reveal the brain's venous system and vascularity in and around any lesions present. RESULTS: Group-averaged (n = 8) rCBV maps from both GM (4.80% +/- 0.37) and WM (2.02% +/- 0.14) yielded a ratio of GM-to-WM rCBV of 2.38 +/- 0.20. The ratio of rCBV between cortical and deep cortical GM was 1.15. rCBV maps showed better vascular contrast than did the postcontrast images in delineation of blood vessels and in the lesions present in two patients. A localized MIP-rCBV image had more than five times higher vascular contrast-to-noise ratio than that of the postcontrast MIP image. CONCLUSION: rCBV maps can be obtained in a standard clinical setting and can be used to reveal information on local blood volume.

Adult↗

PubMed1985

Cytoskeletal reorganization and plasma membrane fusion in conjugating Tetrahymena.

The conjugation junction of Tetrahymena is the specialized site where plasma membrane fusion occurs between two cells of complementary mating types. The junction is constructed through a series of cooperative interactions and morphogenetic steps. A contact-mediated interaction between free-swimming, sexually mature and mating-competent cells of two complementary mating types induces a morphological transformation of the anterior tips. Cells then join in pairs aligned by the apposition of their modified tips. Thin sections show that the plasma membranes of the tips are separated by approximately 500 A of extracellular space, in which some strands of matrix material can be identified. The cytoplasmic face of the membrane is in contact with a junction-specific thick layer of electron-dense material. At hundreds of independent sites in this junction plasma membranes fuse in a limited manner, thereby establishing hundreds of separate membrane-ensheathed cytoplasmic channels that connect the two cells. At the same locations the thick submembrane layer is interrupted. Consequently, the junction appears to be a structure that is perforated with hundreds of pores. This study poses the question of whether the junction's submembrane layer is, or includes, a skeletal element. Cells were extracted with the non-ionic detergent Triton X-100 under conditions that yield cytoskeletal frameworks (CFs) that maintain the morphological integrity of the cells. The CFs include chromatin and also cortical structures such as microtubule bands, basal bodies, ciliary axonemes, kinetodesmal fibres and fibrillar epiplasm. CFs of conjugant pairs are also paired, indicating that the junction contains a skeletal element that is responsible for integrating the individual CFs into a higher-order complex. At the ultrastructural level the skeletal structure of the junction includes membrane lamina and a submembrane scaffold, residues of the plasma membrane and thick submembrane layer, respectively, both of which are interrupted at the pores. However, the two separate scaffolds are joined at the rims of the pores. This provides a means by which the separate CFs become integrated. On the basis of images of junctional CFs, which show interruptions of the scaffold without concomitant membrane fusion, but where laminae are pressed close together, a specific model of membrane fusion is proposed. According to this model, the submembrane skeletal scaffold regulates membrane fusion by limiting its occurrence, and the extent of its occurrence.

Animals↗

PubMed1993

Cytoplasmic segregation and cytoskeletal organization in the electric catfish giant electromotoneuron with special reference to the axon hillock region.

The cytoplasm of the highly polarized nerve cell is permanently segregated into domains with differing organellar composition. The mechanisms maintaining this segregation are largely unknown. In order to elucidate the potential role of cytoskeletal elements in this process we compared the cytoplasmic segregation within the giant electromotoneuron of the electric catfish (Malapterurus electricus) with the distribution of binding sites for antibodies against elements of the cytoskeleton. Most prominent cytoplasmic segregations include the formation of a subplasmalemmal cortical structure free of Nissl bodies and Golgi cisternae, the separation within the soma of domains containing rough endoplasmic reticulum and filament-rich domains, and the soma-axon transition. The cytoplasmic transition at the axon hillock forms a distinct borderline where Nissl bodies, Golgi cisternae and the bulk of lysosomes abruptly terminate and are excluded from the axoplasm. Synaptic vesicles and mitochondria are free to pass compartmental borders. Tropomyosin, spectrin, and alpha-actinin reveal a rather homogeneous immunofluorescence throughout the neuron. In contrast, neurofilament protein and tubulin display a distinctly increased immunofluorescence in the subplasmalemmal cortical layer, in dendrites as well as in the axon. The increase in immunofluorescence at the axon hillock exactly depicts the small transition zone from the somatic cytoplasm rich in Nissl bodies, Golgi cisternae and lysosomes to the differently structured axoplasm. The picture is similar for beta-tubulin, tyrosinylated and detyrosinylated alpha-tubulin. Detyrosinylated tubulin (glu-tubulin, which is contained in microtubules of increased stability) shows the most prominent enrichment in the axon. The distribution of myosin is comparable to that of neurofilament protein but there is less difference in immunofluorescence between the domains. Our results would be compatible with a role of microtubules together with (the closely associated) neurofilaments in the segregation of neuronal cytoplasmic domains. Active transport as well as stable binding to the somatic cytoskeleton might counteract a homogeneous cytoplasmic distribution of the various classes of organelles by diffusion.

Actinin↗

PubMedDate not supplied

[An electrophysiological analysis of the process of a shift in a dominant].

Correlation of electrical activity of the sensorimotor (representation of the forelimb and blinking and visual areas of rabbit cerebral cortex and VPL of the thalamus was studied by the method of spectral analysis during creation of the motor defensive dominant (by serial electrical stimulation of the forelimb) at the background of the blinking dominant. In the structures which realize the defensive reflex (sensorimotor cortex and VPL of the thalamus) a typical for the dominant state increase in the spectral power was observed in the delta range. This electrophysiological phenomenon was not accompanied by behavioural manifestations of the dominant. Formation of the latent defensive dominant destroyed the typical for the dominant state organization of biopotentials in the cortical structures responsible for realization of the blinking reflex. It seems likely that the blinking dominant in the process of its change for the defensive one inhibits behavioural manifestations of the new dominant focus.

Animals↗

PubMed1983

[Features of the structural organization of the sensomotor cortex during natural development and among the progeny of alcoholic animals].

Rats of both sexes were given alcohol for four months (15% alcohol in the first month, and 25% alcohol later on). The 21- and 30-day-old rats born to these parents displayed, in addition to the inhibited maturation of the sensomotor cortex, dystrophic alterations in neurons and their dendrites, which were more pronounced in the 21-day-old animals. Despite the signs of a reparative character, the cortical structural organization remained impaired as long as one month after birth. This indicates that alcohol intoxication interferes with postnatal development of the brain in their offspring.

Animals↗

PubMed2005

Development of the subchondral bone layer of the medial coronoid process of the canine ulna.

The medial coronoid process (MCP) of the ulna takes part in the weight-bearing function of the elbow in quadrupedal animals. In this study, the timing of development of a solid subchondral bone layer (SBL) of the MCP in the dog is investigated, as this might be important in the pathogenesis of the fractured medial coronoid process, a common disease in young dogs of larger breeds. The SBL is considered to make an important contribution to the strength of the MCP. In this study, the SBL is visualized at the humeral articular side (H-side) and in the radial notch (RN) via three-dimensional reconstructions of micro-CT scans (34 mum voxel size) in nine young golden retrievers. After micro-CT scanning, the area was investigated histologically. Gradually, the appearance of the SBL on the H-side changes from a trabecular aspect to an even surface with gaps and finally to a completely even surface. The surface in the RN is still rough at 24 weeks after birth, although some consolidation has occurred. Initially, the enchondral ossification activity, as observed in the histological sections, is high, but later, when the intertrabecular spaces are filled in with calcified cartilage and bone, activity is less evident. Some vessels penetrated the SBL, but it is unclear if they account for all the gaps in the surface seen in micro-CT. In addition, the formation of a cortical structure of the proximal ulnar shaft could be visualized. The bony cortex is already even at the mediocaudal side of the proximal ulna 4 weeks after birth, but remains trabecular at the dorsal side until 6 weeks later. We hypothesize that the observed differences in the formation of an even SBL or cortex can be explained by mechanical factors. A smooth cortical layer has an even thickness and will be stronger than a cortex with varying thickness. In the MCP, compressive forces exerted by the humerus may be responsible for the early smoothening on the H-side. In the proximal ulna, the resistance to bending in the sagittal plane will depend mainly on the caudal surface of the ulna (and dorsal surface of the radius), surfaces furthest away from the neutral axis. At least the caudal ulna smoothened first, thus providing stiffness against bending at an early age.

Animals↗

PubMed2000

Electrophysiological studies of myoclonus.

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification and about its generator mechanisms. The EEG-EMG polygraph provides the most essential information about the myoclonus of interest. Jerk-locked back averaging and evoked potential studies combined with recording of the long latency, long loop reflexes are useful to further investigate the pathophysiology of myoclonus, especially that of cortical myoclonus. A recent advance in magnetoencephalographic techniques has contributed significantly to the elucidation of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in each individual patient is important for selecting the most appropriate treatment of choice.

Electroencephalography↗

PubMed1984

Demyelinating polyneuropathy associated with monoclonal IgM-paraproteinaemia. Histological, ultrastructural and immunocytochemical studies.

Histological, ultrastructural and immunocytochemical findings of sural nerve biopsies from 2 patients with monoclonal IgM-paraproteinaemia are presented. In both cases the pathological IgM antibodies reacted with a myelin antigen which was identified as myelin-associated glycoprotein (MAG) by immunoelectroblot . Histology and electron microscopy showed typical features of a chronic demyelinating neuropathy with accompanying axonal degeneration. Immunohistochemical studies demonstrated IgM in the vicinity of endoneurial vessels and on some of the myelinated fibres. The localisation of IgM on the myelin sheath showed a typical pattern, which was similar to that found in binding studies with the patients sera on control nerves. It resembled the characteristic immunocytochemical staining pattern of MAG. Binding studies with the patients' sera on human and canine CNS material exhibited a clear labelling of white matter and certain, as yet unidentified structures within the cerebral and cerebellar cortex. In mixed glial cell cultures, the sera of both patients bound specifically to oligodendrocytes. Our observations are interpreted as immunohistochemical evidence that the anti-MAG antibodies of the patients' sera had bound to their antigenic target in the peripheral nerves. Because the antibodies clearly react to central myelin, oligodendrocytes and other not yet identified cortical structures, CNS involvement in such disorders should be considered.

Aged↗

PubMed2005

Pallial expression of Enc1 RNA in postnatal mouse telencephalon.

We analysed the pallial expression pattern of Enc1 (a member of the kelch family of genes) in postnatal mice (P1-P10). At early developmental stages this gene plays a role in the histogenesis of cortical structures [M.C. Hernández, P.J. Andrés-Barquin, S. Martínez, A. Bulfone, J.L.R. Rubenstein, M.A. Israel, Enc1: novel mammalian kelch-related gene specifically expressed in the nervous system encodes an actino-binding protein, J. Neurosci. 17 (1997) 3038-3051]. A restricted expression of Enc1 was found in the mouse pallium, notably within claustroamygdaloid derivatives of the lateral pallium and in some cortical layers in the lateral, dorsal and medial pallium sectors, with distinct regional differences. The strongest cortical expression was found in isocortical layer II and in the piriform cortex, anterior olfactory area and olfactory bulb mitral cells. The lowest signal occurred in the retrosplenial cortex. The subgranular layers V/VI were also positive, particularly layer V, with clearcut areal differences. The hippocampal CA3/CA4 areas and the dentate gyrus were strongly positive. The dorsolateral (core) portion of the claustrum and dorsal endopiriform nucleus were moderately positive, as were the amygdaloid lateral and basolateral nuclei.

Age Factors↗

PubMed2005

Reelin promoter hypermethylation in schizophrenia.

Reelin mRNA and protein levels are reduced by approximately 50% in various cortical structures of postmortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. In addition, the mRNA encoding the methylating enzyme, DNA methyltransferase 1, is up-regulated in the same neurons that coexpress reelin and glutamic acid decarboxylase 67. We have analyzed the extent and pattern of methylation within the CpG island of the reelin promoter in genomic DNA isolated from cortices of schizophrenia patients and nonpsychiatric subjects. Ten (The Stanley Foundation Neuropathology Consortium) and five (Harvard Brain Collection) schizophrenia patients and an equal number of nonpsychiatric subjects were selected from each brain collection. Genomic DNA was isolated, amplified (from base pair -527 to base pair +322) after bisulphite treatment, and sequenced. The results show that within the promoter region there were interesting regional variations. There was increased methylation at positions -134 and 139, which is particularly important for regulation, because this portion of the promoter is functionally competent based on transient transfection assays. This promoter region binds a protein present in neuronal precursor nuclear extracts that express very low levels of reelin mRNA; i.e., an oligonucleotide corresponding to this region and that contains methylated cytosines binds more tightly to extracts from nonexpressing cells than the nonmethylated counterpart. Collectively, the data show that this promoter region has positive and negative properties and that the function of this complex cis element relates to its methylation status.

Binding, Competitive↗