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PubMed1978

Keratan sulfate-like glycosaminoglycan in the cerebral cortex of the brain and its variation with age.

A keratan sulfate-like substance was found kn the cerebral cortex proteoglycans of rats. This substance tripled during the rapid growth phase from 1 to 3 months of age and then decreased steadily to a negligible quantity in the senescent rat, aged 25 months. In contrast, the uronic acid-containing glycosaminoglycans remained constant during the life span studied. The marked decrease observed in the proportion of keratan sulfate-like moiety to the other glycosaminoglycans in the cerebral cortex of the senescent rat (aged 25 months) compared with the young adult rat (aged 3 months) may explain the reduced extracellular volume observed by others in the senescent brain.

Aging↗

PubMed1976

Guanylate cyclase. Subcellular distribution in cardiac muscle, skeletal muscle, cerebral cortex and liver.

1. Guanylate cyclase of every fraction studied showed an absolute requirement for Mn2+ ions for optimal activity; with Mg2+ or Ca2+ reaction was barely detectable. Triton X-100 stimulated the particulate enzyme much more than the supernatant enzyme and solubilized the particulate-enzyme activity. 2. Substantial amounts of guanylate cyclase were recovered with the washed particulate fractions of cardiac muscle (63-98%), skeletal muscle (77-93%), cerebral cortex (62-88%) and liver (60-75%) of various species. The supernatants of these tissues contained 7-38% of total activities. In frog heart, the bulk of guanylate cyclase was present in the supernatant fluid. 3. Plasma-membrane fractions contained 26, 21, 22 and 40% respectively of the total homogenate guanylate cyclase activities present in skeletal muscle (rabbit), cardiac muscle (guinea pig), liver (rat) and cerebral cortex (rat). In each case, the specific activity of this enzyme in plasma membranes showed a five- to ten-fold enrichment when compared with homogenate specific activity. 4. These results suggest that guanylate cyclase, like adenylate cyclase, and ouabain-sensitive Na+ + K+-dependent ATPase (adenosine triphosphatase), is associated with the surface membranes of cardiac muscle, skeletal muscle, liver and cerebral cortex; however, considerable activities are also present in the supernatant fractions of these tissues which contain very little adenylate cyclase or ouabain-sensitive Na+ + K+-dependent ATPase activities.

Adenylyl Cyclases↗

PubMed1979

Early ultrastructural changes in the cerebral cortex of rat during ischemia.

The conducted investigation of the cerebral cortex of the rat during different survival periods following reduction in the cerebral circulation demonstrated an early occurence of ischemic changes characterized by different states of nerve and glial cells. The largest group was made up of neurons of deeper layers exhibiting reactive state of the nucleus and nucleolus and signs of chromatolysis in the cytoplasm. A less common pathology was represented by "dark" type changes observed in small stellate and pyramidal neurons of superficial layers. Changes of glial units manifested mainly as swelling and partial melting. The changes observed in neurons are indicative of variability of neurons of superficial and deep layers in sensitivity as well as of different mechanisms underlying structural regulation of cell metabolism and ensuring its optimum level and organization for each functional state.

Animals↗

PubMed1979

Rehabilitation following early malnutrition in the rat: body weight, brain size, and cerebral cortex development.

Sprague-Dawley rats were malnourished by giving their mothers an 8% casein diet starting at day 10 of gestation, while controls were fed a 24% casein diet. Starting at postnatal day 20 (P20), rehabilitation of the malnourished animals was attempted by: (1) feeding both mother and young a 24% casein diet, (2) leaving the pups with their mothers until they were 40 days old, and (3) reducing the litter size from 8 to 4 pups. Observations were made on aldehyde-perfused tissue from animals 20, 40 and 70 days old. The somatosensory cortex from one hemisphere was embedded in Araldite, and that from the other side was processed fro Golgi staining. At 20 days of age the body weight of the malnourished animals was 21% that of the controls, but at 70 days it was no longer different. The anterior-posterior length, the width, and the height of the cerebral hemispheres were also significantly reduced at P20, but the differences had disappeared by P70. The thickness of area 3 of the cerebral cortex was measured in 1 micron sections. It was significantly reduced in the malnourished animals at P20, but at P40, following rehabilitation, the difference was no longer statistically significant. In tangential 1 micron sections the fraction of the volume of tissue occupied by neuropil was measured in layers II through IV. At P20 it was significantly reduced only in the upper half of layers II/III of the malnourished animals; at P40 this difference was no longer present. The mean volume of upper layer II/III cell bodies was estimated and found to be significantly reduced in the experimental animals at P20 but not at P40. In the Golgi preparations, pyramidal cells in upper layer II/III were studied. Their estimated volume, as well as the thickness of their basal dendrites, was significantly reduced in the 20 day malnourished animals, but not in the rehabilitated animals. These results show that animals severely malnourished until 20 days of age can reach normal body weight and attain cerebral hemispheres of normal size when proper nutrition is provided. The effects of malnutrition on the cerebral cortex of these animals are most apparent in upper layer II/III which, during the time of nutritional restriction, is the least developed of the cortical layers. However, when proper nutrition is provided, the cerebral cortex may attain normal morphology.

Animals↗

PubMed1975

Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex.

Electrophysiologically identified pyramidal tract neurons in the rat cerebral cortex were tested with norepinephrine, acetylcholine, adenosine 3',5'-monophosphate (cyclic AMP), and guanosine 3',5'-monophosphate (cyclic GMP) applied by microiontophoresis. The neurons were usually inhibited by norepinephrine and cyclic AMP, but excited by acetylcholine and cyclic GMP. These opposing responses of pyramidal tract neurons to cyclic AMP and cyclic GMP suggests that these two nucleotides could function as reciprocal intracellular second messengers for norepinephrine and acetylcholine, respectively.

Acetylcholine↗

PubMed1975

The involvement of lysophosphoglycerides in neurotransmitter release; the composition and turnover of phospholipids of synaptic vesicles of guinea-pig cerebral cortex and Torpedo electric organ and the effect of stimulation.

(1) Crude synaptosomal fractions (P2) derived from guinea-pig cerebral cortex were incubated in the presence of 50 mM KCl in a Krebs-glucose medium. Torpedo marmorata electric organs were stimulated electrically in vivo at 5 pulses/sec for 30 min by electrodes placed on the electric lobe. Synaptic vesicles were isolated from each source and the phospholipid compositions analysed and compared with vesicles from unstimulated controls. (2) Lysophosphatidylcholine was the only lysophosphoglyceride demonstrable in the synaptic vesicles from either source and its low levels did not increase as a result of chemical or electircal stimulation. In each case there was a close similarity of the phospholipid distributions in the vesicles taken from control and stimulated samples. (3) Control experiments indicated extensive decreases in the acetylcholine content of the vesicles from the stimulated electric organ and smaller decreases in the acetylcholine content of the synaptic vesicles from stimulated crude synaptosomal fractions. These fractions were found to respire linearly in the presence of 10 mM glucose and the vesicle fractions were shown to have low levels of contaiminating membranes as judged by marker enzyme analyses. (4) Crude synaptosomal fractions from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium with labelled fatty acids and [3H]glucose in the presence or absence of 50 mM KCl. Subsynaptosomal fractionation was carried out and specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomes) and H (disrupted synaptosomes). The release of neurotransmitter did not significantly enhance the labelling of phospholipids in any of the fractions studied as compared with phospholipids from unstimulated fractions. This was found after two incubation times and using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose.

Acetylcholine↗

PubMed1979

Temperature coefficients of affinity constants for the binding of antagonists to muscarinic receptors in the rat cerebral cortex.

1 The temperature coefficients of binding of a series of muscarinic antagonists to their receptors in membrane preparations from the rat cerebral cortex has been examined. 2 At 37 degrees C the affinity constants agree with those determined by antagonism of acetylcholine-induced contractions of the guinea-pig ileum. 3 The temperature-dependence of the affinity constants is low; for the antagonists examined, the affinity constants at 0 degrees C differ by less than a factor of 3 from those measured at 37 degrees C. 4 There are qualitative similarities between the estimates of the temperature coefficient of binding of the antagonists to receptors in ileum strips and in the cerebral cortex.

Animals↗

PubMed1979

Bidirectional movement of gamma-aminobutyric acid in cerebral cortex slices incubated in small volumes of medium.

Rat cerebral cortex slices were incubated in small volumes of medium in order to study the bidirectional movements of gamma-aminobutyric acid (GABA) between tissue and medium, and to measure the extent of release of endogenous amino acids of interest as potential neurotransmitters. The apparent uptake, real uptake, and net change of GABA were calculated from the changes in [14C]GABA and endogenous GABA in the medium. The extent of release of endogenous amino acids was dependent upon the amino acid the duration of incubation, and the volume of incubating medium. Substantial amounts of endogenous amino acids may accumulate in the medium under conditions commonly employed in amino acid uptake studies. The accumulation of endogenous GABA may affect the calculation of GABA uptake when this is based on the initial specific activity of exogenous [14C]GABA. The difference between apparent uptake and real uptake was particularly prominent in the presence of the depolarizing agents, potassium or veratridine, which caused a marked increase in GABA release. Exchange or net release of GABA was found when slices were incubated briefly in media containing 1.3 micrometer or 12.5 micrometer exogenous GABA; net uptake accounted for 50% of observed uptake when slices were incubated in media containing 25 micrometer GABA.

Amino Acids↗

PubMed1975

[Energy state of the cerebral cortex of the cat during hyperventilation (author's transl)].

Average Po2 and Pco2, local blood flow and pH values in the cerebral cortex of the cat were measured during passive hyperventilation (arterial Pco2 below 19 mm Hg). At defined intervals tissue samples were taken for metabolite analysis. The object of the study was to correlate the data obtained on the brain surface with metabolic responses. Immediately after the start of hyperventilation blood flow decreased, average cortical tissue pressures of O2 and CO2 fell, and there was a simultaneous rise in cortical pH. At a later stage in the experiment the local blood supply reverted to its resting level. Despite a fivefold rise in tissue lactate level during hyperventilation and a decrease in local O2 pressure on the brain surface to 5-10 mm Hg the degree of phosphorylation of energy rich phosphates was not less than under normal conditions of oxygenation. Our investigations showed no evidence of energy lack in cerebral cortex cells during hyperventilation. Cellular hypoxia and its characteristics are defined. The possible causes of raised tissue lactate levels during hyperventilation despite the lack of evidence of cellular hypoxia are discussed.

Adenosine Diphosphate↗

PubMed1978

Idiopathic Parkinsonism with Lewy-type inclusions in cerebral cortex. A case report.

A case of idiopathic parkinsonism showed specific neuropathological findings, namely, the diffuse appearances of intracytoplasmic inclusions of Lewy type in the cerebral cortex in addition to many Lewy bodies in the pigmented brain stem nuclei. The staining properties and the ultrastructure of the inclusions in the cerebral cortex had a strong resemblance to those of the Lewy bodies in the substantia nigra, though a few electron microscopical differences were observed. Almost all of these 'cortical inclusions' were homogeneous or had an obscure core in their center, and they gave the impression of immature Lewy bodies.

Adult↗

PubMed1977

Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat.

Projections are described from the basolateral, lateral and anterior cortical nuclei of the amygdaloid complex, and from the prepiriform cortex, to several discrete areas of the cerebral cortex in the rat and cat and to the mediodorsal thalamic nucleus in the rat. These projections are very well-defined in their origin, and in their area of laminar pattern of termination. The basolateral amygdaloid nucleus can be divided into anterior and posterior divisions, based on cytoarchitectonic and connectional distinctions. In both the rat and cat the posterior division projects to the prelimbic area (area 32) and the infralimbic area (area 25) on the medical surface of the hemisphere. The anterior division projects more lightly to these areas, but also sends fibers to the dorsal and posterior agranular insular areas and the perirhinal area on the lateral surface. Furthermore, in the cat the perirhinal area is divided into two areas (areas 35 and 36) and the anterior division projects to both of these and also to a ventral part of the granular insular area; this last area is adjacent to, but separate from the auditory insular area and the second cortical taste area. In most of these areas, the fibers from the basolateral nucleus terminate predominantly in two bands: one in the deep part of layer I and layer II, and a heavier band in layer V (in the rat) or layers V and VI (in the cat). The lateral amygdaloid nucleus projects heavily to the perirhinal area, and also to the posterior agranular insular area. These fibers terminate predominantly in the middle layers of the cortex, although the cellular lamination in these two areas is relatively indistinct. The anterior cortical amygdaloid nucleus and the prepiriform cortex both project to the infralimbic area and the ventral agranular insular area, and the anterior cortical nucleus also projects to the posterior agranular area and the perirhinal area. In all of these areas, the fibers from these olfactory-related structures terminate in the middle of layer I. In the rat, the two divisions of the basolateral nucleus also project to the medial segment of the mediodorsal thalamic nucleus, with the anterior division projecting mainly to the posterior part of this segment and the posterior division to the anterior part. The endopiriform nucleus, deep to the prepiriform cortex, projects to the central segment of the mediodorsal nucleus; this may constitute the major olfactory input into the mediodorsal nucleus, since little or no projection could be demonstrated from the prepiriform cortex itself. Projections to the mediodorsal nucleus have not been found in the cat.

Afferent Pathways↗

PubMed1979

Sets of neurons in somatic cerebral cortex of the cat and their ontogeny.

The process of set formation is briefly reviewed and five monothetic schemes for classification of neurons in the somatic cerebral cortex are described. Criteria for evaluation of neuronal sets are presented and applied to the five different monothetic classification schemes. Classification by size and distribution of peripheral receptive fields orders existing data on cortical neurons better than classification by possession of an axon in the pyramidal tract, by modality, by lability of receptive field, or by 'lemniscal properties'; however, no monothetic scheme orders all the data. A useful polythetic scheme, using s and m terminology is suggested. The ontogeny of the cerebral cortex is reviewed in detail. It is suggested that sa neurons are Golgi type II neurons while m neurons are Golgi type I neurons. The hypothesis is presented that wide-field or m neurons develop and are recognizable before small-field or sa neurons in ontogeny. Evidence regarding this hypothesis is indirect, often conflicting, but suggestive that the hypothesis may be correct. The idea that m neurons may also be phylogenetically older than sa neurons is presented and shown to be consistent with ontogenetic data and interpretations.

Animals↗

PubMed1979

[Cerebral cortex biopotential and blood oxygenation in glaucomatous patient (author's transl)].

This report presents the data of blood oxygenation investigations (performed according to the method of oxyphemography) of cerebral cortex biopotential determination (EEG) in 32 glaucomatous patients (27 having a bilateral process in developed and advanced stages of the disease. The majority of the patients appeared to have oxygen deficiency (26 subj.) and anomalous EEG (29 subj.). A statistically rather high coefficient of correlation between changes in EEG and OHG deviations was determined. The results enabled the authors to conclude that low cerebral cortex activity in glaucoma patients might be the result of blood oxygen deficiency.

Adult↗

PubMed1978

Quantitative studies in the cerebral cortex of aging humans.

The capillary network of the human cerebral cortex was morphometrically investigated in a young, aged and aged hypertonic group. In the aging cortex, augmented values of capillary diameter and volume are accompanied by smaller distances between capillaries and an extended length per unit cortex volume. An increased capillary diameter of the aged hypertonic group is probably due to a high blood pressure. The regulating influence of the surrounding astroglia and the extracellular fluid on capillaries seems to lack. In comparison to normotonic brains, higher distances between capillaries and a decreased capillary length were measured.

Adult↗

PubMed1979

Effect of polyamines on cell-free protein synthesizing systems from rat cerebral cortex, cerebellum and liver.

The naturally occurring polyamines spermine and spermidine stimulate in low concentrations the amino acid-incorporating activity of cell-free systems from cerebral cortex, cerebellum and liver from the rat to a significant degree, but in high concentrations they have strong inhibiting effects on these systems. Maximal polyamine stimulation is observed with suboptimal Mg2+ concentrations in the reaction mixtures; increasing Mg2+ to 15 mM results in an inhibition of cell-free protein synthesis by polyamines even at low concentrations. The stimulating effect of spermine and spermidine involves a facilitated binding of template RNA and aminoacylated tRNA to the ribosomes. In contrast, the aminoacylation of tRNA is not influenced. These data indicate that spermine as well as spermidine have regulatory functions during the translational process in cerebral cortex, cerebellum and liver. They seem to interact with ribosomal functions and to cause a shift in the optimal Mg2+ concentration required for the synthesis of brain and liver proteins.

Amino Acids↗

PubMed1979

[Effect of tissue hypoxia on the structure of cerebral cortex neurons (light--electron microscopic study)].

An examination of the cerebral cortex of rats exposed to sublethal doses of potassium cyanide has revealed changes in the neurons characteristic of the developing histotoxic hypoxia. The neurons of the large hemisphere cortex showed a pronounced hydropic reaction in their cytoplasm with prevalent involvement of the mitochondria. This form of the pathology was observed irrespectively of the duration of the animals live after the poisoning. In rats which survived for a longer time there appeared hyperchromic neurons the number of which gradually increased. This fact was interpreted as addition of the hypoxic state of the neurons to the cyanide intoxication: this was confirmed by development of signs characteristic of hypoxic hypoxia at this stage. The degree of the changes in the mitochondria was found to correlate with the depth of the impairment of vitally important neuron structures. The data obtained show that the primary morphological changes in the neurons develop in their cytomembranes. The degree of the impairment of the mitochondrial membranes can serve as a criterion of reversibility or irreversibility of the pathological process in the nerve cells.

Animals↗

PubMed1976

The incorporation of radioactive fatty acids and of radioactive derivatives of glucose into the phospholipids of subsynaptosomal fractions of cerebral cortex.

1. Crude synaptosomal fractions (P2) from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium containing labelled fatty acids and [3H]glucose. After the shortest incubation period (7.5 min) a high percentage (50-80%) of the total radioactive fatty acids was found in the P2 fractions. 2. After the incubation, the synaptosomal fractions were submitted to hypo-osmotic disruption and subsynaptosomal fractionation was carried out by using discontinuous-sucrose-gradient centrifugation. The specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomal preparation) and H (disrupted synaptosomes), as were the specific activities of a number of marker enzymes and the distribution of acetylcholine. 3. By using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose, the order to specific radioactivities in fraction D was found to be: phosphatidylinositol greater than phosphatidylcholine greater than phosphatidylserine greater than phosphatidylethanolamine. 4. The specific radioactivities of phosphatidylcholine and phosphatidylethanolamine were always higher in fraction D than in fraction E. As fraction E had higher specific activities of several membrane marker enzymes, the enhanced labelling found in fraction D was considered to be localized in the synaptic vesicles. In this fraction, phosphatidylinositol made particularly large contributions to the total phospholipid labelling derived from [14C]arachidonate and [3H]glucose. 5. The similar labelling ratios of fatty acid/glucose in the phospholipids of fractions D and E, and the high specific radioactivities in the total phospholipid of the soluble fraction O, suggested intrasynaptosomal phospholipid transport.

Acetylcholine↗

PubMed2025

A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro.

Natural selection has shaped the gene regulatory networks that orchestrate cortical development, leading to structural and functional variation across mammals, but the molecular and cellular mechanisms underpinning these changes have only begun to be characterized. Here, we develop a reproducible protocol for cerebral cortex organoid generation from mouse epiblast stem cells (EpiSCs), which recapitulates the timing and cellular differentiation programs of the embryonic cortex. We generated cortical organoids from F1 hybrid EpiSCs derived from crosses between laboratory mice (C57BL/6J) and four wild-derived inbred strains spanning ∼1 M years of evolutionary divergence to comprehensively map cis-acting transcriptional regulatory variation across developing cortical cell types, using single-cell RNA sequencing (scRNA-seq). We identify hundreds of genes that exhibit dynamic allelic imbalances, providing the first insight into the developmental mechanisms underpinning changes in cortical structure and function between subspecies. These experimental methods and cellular resources represent a powerful platform for investigating gene regulation in the developing cerebral cortex.

Organoids↗