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PubMedDate not supplied

Noradrenergic innervation patterns in three regions of medial cortex: an immunofluorescence characterization.

A homologous antiserum directed against rat dopamine beta-hydroxylase (DBH was used for the immunohistofluorescent visualization of the noradrenergic (NA) innervation of medial cortex in the albino rat. Three cytoarchitectonic divisions of the medial cortex were studied: prelimbic (PL), anterior cingulate (AC), and granular retrosplenial (RSg). Each division of medial cortex possesses a characteristic and distinct pattern and density of NA fibers. The branching patterns and density of the fibers in PL cortex are similar to those of lateral cortex. AC cortex has the lowest density of NA innervation found in the neocortex; there is minimal arborization in layer I, and a very low density of fibers in layers II and III. In contrast RSg is the most densely innervated region, and NA fibers arborize extensively throughout all layers. The dopaminergic (DA) fibers in medial cortex were studied with glyoxylic acid-induced histofluorescence following midbrain lesions of the dorsal noradrenergic bundle (DNB). A laminar complementarity exists in AC cortex such that the DA fibers terminate in layers I-III, while the NA fibers are largely confined to the deep layers. The distinctive patterns of termination of coeruleocortical fibers indicate that in different cortical areas NA axons contact different elements of neuronal circuitry and that there is some degree of specificity in the distribution of NA terminals within the cortex.

Afferent Pathways↗

PubMed2006

Visceral-related area in the rat insular cortex.

The insular cortex interacts with the bulbar autonomic nuclei providing autonomic manifestations accompanying several neurological and psychosomatic disorders. The aim of our study was to identify the sites within the insular cortex, which could be responsible for the gastrointestinal, respiratory and cardiovascular responses. The main methods used were microinjections of HRP into several parts of the bulbar dorsal vagal complex and microstimulation of the insular cortex. It has been found that a compact group of neurons located in the middle level of the rat insular cortex projects directly to the specific "gastric" part of the dorsal vagal complex. Retrograde labelled cell bodies were revealed in the V layer of the disgranular and agranular insular cortex. Microstimulation of the sites within the middle level of the rat insular cortex produced gastric motor responses and a decrease in inspiratory airflow without significant alteration in respiratory cycle duration. More caudal microstimulation produced an increase in respiratory airflow and decreased respiratory cycle duration. These responses were usually accompanied by changes in the level of blood pressure. It is concluded that autonomic representation in the rat insular cortex is organised in a viscerotopic manner. The inhibitory respiratory zone overlaps with the gastrointestinal control area in the middle part of the insular cortex. More caudally, the excitatory respiratory zone overlaps with the cardiovascular area. On the basis of these experimental results and the data of others authors the general scheme of autonomic representation in the rat insular cortex is discussed.

Animals↗

PubMed2004

Leading role of the piriform cortex over the neocortex in the generation of spontaneous interictal spikes during block of GABA(A) receptors.

Interictal spikes are generated in the cerebral cortex during certain pathological conditions. In normal tissue, interictal spikes are triggered by blocking GABA(A) receptors. We studied the propensity of different areas of the cerebral cortex (including neocortex and piriform cortex) to generate spontaneous interictal spikes during block of GABA(A) receptors in slices of adult mice. Ten sequential brain slices were studied spanning most of the cerebral hemisphere. During block of GABA(A) receptors spontaneous interictal spikes were observed in all slices. Interestingly, interictal spikes recurred at different frequencies in different slices; posterior slices had a higher rate than the frontal slices (approximately 0.2 vs. 0.1 Hz, posterior vs. frontal). Multi-site recordings allowed to monitor discharges traveling across each slice and to derive cross-correlations. It became apparent that for the slices with higher frequency (i.e. posterior slices) the discharges originated in the piriform cortex and spread to the neocortex. A correlation between the frequency of the spontaneous discharges and the probability of events originating from piriform cortex was positive and significant. A further demonstration of this site of origin was provided by severing the connections between the neocortex and the piriform cortex. After interrupting these connections all the neocortical sites in the posterior slices displayed a lower frequency of discharges; similar to slower frontal slices. Meanwhile, the isolated piriform cortex of the posterior slices continued to produce higher frequency discharges. Thus, the higher frequency activity displayed by the posterior slices is intrinsically generated in the posterior piriform cortex from where it spreads to the neocortex. The results indicate that the neocortex and the piriform cortex have a distinct propensity to generate spontaneous interictal spikes, and that the more prone areas impose their activity on the less prone areas during disinhibition.

Animals↗

PubMed1987

Angiotensin converting enzyme predominates in the inner cortex and medulla of the rat kidney.

Regional distribution of angiotensin converting enzyme(ACE) in the rat kidney was studied. The ACE activities in the inner cortex and outer medulla were about 10 and 5 times those in the outer cortex, respectively. The activity in the inner medulla or papilla was much the same as that in the outer cortex. Immunofluorescence was greatest in the proximal tubules in the inner cortex, while the outer medulla and the inner medulla or papilla showed a weak fluorescence. The brush border membranes isolated from the inner cortex also possessed about 10 times the ACE activity seen in the outer cortex. The results indicate that the major source of renal ACE is not the proximal convoluted tubules in the outer cortex, but rather the brush border membranes of proximal tubules in the inner cortex. The contribution of ACE in the inner cortex would therefore be predominant.

Animals↗

PubMed2000

Directed sampling for electrolyte analysis and water content of micro-punch samples shows large differences between normal and ischemic rat brain cortex.

Changes in sodium, potassium, and water content in brain tissue are important in the progression of pathology that follows ischemic stroke. Determining these parameters regionally in rodent models of experimental ischemia has been limited because typical tissue weights of more than 35 mg are too large. Identifying ischemic tissue to direct tissue sampling towards ischemic cortex is also represents a difficult generally unresolved area. We suggest that larger differences between normal and ischemic cortex of sodium, potassium, and water content than previously observed can be obtained from directed sampling of 2-mg brain tissue in a model of focal cerebral ischemia. In five rats, the middle cerebral artery and both common carotid arteries were occluded for 4.9+/-0.13 h (mean+/-SEM). Punch-sampling of 1-mm diameter tissue cores for water content (H(2)O%) by the wet-dry method, and [Na(+)] and [K(+)] by flame photometry, was guided by the observation of a subtle change in the surface reflectivity of ischemic cortex of quickly dried, 20-microm frozen brain sections, that was confirmed by MAP2 immunohistochemistry. The ratio of the lesion areas as determined by the reflective change and MAP2 immunoreactivity was 0.96+/-0.03 (n=5). In ischemic cortex H(2)O% was 79.9%+/-0.8%, [Na(+)] was 550+/-25 mEq/kg dry-weight, and [K(+)] 94.2+/-19.2 mEq/kg dry-weight (n=5), all significantly different from the values in border zone cortex, and in cortex contralateral to ischemic cortex and border zone (for all samples n=60, mean wet weight 2.037+/-0.046 mg). Differences between ischemic and normal cortex were 5.4+/-1.1%, 317+/-21 mEq/kg dry-weight, -304+/-27 mEq/kg dry-weight (n=5) for H(2)O%, [Na(+)], and [K(+)]. These differences between ischemic and normal cortex are 1.4-2.5, 1-3.11, and 1.4-3.5 times greater, respectively, than previous results obtained using samples weighing 35 mg or more. These results extend the association of sodium and potassium with ischemic brain edema in the rodent model, and show that these classical measurements can keep pace with the regionality of histochemical and morphological methods.

Animals↗

PubMed2000

Effect of amphetamine on extracellular acetylcholine and monoamine levels in subterritories of the rat medial prefrontal cortex.

The present study sought to investigate the contributions of the dorsal prelimbic/anterior cingulate and ventral prelimbic/infralimbic cortices to the reverse microdialysis of amphetamine (1, 10, 100, 500, and 1000 microM) on dialysate acetylcholine, choline, norepinephrine, and serotonin levels. The results demonstrate that basal levels of acetylcholine, choline, and serotonin were homogeneous within subregions of the medial prefrontal cortex. In contrast, dialysate norepinephrine levels were significantly higher in the anterior cingulate cortex compared with the infralimbic cortex. Reverse microdialysis of amphetamine in both subareas of the medial prefrontal cortex produced a dose-dependent increase in norepinephrine and serotonin levels; the magnitude of this effect was similar in both subterritories of the medial prefrontal cortex. Microinfusion of amphetamine increased dialysate acetylcholine levels in a dose-dependent manner only in the infralimbic cortex. Finally, amphetamine decreased choline levels in both subregions of the medial prefrontal cortex. The magnitude of this effect was larger in the anterior cingulate cortex compared with its infralimbic counterpart. Since depletions of frontal cortical acetylcholine result in severe cognitive deficits, the present data raise the possibility that the type of neural integrative processes that acetylcholine mediates depends, at least in part, on the subterritories that characterize the medial prefrontal cortex.

Acetylcholine↗

PubMed2001

Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum.

Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in stimulating the release of dopamine in the striatum, whereas clozapine was much more effective in the medial prefrontal cortex. The efficacy of risperidone, olanzapine and ziprasidone did not differ for the two brain areas. The benzamides sulpiride and raclopride increased dopamine release in the striatum but did not affect the release of dopamine and noradrenaline in the medial prefrontal cortex. In the presence of dopamine/noradrenaline reuptake inhibitors, the benzamides strongly increased the release of dopamine-but not of noradrenaline-in the medial prefrontal cortex. The 5-HT(2) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (MDL100,907) (800 nmol/kg) and the dopamine D(2) receptor antagonist raclopride (2 micromol/kg) displayed a clear synergism in increasing the release of dopamine in the medial prefrontal cortex. No such synergism was seen in the case of noradrenaline. Co-administration of the 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine HCl (DOI) (850 nmol/kg) with clozapine (10 micromol/kg) or haloperidol (800 nmol/kg) blocked the increase in dopamine as well as noradrenaline in the medial prefrontal cortex. It is concluded that typical and non-benzamide atypical antipsychotics increase extracellular dopamine in the medial prefrontal cortex via a synergistic interaction by blocking 5-HT(2) as well as dopamine D(2) receptors. The increase in extracellular noradrenaline in the medial prefrontal cortex that was observed after administration of antipsychotics is explained by inhibition of 5-HT(2) receptors and not dopamine D(2) receptors. Finally, the significance of the classification of antipsychotic drugs based on their selective action on the release of dopamine and noradrenaline in the medial prefrontal cortex is discussed. In particular, the position of the benzamides is discussed.

Animals↗

PubMed2002

Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex.

Thyroid hormones are known to be important for optimal development of the human central nervous system. Classically, maternal thyroid hormones have not been thought to have a major role in defining central nervous system development. However, recent epidemiological evidence has indicated that subtle deficiencies in circulating maternal thyroid hormones in the first trimester of pregnancy are associated with adverse neurodevelopment. We have used real time PCR to quantitate the expression of mRNAs encoding the thyroid receptor isoforms (TR alpha1, alpha2, beta1 and beta2) and thyronine deiodinase subtypes (5'-DI, 5'-DII and 5-DIII) in human fetal cerebral cortex from the first and second trimesters of pregnancy. Deiodinase subtype activities have also been determined in these tissues and compared to 'normal' adult human cerebral cortex. Iodothyronine deiodinase mRNAs were expressed in human fetal cerebral cortex from 7 to 8 weeks of gestation. The expression of 5'-DI mRNA was variable in fetal life but increased relative to adult cortex (P<0.05), whereas the activity of this enzyme was below the level of assay detection. 5'-DII mRNA and activity in fetal cerebral cortex was detectable from as early as 7-8 weeks but not significantly different from that in adult life except at 15-16 weeks when mRNA expression increased (P<0.05). Fetal cortex 5-DIII mRNA expression was present from the early first trimester but less abundant than in adult tissue (P<0.01) and 5-DIII activity appeared greater in fetal cortex (P<0.01) as compared to adults. Only TR alpha1 mRNA was more abundantly expressed in fetal cortex than adult tissues (P<0.01). In contrast, the TR isoforms (alpha2 and beta1) were expressed significantly less than in adult tissues (P<0.05). Only 26% of fetal cerebral cortex samples expressed TR beta 1. There is evidence that the developing fetal brain, as early as the first trimester, expresses TRs and exhibits the mechanisms of pre-receptor control of thyroid hormone supply.

Adult↗

PubMed2000

Differential expression of S100B and S100A6(1) in the human fetal and aged cerebral cortex.

S100B and S100A6 (calcylin) are two members of the S100 Ca(2+)-binding protein family and have been localized in the mammalian nervous system. However, information on their distribution in the human nervous system, especially in the developing human fetal brain, is scarce. In the present study, an immunocytochemical method was used to examine the spatio-temporal protein expression patterns of S100B and S100A6 in normal human fetal hippocampus, entorhinal cortex and occipital cortex. Normal aged adult human brain specimens were also included for comparison. From week 15 onwards, an increase with advancing gestation age in both the number and staining intensity of S100B positive, astrocyte-like cells was found in the pyramidal layer of the hippocampus, while both the molecular and polymorphic layers showed similar S100B immunoreactivities at all stages examined. A decrease in the immunoreactivities was found in the molecular layer of the aged adult hippocampus while other layers exhibited immunoreactivities similar to those of the late fetus. At week 15, the molecular, pyramidal and ganglionic/multiform layers of the entorhinal cortex also showed positive S100B immunoreactivities which were maintained throughout the rest of the gestation and in adult specimens. In the occipital cortex, the numbers of positive cells for all layers were about twofold higher than those found in the hippocampus and entorhinal cortex, and immunoreactivities detected in the granular layer increased from week 21, reaching a plateau at around week 27. S100B positive fibers were also found at week 30 but were not observed in aged adult specimens. S100A6 positive cells were on the whole fewer in number than those of S100B in the brain regions examined. The S100A6 immunoreactivities which were localized in some pyramidal neuron-like and some glial-like cells of the pyramidal and molecular layers of the hippocampus increased by midgestation and became weak in the late fetus and in aged adult specimens. Weakly stained S100A6 positive cells were also observed in the entorhinal cortex throughout the gestation and in aged adult cortex. S100A6 immunoreactivities were weak in the fetal occipital cortex. They were also localized in the glial-like cells of the aged adult occipital cortex. The differential spatio-temporal expression of S100B and S100A6 proteins suggests that the proteins play different roles in different brain regions during development and in adulthood.

Aged↗

PubMedDate not supplied

A further evaluation of the effect of age on striate cortex of the rhesus monkey.

The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between 4 and 12 years of age with that of the eight monkeys over 25 years of age. The brains of the monkeys were all fixed by vascular perfusion and except for one of the old monkeys, whose age was estimated, the exact ages of all of the monkeys are known. One micron thick sections of plastic embedded cortex from one hemisphere of each monkey were examined by light microscopy to determine the thickness of the striate cortex, and neuronal frequency was determined by counting the numbers of neurons displaying nuclei in 250 microns-wide strips passing through the thickness of the cortex. When young monkeys were compared with the old ones, no differences were found in either the thickness of the cortex or in the numbers of neuronal profiles beneath unit areas of cortical surface. This suggests that neurons are not lost with age, and when the cortices were examined by electron microscopy there was no indication that the cell bodies of neurons are degenerating, except possibly in layer 1. Serial, 30 microns-thick, Nissl stained frozen sections from the other hemisphere of each monkey were used to determine both the surface area and the volume of the striate cortex. Overall, the surface area varied between 702 and 1480 mm2, with a mean value of 956 mm2, but there was no indication that the surface area decreased with age, and the same is true for the volume of striate cortex. The conclusion is that while there is a large variation in the amount of cortex occupied by area 17, there is no indication that its thickness, volume, or number of neurons is altered by age.

Aging↗

PubMed2004

The functions of the orbitofrontal cortex.

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as taste) is reversed. This is an example of stimulus-reinforcement association learning, and is a type of stimulus-stimulus association learning. More generally, the stimulus might be a visual or olfactory stimulus, and the primary (unlearned) positive or negative reinforcer a taste or touch. A somatosensory input is revealed by neurons that respond to the texture of food in the mouth, including a population that responds to the mouth feel of fat. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex can impair the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when there are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face (and voice) expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion. The approach described here is aimed at providing a fundamental understanding of how the orbitofrontal cortex actually functions, and thus in how it is involved in motivational behavior such as feeding and drinking, in emotional behavior, and in social behavior.

Animals↗

PubMed2002

Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex.

The barrel cortex has yielded a wealth of information about cortical plasticity in recent years. Barrel cortex is one of the few cortical areas studied so far where plasticity can be examined from birth through to adulthood. This review looks at plasticity mechanisms in three periods of life: early post-natal development, adolescence and adulthood. Separate consideration is given to depression and potentiation mechanisms. Plasticity can be induced in barrel cortex by whisker deprivation. Single whisker experience leads to expansion of the area of cortex responding to the spared whisker. In early post-natal life, plasticity occurs in thalamocortical pathways, while later in adolescence, intracortical pathways become more important. Ablation of the spared whisker's barrel prevents expression of plasticity in the cortex. A row of lesions between the spared and an adjacent barrel prevents expression of plasticity in the adjacent barrel. This evidence, together with latency of response data and an analysis of pathways capable of inducing long-term potentiation (LTP) within barrel cortex, leads to the view that horizontal and/or diagonal pathways between barrels are responsible for plasticity expression. The mouse has become the most commonly mutated mammalian species and has a well-developed barrel cortex. Therefore, mutations can be used to study the role of particular molecules in experience-dependent plasticity of barrel cortex. Through this work, it has become clear that the major post-synaptic density protein, alpha-CaMKII, and its T286 autophosphorylation site are essential for experience-dependent plasticity. This points to a major role for excitatory transmission in cortical plasticity and raises the possibility that LTP like mechanisms are involved. Furthermore, transgenic mice carrying a reporter gene for CRE have provided evidence that CRE-mediated gene expression is also involved in barrel cortex plasticity. This view is supported by studies on alpha/delta CREB knockouts, and provides a starting point for studying the role of gene expression in experience-dependent cortical plasticity.

Age Factors↗

PubMed1999

Effects of partial dopamine loss in the medial prefrontal cortex on local baseline and stress-evoked extracellular dopamine concentrations.

A reduction in the activity of mesoprefrontal dopamine neurons has been suggested to play a role in the pathophysiology of schizophrenia. Indeed, a recent study indicates that the density of tyrosine hydroxylase-immunoreactive axons is decreased in the deep layers of the prefrontal cortex of schizophrenic subjects [Akil et al., (1999) Am. J. Psychiatry, in press]. To determine the impact of partial loss of prefrontal dopamine axons on the activity of the remaining dopamine axons, we examined the effects of 6-hydroxydopamine lesions of the medial prefrontal cortex on local extracellular dopamine concentrations in the rat. In rats sustaining an average 63% loss of tyrosine hydroxylase-immunoreactive axons and no loss of dopamine-beta-hydroxylase-immunoreactive axons in the medial prefrontal cortex (smaller lesion), the baseline extracellular dopamine concentration was reduced by 63+/-9%. Thirty minutes of tail pressure increased extracellular dopamine in the medial prefrontal cortex by a maximum of 1.28+/-0.28 pg in control rats, but only 0.74+/-0.18 pg in rats with smaller lesions. In rats sustaining an average 80% loss of tyrosine hydroxylase-immunoreactive axons and 25% loss of dopamine-beta-hydroxylase-immunoreactive axons (larger lesion), the baseline extracellular dopamine concentration in the medial prefrontal cortex did not differ from control values. In addition, the maximum stress-evoked increase in dopamine concentration was also similar to that observed in control rats (+1.04+/-0.28 pg). The stress-induced increase in extracellular dopamine in the medial prefrontal cortex of rats sustaining smaller and larger lesions may occur in the absence of a corresponding increase in dopamine synthesis in mesoprefrontal dopamine neurons. This proposal is supported by our observation that stress did not alter tissue or extracellular 3,4-dihydroxyphenylacetic acid concentrations in the medial prefrontal cortex of lesioned rats. These data suggest that moderate loss of tyrosine hydroxylase-immunoreactive axons in the prefrontal cortex is sufficient to reduce extracellular dopamine concentrations in this brain region. In addition, a further reduction in tyrosine hydroxylase-immunoreactive axons in the medial prefrontal cortex, combined with the loss of dopamine-beta-hydroxylase-immunoreactive axons, results in normal extracellular dopamine concentrations in this area. We propose that the latter effect is due to increased neurochemical activity of remaining mesoprefrontal dopamine axons and/or decreased clearance of extracellular dopamine due to loss of both dopamine and norepinephrine transporters.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Comparative aspects of the olfactory portion of the entorhinal cortex and its projection to the hippocampus in rodents, nonhuman primates, and the human brain.

The entorhinal cortex is a component of the hippocampal formation characterized by its projection to the dentate gyrus. Cortical input is relayed to the hippocampus through the entorhinal cortex. The entorhinal cortex can be recognized best in mammals, and it reaches its maximal importance in both human and nonhuman primates. In primates, but not in rodents, the olfactory projection from the olfactory bulb is the only direct sensory projection reaching the entorhinal cortex, where it defines a rostromedial subfield (olfactory subfield of the entorhinal cortex, EO). In this communication, we consider some comparative aspects of this projection in rodents, nonhuman primates, and human brains, in relation to the forward projection to the hippocampus. We base our analysis on the following three considerations: (1) Topology: Topologically, the entorhinal cortex lies medial to the rhinal fissure, well developed in all mammals except in humans. EO maintains the same topological relationship to the rhinal fissure in the three mammalian orders. (2) Cytoarchitecture: The rostromedial portion shows poorer lamination compared with caudomedial portions of the entorhinal cortex in the three mammalian orders examined. (3) Connectivity: In rodents, the olfactory projection covers the whole extent of the entorhinal cortex, whereas it decreases substantially in macaques, where it roughly covers 15% of the entorhinal cortex. The human EO as defined by topological and cytoarchitectonic criteria may be even less than in macaques. Interestingly, good evidence exists that all of these mammalian orders maintain the same topographical scheme of projection to the rostral end of the hippocampus.

Animals↗

PubMed1999

Abnormalities of retinal metabolism in diabetes or experimental galactosemia. VI. Comparison of retinal and cerebral cortex metabolism, and effects of antioxidant therapy.

Metabolic abnormalities observed in retina and in cerebral cortex were compared in diabetic rats and experimentally galactosemic rats. Diabetes or experimental galactosemia of 2 months duration significantly increased oxidative stress in retina, as shown by elevation of retinal thiobarbituric acid reactive substances (TBARS) and subnormal activities of antioxidant defense enzymes, but had no such effect in the cerebral cortex. Activities of sodium potassium adenosine triphosphatase [(Na,K)-ATPase] and calcium ATPase became subnormal in retina as well as in cerebral cortex. In contrast, protein kinase C (PKC) activity was elevated in retina but not in cerebral cortex in the same hyperglycemic rats. Dietary supplementation with an antioxidant mixture (containing ascorbic acid, Trolox, alpha-tocopherol acetate, N-acetyl cysteine, beta-carotene, and selenium) prevented the diabetes-induced and galactosemia-induced elevation of retinal oxidative stress, the elevation of retinal PKC activity and the decrease of retinal ATPases. In cerebral cortex, administration of the antioxidant diet also prevented the diabetes-induced decreases in (Na,K)-ATPase and calcium ATPases, but had no effect on TBARS and activities of PKC and antioxidant-defense enzymes. The results indicate that retina and cerebral cortex differ distinctly in their response to elevation of tissue hexose, and that cerebral cortex is more resistant than retina to diabetes-induced oxidative stress. The greater resistance to oxidative stress in cerebral cortex, as compared to retina, is consistent with the resistance of cerebral cortex to microvascular disease in diabetes, and with a hypothesis that oxidative stress contributes to microvascular disease in diabetes. Dietary supplementation with these antioxidants offers a means to inhibit multiple hyperglycemia-induced retinal metabolic abnormalities.

Animals↗

PubMed2001

NMDA-stimulated Ca2+ uptake into barrel cortex slices of spontaneously hypertensive rats.

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit hyperactivity disorder (ADHD), since it has behavioural characteristics that resemble the behavioral disturbances of ADHD, namely hyperactivity, failure to sustain attention, and impulsiveness. The aim of this study was to establish whether N-methyl-D-aspartate (NMDA) receptor function was altered in barrel cortex slices of 4- to 6- week-old SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. The barrel cortex was dissected from brain slices corresponding to antero-posterior coordinates 8.7-4.8 mm with reference to the Paxinos and Watson (1986) atlas and divided into rostral, middle, and caudal regions. 45Ca2+ uptake was stimulated by incubating test slices in buffer containing 100 microM NMDA for 2 min at 35 degrees C. Total 45Ca2+ uptake into the entire barrel cortex as well as uptake into all regions of SHR barrel cortex was lower compared to WKY. Basal uptake into the entire barrel cortex as well as uptake into rostral and caudal regions of SHR barrel cortex was lower than WKY but basal uptake into the middle region was the same for both strains. There was no difference between SHR and WKY in NMDA-stimulated 45Ca2+ uptake into barrel cortex slices except for significantly lower NMDA-stimulated uptake into the middle region of SHR barrel cortex compared to WKY. These findings suggest that calcium metabolism is disturbed in the somatosensory cortex of SHR but that NMDA receptor function is not altered.

Animals↗

PubMed2003

Medial prefrontal cortex suppression of the hypothalamic-pituitary-adrenal axis response to a physical stressor, systemic delivery of interleukin-1beta.

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

Adrenocorticotropic Hormone↗

PubMed2000

Quantitative MRI volumetry of the entorhinal cortex in temporal lobe epilepsy.

The entorhinal cortex (Brodmann's area 28) is located at the anterior aspect of the parahippocampal gyrus ventral to the amygdala and the hippocampus. It is reciprocally interconnected with the hippocampus via glutamatergic pathways. We investigated whether the entorhinal cortex is damaged in human temporal lobe epilepsy (TLE). The volume of the entorhinal cortex was measured using magnetic resonance imaging (MRI) in 36 patients with cryptogenic TLE and in 21 controls. The mean volumes of the entorhinal cortex on the focal side did not differ from controls. In 11 of 36 patients, however, the entorhinal cortex volume was reduced by 25%. Entorhinal volume correlated with hippocampal volume in TLE (ipsilaterally, r= 0.454, P<0.01; contralaterally, r = 0.340, P<0.05). Further, 64% of patients with 25% entorhinal cortex damage had ipsilateral hippocampal atrophy. On the other hand, right focal TLE patients with hippocampal atrophy had a 19% volume reduction of the ipsilateral entorhinal cortex (P<0.05). The volume of the entorhinal cortex correlated with the duration of TLE (r= -0.335, P< 0.05). The present study indicates that the entorhinal cortex might be damaged in a subpopulation of patients with cryptogenic TLE. In most cases, volume reduction was associated with hippocampal damage. These data suggest that entorhinal damage contributes to the symptomatology in TLE.

Adolescent↗