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16 recordsLinked to original sources

PubMed1976

A pilot study of cell production by the ganglionic eminences of the developing mouse brain.

Cell production in the medial and lateral ganglionic eminences in pre- and post-natal mouse brains was studied by recording the number, location and plane of cleavage of mitotic figures. The site of maximum cell production shifted progressively from the ependymal layer to an adjacent sub-ependymal proliferative compartment. In the latter, mitosis occurred without the nuclei participating in the migratory movement to the ventricular surface which is characteristic of the nuclei of the ependymal compartment. The sub-ependymal compartment persisted vestigially into post-natal life as the well known sub-ependymal layer.

Animals↗

PubMed1992

Transient calbindin-D28k-positive systems in the telencephalon: ganglionic eminence, developing striatum and cerebral cortex.

Calbindin-D28k (calbindin) is a member of the superfamily of calcium-binding proteins implicated in the regulation of intracellular calcium. In the mature brain, calbindin is widely expressed in neurons of the forebrain and the hindbrain, and in the telencephalon calbindin-like immunoreactivity is particularly strongly expressed by medium-sized neurons of the striatum and by certain other neurons in the cortex and subcortex. We have traced the development of calbindin expression in the forebrain of the rat, and report here that in addition to the steady development of these calbindin-positive neuronal systems, transient waves of calbindin expression occur in cells of the ventricular zones of the basal ganglia and cortex and in cells of the telencephalic regions derived from these ventricular zones including radial glia of the developing striatum. In the striatum and its ventricular zone (the ganglionic eminence, or GE) we identified four transient calbindin-positive systems in the perinatal period. First, calbindin-immunoreactive cells began to appear in the GE by embryonic day (E)18, and by E20 an extensive dorsal and lateral part of the GE was marked by dense calbindin-like immunoreactivity in the ventricular zone. This calbindin system peaked at postnatal day (P)0-P3 and disappeared by P15. Its presence suggests that the GE is divisible on a molecular basis into lateral and medial districts that may correspond to derivatives of the lateral and medial ventricular ridges. Second, a system of calbindin-positive processes appeared in the dorsal and lateral caudoputamen with temporal and spatial distributions matching the germinal zone system. Many of these processes could be traced from calbindin-positive cells in the ventricular zone of the GE, including processes stretching across the full width of the dorsal caudoputamen. Double-staining experiments demonstrated that these radial processes were Rat.401-positive, suggesting that they form a subset of radial glia in the developing telencephalon. These findings demonstrate that during development calbindin is expressed in glial as well as neural cells. They further suggest that the radial glia associated with the GE form heterogeneous populations, the transient calbindin-positive radial glia being associated with the lateral ridge of the GE and its derivatives. Third, a scattered population of calbindin-positive cells with morphologies different from the common medium-sized calbindin-immunoreactive neurons of the striatum appeared in the dorsal and lateral striatum from about E20 to P15. Some of these cells were close to the transient calbindin-positive radial processes in the same region, but others were not.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed2026

ARX mutation-associated interneuron defects provide insights into mechanisms underlying developmental epilepsies.

Cortical interneuron (cIN) dysfunction is associated with various neurodevelopmental and neurological disorders, including developmental epilepsies, autism spectrum disorders and intellectual disabilities. Mutations in ARX (aristaless-related homeobox) are linked to these conditions, with or without accompanying structural brain anomalies. We previously demonstrated that the loss of Arx in the mouse ganglionic eminence, the birthplace of cINs, is associated with seizures, whereas its loss in cortical excitatory neuron progenitor cells results in structural anomalies but no seizures. To elucidate the pathophysiological role of ARX in cINs and its relationship to seizure phenotype, Arx conditional mutant mouse lines were investigated using Gad2- and Nkx2.1-Cre drivers to target distinct populations in the cIN lineage. Our data demonstrate that ARX abrogation results in defects in cIN density and distribution, as well as perinatal lethality. In these mice, we observed defects in cell cycle exit, a biased loss of the marginal zone migration stream of cINs, shifts in cell fate from caudal ganglionic eminence to medial ganglionic eminence identity, and a reduced number of parvalbumin⁺ and somatostatin⁺ cINs, with parvalbumin⁺ cINs being more severely affected. Single-cell RNA sequencing combined with chromatin immunoprecipitation and sequencing revealed that ARX regulates key processes involved in cell cycle progression, cIN subtype differentiation and cIN migration. Investigation of one downregulated target gene, Lmo1, uncovered a potential mechanism by which ARX regulates the number and distribution of cINs in the cortex. Cortical slice cultures demonstrate that LMO1 inhibits cIN migration by repressing Cxcr4 expression, which encodes a key receptor involved in cortical guidance. These data indicate that ARX positively regulates cIN migration by derepressing LMO1's repressive role. Consistent with our mouse model, we observed a significant loss of parvalbumin+ and somatostatin+ cINs in the brain of a patient carrying a pathogenic variant of ARX, who was diagnosed with developmental epileptic encephalopathy. Together, our data provide novel insights into how ARX and its target genes regulate cIN development and migration and into the pathogenic mechanisms underlying a spectrum of neurodevelopmental disorders linked to loss of ARX.

Animals↗

PubMed1991

Cells from embryonic rat striatum cocultured with mesencephalic glia express dopaminergic phenotypes.

To study region-specific transmitter phenotype expression, cells of embryonic day 14 (E14) rat neostriatum (ganglionic eminence plus cortical plate) or of the substantia nigra (ventral mesencephalon) were cultured on glial cells either from substantia nigra or neostriatum (E21). By antityrosine hydroxylase immunocytochemistry, immunoblotting of tyrosine hydroxylase protein and quantitation of dopamine and its metabolites by HPLC, dopaminergic cells were revealed in nigral and neostriatal cultures plated on nigral glial cells. No dopaminergic cells were found among neostriatal neurons plated on neostriatal glial cells. It is concluded that glia from substantia nigra but not glia from neostriatum is capable of inducing development or promoting survival of dopaminergic cells.

Animals↗

PubMed1991

Early development of the human thalamus: Golgi and Nissl study.

Qualitative and quantitative parameters of the early neuronal development of the thalamus were examined in human embryos and fetuses ranging in age from 5-16 gestational weeks (g.w.) using Nissl stained and Golgi impregnated tissue. In the earliest period analyzed, from 5-6 weeks of gestation, dorsal and ventral parts of the human thalamus were poorly differentiated structures forming the sides of the third ventricle. At 6 g.w., the prospective thalamic anlage consisted of the ventricular (VZ), the intermediate (IZ) and the marginal zones (MZ). The neurons in the VZ were bipolar and radially arranged to the ventricular surface. From 6-8 gestational weeks detached bipolar or branched bipolar cells with horizontal or oblique orientation were encountered in the IZ and occasionally in the MZ. In the period between 10-14 weeks of gestation, segregation of neurons into different thalamic nuclei began. The lateral geniculate nucleus, centrum medianum and mediodorsal nucleus were the first to be distinguished. In comparison with the previous period, the neurons throughout the rostro-caudal axis of the thalamus were more differentiated, with a higher number of primary dendrites that were often bifurcated. This resulted in various shapes of immature neurons: simple uni- and bipolar (type 1), branched uni- and bipolar (type 2) and young multipolar (type 3). In addition, the first spines were frequently observed on dendrites at 12 weeks of gestation. At 14-16 weeks of gestation, segregation of the neurons into thalamic nuclei continued. The neurons exhibited further dendritic differentiation that followed the caudo rostral gradient. For the first time, multipolar neurons, especially in the caudal part, could be subdivided into two classes: multipolar with a 'bushy' appearance, the result of many primary dendrites with several bifurcations and 'simpler' multipolar neurons with fewer and less branched primary dendrites. Neuronal differentiation was further expressed by an increase in the total dendritic length and somatic surface, up to six and three times, respectively, from the earliest period analyzed to 16 weeks of gestation. Dendritic length increased initially by the formation of new primary branches and their elongation and secondly by formation of higher branch orders. At 16 g.w., a group of immature cells were observed dorsally, on the frontal sections through the rostral thalamus. Its ganglionic eminence origin is discussed.

Analysis of Variance↗

PubMedDate not supplied

Emergence of connectivity in the embryonic rat parietal cortex.

In order to understand how cortical circuitry is put together, we examined the emergence of corticofugal projection cells and the arrival of subcortical afferents in the presumptive parietal cortex of the embryonic rat cerebrum. Afferent and efferent projections were selectively labeled by applications of the lipophilic tracers DiI and DiA in aldehyde-fixed brains of 12-18-d-old rat embryos (E12-E18; gestation: 21 d). On E12 and E13, the neocortical anlage consists of a ventricular zone and a preplate, with no extracortical connections. By E14, just prior to the appearance of the cortical plate, polymorphic cells located in the ventrolateral preplate of the telencephalic vesicle send out the first group of corticofugal axons toward the ganglionic eminence. Shortly thereafter, the cortical plate emerges as a dense band of radially oriented cells that also contribute to the corticofugal projection. By E15, axons of the early cortical projection cells cascade through the striatal primordium, the future site of the internal capsule. At the time of cortical plate formation and initial corticofugal axon outgrowth, ascending corticopetal axon systems have not yet arrived in the neocortex. Double-labeling experiments in which one dye is placed in the neocortex and the other in the ipsilateral dorsal thalamus reveal that cortical efferents encounter the first ascending wave of thalamofugal axons at the level of the striatum. Collectively, these two axonal systems bridge the necortex and the diencephalon. Upon their arrival in the neocortex on E16, thalamic axons follow a ventrolateral to dorsomedial course within the intermediate zone. Thalamic axons are the first subcortical afferent system to arrive in the neocortex. Other ascending afferent systems arising from the midbrain tegmentum enter the neocortex after E17. Comparison of thalamocortical and tegmentocortical projections in two halves of the same brain and across various embryonic ages clearly reveals that the two projection systems differ in their trajectories as well as in their time of arrival. Present observations challenge the view that the precocious arrival of subcortical axons provides the impetus for cortical maturation, and suggest that cortical plate differentiation and the initial organization of corticofugal projection patterns occur independent of ascending pathways.

Afferent Pathways↗

PubMed1979

Autoradiographic study of the development of the neostriatum in the rabbit.

Autoradiographic labelling has been employed to analyze the morphogenesis of the neostriatum. Pregnant rabbits received a single intraperitoneal injection of tritiated thymidine at different stages of gestation. Careful microscopical observation of the autoradiographs shows that cellular components of the neostriatum originate between days 15 and 18 of the intrauterine life from a layer of proliferating matrix cells that lies on the floor of the anterior part of the lateral ventrical (ganglionic eminence). From this proliferating layer, precursor cells migrate outwards to reach the developing neostriatum in a sequential fashion according to two gradients of histogenesis. Thus, it was found that neurons formed at early stages occupy a ventromedial position in the neostriatum, while those formed at later stages occupy a dorsolateral position (ventromedial to dorsolateral gradient). Furthermore, the present study indicates that the rostral regions of the neostriatum arise somewhat later than the caudal ones, demonstrating the existence of a caudocephalic gradient of cytogenesis.

Animals↗

PubMedDate not supplied

Dyke Award. The search for human telencephalic ventriculofugal arteries.

Our study traced the vascular development of the fetal telencephalon in the last two trimesters of gestation and the first 15 years of life in 60 fetal and childhood brains. We filled the macro- and microvascular beds with Microfil and made stereoscopic observations of cleared 0.5- to 1.0-cm-thick sections. Separately, we identified developing vascular structures histologically. In our youngest specimen (16-weeks gestation), transcerebral channels with walls consisting of a single layer of endothelium and varying in diameter from 10 to 50 microns originated from leptomeningeal arteries and veins at right angles to the surface and passed through the cortical plate (future cortex). They branched at varying depths within the mantle and germinal matrix surrounding the lateral ventricles. At deeper levels the channels freely anastomosed with each other. A cortical microvascular network did not appear until 22 to 24 weeks. The new endothelial channels were derived from leptomeningeal vessels and from larger transcerebral channels. Most regions of isocortex developed a microvascular plexus simultaneously, regardless of degree of maturation. Striatal channels matured earlier than extrastriatal channels, having developed a muscularis to within 100 microns of the ganglionic eminence by 22- to 24-weeks gestation. Maturation of the vascular walls of extrastriatal channels into proper arteries and veins occurred during the first postnatal year. Anastomotic channels were present throughout the leptomeningeal, striatal, and extrastriatal regions in all of our specimens from 16 weeks gestation to 15 years old. Our study does not support the existence of ventriculofugal arteries and deep white matter arterial border zones in the human fetus and neonate, which have been postulated to be the basis of "periventricular" leukomalacia.

Arteries↗

PubMed1979

[Neuropharmacological data on the striatum].

The striatum constitutes the most voluminous basal ganglia in man. It is issued from ganglionic eminences which are very early bound by limbic kernels. If the cortical and reticulo-spinal projections have been first described the existence of anatomical connexions with the limbic system offers a large number of functional possibilities. The knowledge of the distribution of the different chemical substances which are present within this structure as well as the enzymes necessary for their synthesis and destruction permits to establish a chemical mapping, the dopaminergic one being the best known. The dopaminergic synaptic function in the striatum helps to understand the respective roles of the pre and post-synaptic receptors as well as the mechanisms by which the other neuromediators can modulate the dopaminergic activity, the cyclic nucleotides being often necessary for this action. These fundamental data subtend the mechanism of action of most of the drugs which are involved in extrapyramidal phenomenons (neuroleptics, dopaminergic agonists) and allows to put forth physiopathological hypothesis on Parkinson disease, Huntington chorea, as well as certain induced or spontaneous dyskinetic states. The functions of the striatum are then evoked: if the role of this structure in motor control is critical, its involvement in complex behaviours is strongly suggested.

Animals↗

PubMed1977

The location of nuclei of different labelling intensities in autoradiographs of the anterior forebrain of postnatial mice injected with [3H]thymidine on the eleventh and twelfth days post-conception.

The location of neuron nuclei of different labelling intensities in autoradiographs of the anterior forebrain of two 22 day old mice which had been injected with [3H]thymidine at 11 and 12 days post-conception respectively was charted on photocollages of sections enlarges 175 times. The pattern of distribution of the heavily labelled nuclei, i.e. those nuclei belonging to cells most likely to have been born shortly after the time of [3H]thymidine injection, indicated that the inner two thirds of the neocortex is laid down along a ventro-dorsal gradient, i.e. the lateral neocortex starts to form before the dorsal; and that cells born at a particular time lie in cortical layer VI at the dorsal edge of the gradient is traced ventrally. Progressively more weakly labelled cells formed intermediate steps in this migration. A model or cortical growth fitting these findings is presented. Some inferences are also made about the possible role of the ganglionic eminences in providing cortical cells, at least during the initial stages of cortical histogenesis.

Animals↗

PubMed1975

Melatonin effects on brain. Interaction with microtubule protein, inhibition of fast axoplasmic flow and induction of crystaloid and tubular formations in the hypothalamus.

[3-H]Melatonin administered in vivo in the rat cisterna magna became associated with a vinblastine-precipitable protein. Melatonin treatment decreased microtubule protein content by 44% in the arcuate-median eminence region and by 19% in the remaining hypothalamic block, being without significant effect on the cerebral cortex. Superior cervical gangliectomy but not pinealectomy increased microtubule protein content of the rat hypothalamus. Norepinephrine brought about a significantly greater decrease in hypothalamic microtubule protein levels of ganglionectomized rats than in sham-operated or in ganglionectomized-pinealectomized animals. Melatonin treatment induced in most of the axons ending in the pericapillary zone of the rat median eminence crystaloid and tubular formations. Rapid axonal transport in retinal ganglion cells of rabbits was inhibited to the extent of 71.9 and 87.2% by previous exposure to 1.5 of 15 mu g of melatonin intravitreally; melatonin did not affect retinal protein synthesis in this experimental model. These results suggest that melatonin interacts significantly with microtubule or actin-like protein in brain.

Animals↗

PubMed1991

A comparative pathological study of three strains of Trypanosoma cruzi in an experimental model.

Trypanosoma cruzi, the etiological agent of Chagas' disease, shows a wide variation in its biological behaviour depending on the geographical distribution of different strains. Moreover, some strains can show variations with the course of time. We have studied the tissular tropism of three strains of T. cruzi, Cali, Bolivia and Y, from different geographical origins (Colombia, Bolivia and Brasil respectively) on Swiss mice in order to detect any possible modification in their behaviour attributable only to parasite but not to host variations. The anatomopathological study of sections from heart, brain, liver, spleen, lymphatic ganglion, skeletal muscle and colon from Swiss mice infected with these strains has evidenced the presence of some important discrepancies between the tissular tropism expected from their former descriptions, and classical typification and then observed lesions. The greatest variations were found in the Y strain which had been described as eminently reticulotropic but presented lesions in all the organs except the spleen and lymphatic ganglion. We consider that the variations found in our study can only be explained in terms of changes in the properties of the strains considered, and conclude that the classic typification techniques based on the constancy of the characteristics of the parasite are not fully reliable for the description and clinical management of some evolving strains.

Animals↗

PubMed1978

Hemodynamic effects of electrical stimulation of forebrain angiotensin and osmosensitive sites.

Previous studies from this laboratory have indicated an important role for angiotensin-sensitive anteroventral third ventricular (AV3V) brain structures in normal regulation of arterial pressure and development of renal hypertension. The present experiments examined the effects of electrical stimulation of these periventricular areas on arterial pressure and regional blood flow in the anesthetized rat. Electrodes were placed in the AV3V region 3-10 days prior to acute studies. Blood flow was measured in extracorporeal blood flow circuits. Electrical stimulation produced only small changes in arterial pressure. Despite the small pressure changes, stimulation caused marked frequency-dependent alterations in regional blood flow. Renal and splanchnic flows were reduced while hindlimb flow was increased. Resistance changes were abolished by surgical denervation or ganglionic blockade but were unaffected by adrenalectomy. Hemodynamic responses to AV3V stimulation were abolished by a lesion in the area of the median eminence. It may be concluded that AV3V stimulation, through activation of pathways descending through the ventromedial hypothalamus-median eminence region, produces profound regional blood flow shifts without greatly altering arterial pressure.

Adrenalectomy↗

PubMed1991

Immunocytochemical distribution of FMRFamide-like substance in the brain of the cloudy dogfish, Scyliorhinus torazame.

The distribution of the molluscan cardioexcitatory tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) in the brain of the cloudy dogfish, Scyliorhinus torazame, was examined by immunocytochemistry. FMRFamide-like immunoreactivity was demonstrated to occur extensively in various regions of the dogfish brain, except for the corpus cerebelli. Immunoreactive neuronal perikarya were located in the ganglion of the nervus terminalis, the preoptic area, and the hypothalamic periventricular gray matter consisting of the nucleus medius hypothalamicus, the nucleus lateralis tuberis, and the nucleus lobi lateralis. Some of the immunoreactive cells in the hypothalamus were identified as cerebrospinal fluid-contacting neurons. The bulk of the immunostained fibers in the nervus terminalis penetrated into the midventral portion of the telencephalon and ran dorsocaudally toward the basal telencephalon and hypothalamus, showing radial projections or ramifications. The labeled fibers were abundant in the midbasal part of the telencephalon and in the hypothalamus, where some fibers were found in loose networks around the cell bodies of the nucleus septi and hypothalamic periventricular nuclei. The fibers demonstrated in the hypothalamus terminated around the vascular wall of the primary capillary plexus of the median eminence or penetrated deeply into the pars intermedia of the hypophysis. These results suggest that, in the dogfish, an FMRFamide-like substance participates in the regulation of adenohypophysial function. This molecule may have a role as a neurotransmitter and/or neuromodulator in the central nervous system.

Amino Acid Sequence↗

PubMed1992

Short-day stimulation of testicular activity and immunoreactivity of the hypothalamic GnRH system in mink following deafferentation of the pineal body by bilateral superior cervical ganglionectomy and melatonin replacement.

The effects of superior cervical ganglionectomy on testicular function (testis volume and plasma testosterone levels) and the immunocytochemical activity of the GnRH hypothalamic system were studied in the mink, a short-day breeder. Animals reared in a natural photoperiod were (i) ganglionectomized at four different times during the period extending from the end of summer to the end of autumn (September 15, October 20, October 28, and December 1), and (ii) reared for 50 days in a short gonadostimulatory photoperiod (4L:20D). Lastly, an attempt was made to overcome the effects of superior cervical ganglion removal by administering melatonin to mink reared in a natural photoperiod. In mink reared in a natural photoperiod, deafferentation of the pineal on September 15 (L = 12.5 h) or October 20 (L = 10.5 h) resulted in consistently low values of testicular volume and plasma testosterone until the end of the experiment (February). When the operation was performed on October 28 (L = 10 h) testicular activity was initiated but only lasted a short time and did not allow maximal gonadal development. When superior cervical ganglionectomy was carried out on December 1 (L = 8.5 h), during the phase of renewed testicular activity, the increases in testicular volume and testosterone levels were not affected by the operation and the subsequent variation of these parameters was identical to that observed in intact animals. Similarly, in mink reared for 50 days in a photoperiod of 4L:20D before superior cervical ganglionectomy, deafferentation of the pineal did not prevent gonadostimulation induced by short days.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1992

Further study of the aberrant optic nerve projection to olfactory cortex.

When implanted into the cerebral hemisphere, the regenerating optic nerve of the adult frog (Rana pipiens) forms a well-defined terminal field in the pars ventralis of the lateral (olfactory) cortex, and sometimes expands medially into the postolfactory eminence. These adjacent areas receive their normal input from the main olfactory bulb. The aberrant projection extends caudally toward the core neuropil of the medial amygdaloid nucleus, which receives its normal input from the accessory olfactory bulb, but does not enter this vomeronasal sector of the amygdala. The present study tests whether: 1) optic fibers would innervate the vomeronasal amygdala after surgical ablation of the accessory olfactory bulb, 2) the projection would transpose into adjacent cortex after olfactory cortex lesions, and 3) the projection would overflow into adjacent areas after being amplified by hemisection at the di-telencephalic junction (to minimize escape of fibers into the diencephalon). The retinal projection always terminated in the olfactory cortex when this area was intact, or in spared fragments of it after radical cortical lesions, but never entered the vomeronasal amygdala in any specimen, as studied by autoradiographic and horseradish peroxidase tracing techniques. With forebrain hemisection, the cortical terminal field increased in thickness but remained confined to the olfactory area. However, the interruption of the lateral forebrain bundle induced a new projection to the striatum in a region neighboring but separate from the olfactory cortical field. These findings support the hypothesis that retinal fibers have a specific affinity for primary olfactory cortex that is not normally allowed expression in development. Retinal fibers may also have a latent affinity for the striatum that is unmasked after deafferentation.

Animals↗