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Isolated catecholaminergic projections from substantia nigra and locus coeruleus to caudate, hippocampus and cerebral cortex formed by intraocular sequential double brain grafts.

Sequential intraocular grafting of defined areas from fetal rat brain to adult host rats was used to explore the possibility that such double grafts would become interconnected. Norepinephrine- containing neurons of the locus coeruleus were grafted together with either parietal cerebral cortex, hippocampus, or the caudate nucleus. Dopamine-containing neurons of the substantia nigra were transplanted together with either parietal cerebral cortex or the caudate nucleus. The brainstem grafts showed good survival and development in oculo, using both histochemical and electrophysiological criteria. Locus coeruleus neurons were found to innervate cerebral cortex, hippocampus, and the caudate nucleus. Substantia nigra neurons invaded cerebral cortex abundantly, with a terminal distribution typical of cortical DA terminals in situ. The innervation of the caudate nucleus from substantia nigra transplants was variable, but areas of dense confluent terminals were observed. We conclude that sequential brain grafting in oculo permits generation of isolated yet defined catecholaminergic projections, which are suitable for electrophysiological, pharmacological, and histochemical studies.

Animals↗

Lewy bodies in cerebral cortex, report of three cases.

The histochemical and structural properties and the topographical distribution pattern of Lewy bodies in the cerebral cortex as well as in the brain stem and diencephalon were studied in three cases. The Lewy bodies in the cerebral cortex were found in the small or medium-sized neurons of the fifth and sixth layers, particularly in the anterior frontal, temporal, insular, and cingulate cortex, and showed minor differences in their histochemical and structural properties from typical Lewy bodies in the brain stem and diencephalon. By light microscopy they were more irregular in shape, less eosinophilic, less sharply demarcated, and did not have clear halos and central cores. From the ultrastructural aspect, the filaments in them did not radiate, but were arranged at random, and circular profiles were not associated in the central zone. This type of Lewy body was also distributed in the basal ganglia. A close relationship between Lewy bodies and monoamines in the cerebral cortex of our cases was not recognized. These three cases showed also concomitant senile changes, i.e., senile plaques and neurofibrillary tangles.

Aged↗

Organizational levels of the cerebral cortex: an integrated model.

We propose a theoretical model of the cerebral cortex which is based on its cellular components and integrates its different levels of organization: (1) cells have general adaptive and memorization properties; (2) cortical columns are repetitive interneuronal circuits which determine an adaptive processing specific to the cerebral cortex; (3) cortical maps effect selective combinations which are very efficient to learn basic behavioural adaptations such as invariant recognition of forms, visually-guided hand movements, or execution of structured motor programs; (4) the network between cortical areas has a global architecture which integrates successive learning experiences into coherent functions such as the human language.

Cerebral Cortex↗

Release of vasoactive intestinal peptide in mouse cerebral cortex: evidence for a role of arachidonic acid metabolites.

In rodent cerebral cortex, vasoactive intestinal peptide (VIP) is contained in a homogeneous population of radially oriented bipolar interneurons. We have observed that 4-aminopyridine (4-AP), a K+-channel blocker, promotes a concentration- and Ca2+-dependent release of VIP from mouse cerebral cortical slices, with a significant effect already observed at 50 microM. Over 70% of VIP release elicited by 4-AP is blocked by 2 microM tetrodotoxin (TTX). Mepacrine, an inhibitor of phospholipase A2 (PLA2) activity and hence of arachidonic acid (AA) formation from membrane phospholipids, markedly inhibits (IC50 of approximately 15 microM) the release of VIP evoked by 4-AP. The inhibitory effect of mepacrine is not additive to that of TTX, thus indicating an involvement of PLA2 activation in the TTX-sensitive component of the 4-AP-evoked release. As a corollary, melittin (0.1-10 micrograms/ml), a PLA2 activator, promotes VIP release. Inhibition of AA metabolites of the lipoxygenase pathway by nordihydroguaiaretic acid, 5,8,11,14-eicosatetranoic acid, and caffeic acid results in a concentration-dependent inhibition of VIP release evoked by 4-AP. This set of observations indicates for the first time that the formation of AA metabolites of the lipoxygenase pathway plays a role in the release of a peptide in the mammalian CNS. Furthermore, these observations together with the previously reported potentiation by prostaglandins of the increase in cyclic AMP elicited by VIP in mouse cerebral cortex (Schaad et al., 1987) indicate that AA metabolites may act at both the presynaptic (lipoxygenase metabolites) and the postsynaptic (cyclooxygenase metabolites) levels to increase the "throughput" or "strength" of VIP-containing circuits in the rodent neocortex.

4-Aminopyridine↗

Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo.

1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/- 0.04%, P less than 0.05) the potassium-evoked release. 3. Neither quinolinate nor NMDLA had any effect on the basal efflux of endogenous amino acids from rat cortical slices either in the presence or absence of magnesium ions at concentrations between 10 microM and 5 mM. 4. Both NMDLA (1 mM) and quinolinate (5 mM) produced an efflux of endogenous aspartate (371.4% +/- 11.6%; 389.3% +/- 12.1%) and glutamate (405.4% +/- 13.6%; 430.1 +/- 8.7%) respectively from the rat cerebral cortex in vivo (P less than 0.01). The quinolinic acid-evoked efflux was abolished by the NMDLA antagonist, 2-amino-5-phosphonovaleric acid (200 microM). 5. Kainic acid also caused an efflux of endogenous amino acids from the rat cerebral cortex in vivo. However, the profile of this release was different from that produced by quinolinate and NMDLA. 6. The results add further support to the suggestion that quinolinic acid acts at the NMDLA-preferring receptor and may also explain the requirement for intact afferent projections for the neurotoxic effects of quinolinate to be manifested.

2-Amino-5-phosphonovalerate↗

Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices.

It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 microCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

Acute Disease↗

Steroid hormone effects on NMDA receptor binding and NMDA receptor mRNA levels in the hypothalamus and cerebral cortex of the adult rat.

Previous work has demonstrated that N-methyl-D-aspartate (NMDA) is capable of stimulating luteinizing hormone release in a variety of species. Interestingly, the ability of NMDA to stimulate luteinizing hormone release is significantly compromised in castrated male and female rats as compared to intact animals. The purpose of the present study was to determine if a difference exists in the number or affinity of NMDA receptors in the hypothalamus of intact or castrated adult male and female rats and whether steroid replacement has any effect on NMDA receptor binding. NMDA receptor mRNA levels were also determined in the respective models. The cerebral cortex was used as a control to check for specificity of any observed differences. The number of NMDA binding sites in the hypothalamus was found to be approximately 25% of that found in the cerebral cortex and the equilibrium association constant was similar in both tissues. In the female rat, neither ovariectomy nor ovariectomy with estrogen pellet replacement or estrogen and progesterone injections altered NMDA receptor binding or the equilibrium association constant in the hypothalamus or cerebral cortex as compared to intact controls. Similar to the case in the female, NMDA receptor binding in the hypothalamus and cerebral cortex of male rats did not change after castration or after treatment with testosterone propionate. Neither ovariectomy nor ovariectomy with estradiol replacement brought about any change in the NMDA receptor mRNA levels in the hypothalamus. However, in the cerebral cortex ovariectomy with estrogen replacement brought about a small but significant increase in NMDA receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

New observation on ubiquitinated neurons in the cerebral cortex of multiple system atrophy (MSA).

To investigate neuronal damage in the cerebral cortex in patients with multiple system atrophy (MSA), immunohistochemical stainings were carried out on the prefrontal cortex, the hippocampus, the precentral gyrus, the supplementary motor cortex and the occipital cortex in 6 cases of MSA and 6 controls, using antibodies against ubiquitin, tau protein and neurofilaments (BF10, RT97, 147). In MSA cases, a variable number of neuronal ubiquitinated inclusions were observed in the granule cell layer of the dentate gyrus (3/6) and the prefrontal cortex (3/6). An increased number of ubiquitinated dots-like structures were also observed in the parahippocampal gyrus of MSA cases (4/6) in comparison with controls. These results showed further evidence of neuronal damage in the cerebral cortex in MSA and strongly suggest a relationship between the cerebral cortical pathology and occasional manifestation of cognitive deficits in some MSA cases.

Atrophy↗

[The cerebral cortex regulates immune responses in the mouse].

Ablation of the left cerebral cortex abrogates the production of thymic hormone, reduces the number of spleen T cells and impairs immunization with sheep erythrocytes. In addition, partial decortication inhibits the ability of sodium diethyldithiocarbamate (DTC) to increase the level of circulating thymic hormone, as well as the number of splenic T cells. Therefore, the cerebral cortex would display an important role to maintain body integrity and relations with the external environment, through its effects on the immune system.

Animals↗

Expression of the high-affinity glutamate transporter EAAT4 in mammalian cerebral cortex.

RT-PCR, immunocytochemistry and Western blotting were used to study the expression of the glutamate transporter EAAT4 in the cerebral cortex of cat and mouse. By means of RT-PCR we were able to detect EAAT4 mRNA in the cerebral cortex of both species. Sequencing ensured the specificity of the amplified fragment. Immunocytochemistry and Western blotting enabled us to localize EAAT4 protein in cat and mouse cerebral cortex. Intense EAAT4 immunoreactivity was found in the soma and dendrites of neurons mainly of layers II, III and V. For both species, the signal in the cerebellum was very intense and confined to the molecular and Purkinje cell layer.

Amino Acid Transport System X-AG↗

Different volume changes of cerebral cortex and white matter during histological preparation.

In quantitative neuroanatomy and neuropathology, large neuronal systems are frequently analyzed on the basis of small tissue blocks thus assuming that the volume changes of the various compartments of the tissue block can be corrected by an overall factor. 228 blocks of cerebral cortex and white matter of the frontal lobe, thalamus, and striatum were prepared from 13 human brains and embedded in paraffin. The mean shrinkage in the paraffin sections was found to be 51% for the cerebral cortex and 42% for the white matter. Therefore, an overall correction factor tissue blocks both with cerebral cortex and white matter results in an underestimation of cerebral cortex and an overestimation of white matter.

Adult↗

Diurnal variations of benzodiazepine binding in rat cerebral cortex: disruption by pinealectomy.

In a previous work, pinealectomy was found to depress benzodiazepine (BZP) receptor binding in cerebral cortex membranes of rats killed at noon. In order to assess the effect of pineal removal on diurnal variations of BZP binding site concentration and affinity, groups of intact, pinealectomized, or sham-pinealectomized rats (subjected to surgery 2 wk earlier) were killed at six different time intervals during the 24-h cycle. BZP binding was assessed by Scatchard analysis of 3H-flunitrazepam high-affinity binding to cerebral cortex membranes. In intact and sham-pinealectomized rats, a maximum in BZP receptor concentration was found at midnight. Pinealectomy blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon. No changes in the affinity of the binding sites for the radioligand were detected as a function of time of day or following surgery. In a dose-response experiment for melatonin ability to restore the depressed BZP receptor concentration of cerebral cortex membranes of pinealectomized rats killed at noon, a minimal effective dose of 25 micrograms/kg body weight was obtained. These results further support a link between pineal activity and brain BZP receptors in rats.

Animals↗

T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex.

The mechanisms that regulate regional specification and evolution of the cerebral cortex are obscure. To this end, we have identified and characterized a novel murine and human gene encoding a putative transcription factor related to the Brachyury (T) gene that is expressed only in postmitotic cells. T-brain-1 (Tbr-1) mRNA is largely restricted to the cerebral cortex, where during embryogenesis it distinguishes domains that we propose may give rise to paleocortex, limbic cortex, and neocortex. Tbr-1 and Id-2 expression in the neocortex have discontinuities that define molecularly distinct neocortical areas. Tbr-1 expression is analyzed in the context of the prosomeric model. Topological maps are proposed for the organization of the dorsal telencephalon.

Amino Acid Sequence↗

High affinity 3,5,3'-L-triiodothyronine binding to synaptosomes in rat cerebral cortex.

Studies were undertaken to define the existence of specific T3-binding sites in the synaptosomal fraction of rat cerebral cortex. Development-related changes of the synaptosomal T3-binding sites were compared with those of nuclear T3 receptors in rat cerebral cortex. Scatchard analysis was compatible with the existence of two sets of high affinity T3-binding sites: K1, with a mean (+/- SE) apparent dissociation constant (Kd) of 3.22 +/- 0.63 x 10(-11) M and a mean (+/- SE) maximum binding capacity (MBC) of 3.2 +/- 0.3 pg T3/mg protein, and K2, with a K4 of 2.64 +/- 0.15 x 10(-9) M and a MBC of 218.3 +/0 15.0 pg T3/mg protein. When compared to T3, 27-, 135-, 500-, and 1000-fold higher concentrations of T4, 3,5-diiodothyronine (3,5-T2), triiodothyroacetic acid, and rT3, respectively, were needed to obtain 50% depression of the synaptosomal T3 binding. Tetraiodothyroacetic acid, 3,3'-T2, 3'5'-T2, 3-monoiodothyronine (3-T1), 3'-T1, and thyronine had little effect. The MBC of T3 nuclear receptors was the highest at 2 days of age and significantly decreased thereafter, although an almost constant K4 was observed in all age groups studied. On the contrary, the MBC of the higher affinity synaptosomal T3-binding sites was low in 2-day-old rats (20.3 +/- 1.2 pg T3/g tissue) and increased thereafter to the level in young adult ras (50.4 +/- 2.2 pg T3/g tissue). However, the Kd of synaptosomal T3-binding sites was also unchanged in all age groups studied. These findings clearly indicate that there exist specific T3-binding sites in synaptosomes from rat cerebral cortex.

Aging↗

Inhibitory effect of nociceptin on [3H]-5-HT release from rat cerebral cortex slices.

1. The effect of nociceptin (NC) on 5-hydroxytryptamine (5-HT) release was studied in rat cerebral cortex slices preincubated with [3H]-5-HT and electrically stimulated (3 Hz, for 2 min) at the 45th (St1) and the 75th (St2) min of superfusion. 2. NC (0.1 - 3 microM), present in the medium from the 70th min onward, concentration-dependently reduced electrically evoked [3H]-5-HT efflux (pEC50=6.54, Emax -54%). The inhibition was not antagonized by naloxone (1 microM) ruling out the involvement of opioid receptors. 3. Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2, which acts as an opioid-like receptor (ORL1) antagonist at the peripheral level, behaved as a partial agonist in cerebral cortex slices i.e. it inhibited [3H]-5-HT efflux when added before St2, however, when present in the medium throughout the whole experiment, [Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2 prevented the action of NC added at the 70th min. 4. The non-selective ORL1 receptor antagonist, naloxone benzoylhydrazone (3 microM), in the presence of 10 microM naloxone, did not modify the St2/St1 ratio but completely abolished the NC effect. 5. These findings demonstrate that NC inhibits 5-HT release from rat cerebral cortex slices via ORL1 receptors, suggesting its involvement in central processes mediated by 5-HT.

Animals↗

Cytoarchitecture of sensorimotor areas in the cat cerebral cortex.

The organization of multiple motor areas in the cerebral cortex has been investigated frequently in primates but rarely in nonprimate species. To compare sensorimotor areas in cats and primates, the cytoarchitecture of frontal and parietal areas of the cat cerebral cortex was described and mapped from coronal sections stained with cresyl violet or thionine. Multiple subdivisions of areas 4 and 6 were recognized; of these, the cytoarchitecture of area 4 gamma is similar to that of area 4 described in other carnivores and in primates and is characterized by giant pyramidal cells in multiple rows or clusters in lamina V. In other subdivisions of area 4 (4 delta, 4sfu, and 4fu), giant pyramidal cells are few or absent in lamina V, and these subdivisions resemble area 6 of primates. Area 6 of the cat cortex is heterogeneous, and differences in laminar appearance and size of pyramidal cells in lamina V distinguish its four subdivisions (6a alpha, 6a beta, 6a gamma, and 6iffu). The adjoining prefrontal areas are distinguishable from area 6 by the presence of a thin internal granular lamina (lamina IV) and the reduced size of pyramidal cells in lamina V. Laminae are poorly differentiated in the cingulate areas, where a rostral and caudal subdivision can be distinguished on the basis of the absence or presence of lamina IV. Area 3a is characterized by a thin lamina IV and is located between frontal agranular and parietal granular (well-defined lamina IV) fields (3b, 1, 2, 2pri, 5, and 7). Insular cortex can be subdivided into granular and agranular fields.

Animals↗

Nitric oxide synthase and cytochrome c oxidase changes in the tumoural and peritumoural cerebral cortex.

BACKGROUND: We analysed changes in nitric oxide synthase (NOS) and cytochrome oxidase (CO) activities in the tumoural and peritumoural cerebral cortex in order to investigate: a) the role of NO in tumourigenesis, in TBF regulation, and in vasogenetic PBE; b) the metabolic changes caused by the neoplasm in the surrounding tissues. METHOD: Intra-operative samples of cerebral cortex were studied by means of immunohistochemistry for nNOS and iNOS, and by histochemistry for NADPH-diaphorase (NADPH-d) and CO. FINDINGS: In contrast with normal cortex, reactive glial cells and the endothelium of small blood vessels displayed strong NADPH-d and iNOS activities in oedematous peritumoural tissue. In the tumoural cortex, NADPH-d and nNOS-positive neurones were reduced in number and their dendrites were thin and interrupted, and infiltrates of NADPH-d and iNOS-positive tumoural cells were frequent. CO activity was decreased in the deep layers of peritumoural cortex, and it was almost absent in the tumoural cortex. INTERPRETATION: In peritumoural and tumoural cortex changes in NOS and CO activities suggest that the coupling between neuronal activity and blood flow is impaired in the damaged cerebral cortex, and that the increase in NOS activity may play a role in tumour vascularization and progression.

Adenocarcinoma↗

Flattening the cerebral cortex by computer.

A computer program was developed for unfolding the cerebral cortex so that it could be viewed as a 2-dimensional surface. Input to the program consisted of tissue sections cut in a standard plane of section. Each section was represented by one line, which corresponded to a contour line in the flattened map. From these data, the computer constructed a 3-dimensional surface representation, which it then flattened. Because the cerebral cortex has considerable intrinsic curvature, flattening required that some regions be expanded and others shrunken. These changes occurred as a natural consequence of local decisions made by the computer as it laid down successive contours. The user could intervene during both surfacing and flattening in order to shape the developing map. The program has been used to generate 37 flattened maps from various regions of cat cortex, and 1 from monkey cortex. The local topography of cortical features such as gyri, sulci, architectonic boundaries, and patches of transported tracer, appeared to be conserved fairly faithfully. Areal distortion was also modest, with an average change in surface area of only 12%.

Animals↗