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M E Cavanagh

Publications and source records attributed to M E Cavanagh.

17 recordsLinked to original sources

Postnatal development of vasoactive intestinal polypeptide-containing neurons in the visual cortex of normal and dark-reared rats.

The effects of dark rearing on the distribution and density of vasoactive intestinal polypeptide (VIP)-containing neurons in the visual cortical areas (17, 18 and 18a) of rats during postnatal development were examined immunohistochemically. Two groups of Wistar rats, one reared under normal lighting conditions and the other in complete darkness from birth, were used. VIP neurons showed a fairly similar distribution in the three visual areas, being predominantly present in layers II and III. Their pattern of development was found to be similar in the normal and dark-reared animals and was characterized by a marked increase from postnatal day (P) 7 to P21, followed by a gradual diminution to 24-31% of peak densities. Counts of labeled neurons at all ages examined showed that their density was similar in both groups at P7 and P14, but progressively greater in dark-reared animals from P21 and thereafter, so that they only fell to 38-43% of peak densities. Thus, by 60 days of age densities of VIP-labeled neurons in areas 17, 18 and 18a in dark-reared rats were 57%, 49% and 51% higher than in the corresponding areas of the age-matched control rats. These results indicate that the normal decline in the numbers of VIP neurons is not so marked under the conditions of dark rearing.

Aging↗

Measurements of somatostatin and neuropeptide Y in the visual cortex of monocularly deprived rats.

The levels of somatostatin and neuropeptide Y were measured with radioimmunoassay bilaterally in visual cortical areas 17, 18, and 18a of rats which had received monocular enucleation at birth. Neuropeptide levels were consistently three- to fourfold higher for neuropeptide Y than for somatostatin. Monocular enucleation did not change somatostatin levels within areas 17 or 18 of either hemisphere but significantly increased somatostatin levels in contralateral area 18a when compared to contralateral areas 17 or 18 3 months after enucleation. The concentrations of neuropeptide Y are significantly greater in areas 17 and 18a than those in area 18, however, neonatal enucleation had no significant effect on neuropeptide Y levels within any visual cortical area of either hemisphere. Visual cortical areas 17, 18, and 18a show differences in the relative concentrations of neuropeptide Y compared to somatostatin. Furthermore, these two peptides respond distinctively to neonatal enucleation. Enucleation had no effect on the concentration of either peptide in samples of frontal cortex. Immunohistochemical analysis showed that area 17 contains far fewer somatostatin neurons than areas 18 or 18a, in marked contrast to the uniform levels of somatostatin measured in all visual cortical areas by radioimmunoassay. Immunohistochemically identified neuropeptide Y-immunoreactive neurons are evenly distributed between areas 17, 18, and 18a and represent about half of the number of somatostatin-immunoreactive cells. While neuropeptide Y levels are significantly different between these visual cortical areas, the numbers of immunoreactive neurons are similar. Thus, relatively few neuropeptide Y cells are accompanied four- to fivefold higher than those for somatostatin, the more abundant cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

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Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats.

The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I-III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14-19% of the peak levels. Although this decline was still obvious, it moderated to 25-31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in dark-reared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential.

Aging↗

Postnatal development of neuropeptide Y-containing neurons in the visual cortex of normal- and dark-reared rats.

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons in the visual cortical areas (17, 18 and 18a) has been studied in Wistar rats reared under normal lighting conditions or in complete darkness. Immunohistochemistry on paraffin sections at postnatal days (P)7, 14, 21, 30 and 60 showed an overall similarity in laminar distribution of NPY neurons in all 3 visual areas of both normal- and dark-reared animals. The pattern of development of NPY neurons was characterized by an increase in their density from P7 to reach a peak at P21 followed by a decline to 37-47% of peak levels at P60. However, this diminution was not so great in dark-reared rats as in the normal, since the density only decreased to 62-78% of peak levels. At P60 the resulting differences in neuron density were marked in areas 17 and 18, where the dark-reared had 75% more cells than normal, and moderate in area 18a (30% more than normal). These results suggest that the normal decline in NPY neurons is not entirely mediated by visual experience since it takes place, albeit to a modified extent, in its total absence.

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Proportion of glutamate- and aspartate-immunoreactive neurons in the efferent pathways of the rat visual cortex varies according to the target.

Immunohistochemistry, with antisera directed against glutamate (Glu) or aspartate (Asp), was combined with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) histochemistry to examine the distribution, morphology, and proportions of Glu- and Asp-containing neurons that give rise to corticofugal and callosal projections of the rat visual cortex. WGA-HRP injections in the dorsal lateral geniculate nucleus resulted in retrograde labelling of small and medium-sized cells throughout layer VI of the visual cortex. Of these cells, 60% were also Glu-immunoreactive and 61% Asp-positive. WGA-HRP injections in the superior colliculus labelled large and medium-sized neurons in the upper portion of layer V of the visual cortex. Of these cells, 46% were also stained for Glu and 66% for Asp. Injections in the pontine nuclei resulted in retrograde labelling of cells in the deeper part of cortical layer V. Retrogradely labelled cells, which were also immunoreactive for Glu or Asp, were large pyramidal cells. Corticopontine neurons, which were also Glu-positive, accounted for 42% of the total number of WGA-HRP labelled cells, whilst for Asp-positive neurons this percentage was 51%. Finally, after injections in the visual cortex, retrogradely labelled small and medium-sized cells were found throughout layers II-VI in the contralateral visual cortex. Of these neurons, 38% were also labelled for Glu while 49% were also Asp-immunoreactive. The present results demonstrate that substantial proportions of projection neurons in the rat visual cortex are immunoreactive for Glu or Asp, suggesting that these excitatory amino acids are the major transmitters used by the cortical efferent systems examined. Furthermore, the proportions of these immunoreactive neurons in the efferent pathways vary according to the target.

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Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital cortex: a combined immunohistochemical-autoradiographic study.

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E21, has been studied in the rat occipital cortex. Immunohistochemistry combined with autoradiography showed evidence of a modified "inside-out" pattern of maturation. NPY-neurons are generated between E14 and E20 and are found in layers II-VI of the cortex and the subcortical white matter. NPY neurons from all these birthdates are overproduced at first, although cells generated at E16 produce the greatest excess, followed by E15 and E17. Some of these transient neurons are found in the "wrong" layer for their birthdates, and their elimination produces a more "correct" alignment at maturity. However, most of the NPY neurons that survive are generated at E17, and these cells are found throughout layers II-VI with a preponderance in layer VI. This evidence is strongly suggestive of cell death rather than merely cessation of production of NPY.

Aging↗

Development of vasoactive-intestinal-polypeptide-immunoreactive neurons in the rat occipital cortex: a combined immunohistochemical-autoradiographic study.

The postnatal development of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E22, has been studied in the rat occipital cortex. Immuno-histochemistry combined with autoradiography showed very little evidence of an "inside-out" pattern of maturation. Most VIP neurons are generated between E17 and E21 and are found in layers II-IV of the cortex, but their position within these layers is not dictated by their date of birth. There is evidence of a temporal maturation since E17 VIP neurons were seen first (at day 7) and E21 last. Peak numbers of VIP neurons were generated on E19. The numbers of VIP-immunoreactive neuronal somata detected in the cortex increased from the first week after birth to the third week and declined thereafter. However VIP-immunoreactive dendrites were still visible, suggesting that VIP levels in the cell bodies were very low, and not that there was a loss of neurons.

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Development of somatostatin immunoreactive neurons in the rat occipital cortex: a combined immunocytochemical-autoradiographic study.

The postnatal development of somatostatin (SRIF)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E22, has been studied in the rat occipital cortex. Immunocytochemistry combined with autoradiography showed an "inside-out" maturation pattern. Only SRIF neurons generated at E14 were present in layer VI in newborn rats. Later generated SRIF neurons appeared progressively higher in the cortex until about postnatal day 12 when SRIF neurons from E21 appeared in layer II. At 2 weeks of age, therefore, all SRIF neurons from E14-E21 were present. Most of these had been generated between E15 and E17 with a moderate number at E14 and rapidly diminishing numbers from E18 to E21. Although an overall layered distribution was apparent at peak production, there was a tendency for diffuse distribution most noticeable at E17. Diffusely distributed neurons were more likely to be below their appropriate layer than above it, thus contributing extra SRIF neurons to layer VI. At 3, 4, and 5 weeks, progressively fewer SRIF neurons were seen with a consequent reduction in the number of double-labeled neurons. It is suggested that the transient population of SRIF neurons thus revealed plays a role in cortical development.

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Extensive co-existence of neuropeptides in the rat visual cortex.

The peroxidase-antiperoxidase immunohistochemical technique has been used to examine the co-existence of peptides within individual neurons of the rat visual cortex. Pairs of consecutive paraffin sections were stained alternately for 2 of the 4 peptides: somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and neuropeptide Y (NPY). Analysis revealed the co-existence of SRIF with VIP, CCK and NPY and between VIP and CCK. These results show that the co-localization of neuropeptides in cortical neurons is more widespread than previously demonstrated.

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The distribution of native albumin and foreign albumin injected into lateral ventricles of prenatal and neonatal rat forebrains.

Several plasma proteins are found within the cells of the developing brain of many species, with a distribution pattern which changes during development, but the origin of such proteins is in dispute. The experiments described here were designed to test the hypothesis that some developing brain cells are able to take up plasma proteins. The distribution of the plasma protein albumin has been studied in the rat forebrain from the 14th day of gestation until birth. Although present within the cerebrospinal fluid and plasma from the earliest age studied, albumin was not seen within cells of the developing forebrain until day 16E or 17E. A foreign protein, sheep albumin, was injected into the ventricles at days 14E, 16E, 18E, 20E and on the day of birth. Sheep albumin can be detected in the presence of rat albumin because the antibody to sheep albumin does not cross-react with rat albumin. The sheep albumin was taken up very rapidly into cells of the ventricular zone at the later but not the earlier ages, thus mimicking the distribution of the naturally occurring rat albumin. After the foreign albumin had been left within the ventricle for several hours, some of the cells of the cortical plate also contained the protein, again mimicking the normal distribution of albumin. These findings suggest that the presence of albumin within cells of the developing rat forebrain can largely be attributed to uptake rather than synthesis.

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Postnatal development of the telencephalon of the tammar wallaby (Macropus eugenii). An accessible model of neocortical differentiation.

The sequence of development of cell layers in the neocortex of the tammar has been followed from 24 days gestation to 213 days postnatal. The tammar is born at 27 days gestation and the major period of its development occurs during the subsequent 250 days, most of this time being spent within the pouch. Although the pattern of differentiation of the cell layers appears to resemble that described for many Eutherian mammals, the neocortex is at an embryonic 2 layered stage at birth and a cortical plate is not present throughout the telencephalon until 10-15 days postnatal. A transient subplate zone, presenting a characteristic appearance with widely spaced rows of cells aligned parallel to the cortical surface, develops between 20 and 70 days postnatal, but no secondary proliferative region is seen in the subventricular zone of the dorso-lateral wall. Preliminary experiments with (3H)-thymidine injections indicate that the cortical plate follows the "inside-out" pattern of development described in many Eutherian mammals and that the oldest neurons are found in the parallel cell rows of the subplate zone. The importance of the late differentiation of the neocortex in relation to the time of birth and the resulting usefulness of the tammar as an experimental model of cortical development is discussed.

Aging↗

An immunocytochemical study of the distribution of some plasma proteins within the developing forebrain of the pig with special reference to the neocortex.

The distributions of 4 plasma proteins (fetuin, transferrin, alpha-fetoprotein and albumin) have been studied by means of immunocytochemistry in the forebrain of the pig from 20 to 109 days of gestation, term being at 114 days. These proteins are present in plasma, cerebrospinal fluid, meninges, some epithelial cells of choroid plexus and some neural cells and processes. The most striking observation is that these proteins are excluded from the brain to a large extent even at the earliest ages. Fetuin is present early in gestation in a few cells bordering the ventricle. Fetuin-positive cells are subsequently seen principally in the newly formed cortical plate and later in the subplate zone. This suggests that fetuin may be acting as a signal for the early migrating cells of the cortex and that its presence is necessary to these cells, particularly as there appears to be an increase in the amount of fetuin in these same cells in mid-gestation at a time when many fibres are arriving in this region to make cortical connections. Late in gestation after connectivity, it has been established that there are few fetuin-positive neurons remaining. However, at this late stage many neurons are strongly positive for transferrin, for which they have been negative earlier. This appearance may be related to the onset of activity. Alpha-fetoprotein has a distribution similar to that of fetuin. Albumin, although present transiently in the cerebrospinal fluid in the middle of gestation, is not seen in neural cells within the cortex. There has been some controversy as to whether these proteins which have been reported to be present in the brains of other species have been synthesized by neural cells or been taken up by specific mechanism. This study suggests that during the course of brain development, both processes may play their part.

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CSF-brain permeability in the immature sheep fetus: a CSF-brain barrier.

The permeability of the neuroependyma between CSF and brain extracellular space has been studied in fetal sheep of 60 and 125 days gestation. Both radioactive ([3H]inulin, [14C]sucrose, [125I]albumin) and visible (horseradish peroxidase) markers have been perfused through the ventricular system for periods of up to 5 h in anaesthetized exteriorized fetal sheep whose physiological condition was monitored continuously. A previously undescribed barrier between CSF and brain extracellular fluid has been discovered in the immature (60-day) fetal sheep. Horseradish peroxidase penetration was confined to a limited depth of the neuroependyma and was mainly into the cells lining the cerebral ventricles; in older fetuses there was extracellular penetration to a distance of several millimetres from the ventricular surface, as previously described in adult animals. The volumes of distribution of sucrose and insulin were less in the immature brain than in the more mature brain, which may be a reflection of restricted diffusion across the neuroependyma in the younger brains. The morphological nature of the barrier in fetuses of 60 days and younger appears to be a membrane specialization between the cells of the neuroependyma. It is of a type not previously described; it seems to have the effect of narrowing rather than obliterating the extracellular pathway between CSF and brain. The possible functional significance of this observation is discussed.

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Comparison of proteins in CSF of lateral and IVth ventricles during early development of fetal sheep.

This study examines the relationship between plasma proteins in blood and in CSF in the developing brain of sheep fetuses between 30 and 60 days gestation. Five proteins account for the very high concentration of protein in fetal CSF (over 1000 mg/100 mg/100 ml at 30 days): alpha-feto-protein, fetuin, albumin, alpha 1-antitrypsin and transferrin; the concentration of each protein is similar in lateral and IVth ventricular CSF at 30 days. By 40 days there is considerable decrease in protein concentration in lateral ventricular CSF. At this age in the IVth ventricle the overall total was unchanged, although there were changes in concentration of individual proteins. At 60 days the concentration of each protein in both compartments had fallen below that at 40 days; the marked concentration difference between lateral and IVth ventricular CSF was still present. Experiments using i.v. [125I]- or [3H] labeled plasma proteins in 30-40-day fetuses showed that very little protein penetrated into lateral ventricular CSF by 3-5 h after injection; in the same experiments [125I]albumin reached a CSF/plasma ratio of about 15% in the IVth ventricle (compared with 55% for the natural steady state). Autoradiographic studies carried out on material from the same animals did not give evidence for transfer of labeled protein across the choroid plexuses although any such penetration may have been below the threshold of the method. Other explanations for the high concentration of protein in CSF that were considered include penetration via cerebral vessels and synthesis of plasma proteins by choroid plexus epithelial cells or neurons within the brain.

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Proteins in cerebrospinal fluid and plasma of fetal pigs during development.

The concentrations of total protein, alpha-fetoprotein, fetuin, transferrin and albumin have been measured in cerebrospinal fluid (CSF) and plasma of fetal pigs from 26 to 109 days gestation. Plasma total protein concentration was lowest in the youngest fetuses but thereafter it was between 1,500 and 2,200 mg/100 ml. alpha-Fetoprotein was the predominant plasma protein early in development but its concentration declined throughout the fetal period. alpha-Fetoprotein, fetuin and transferrin accounted for over 65% of the total protein concentration at all fetal ages. Albumin was not detectable in either plasma or CSF at 26 days and did not account for more than 10% of total plasma protein concentration at later stages of gestation; in contrast fetuin was the major protein in plasma (and CSF) later in fetal development. In CSF the concentration of fetuin was highest (178 +/- 8 mg/100 ml) at 26 days. The concentrations of total protein (961 +/- 95 mg/100 ml), alpha-fetoprotein (406 +/- 77 mg/100 ml) and transferrin (195 +/- 19 mg/100 ml) were highest at 31 days after which the concentration of all the main proteins fell very considerably. Albumin was first detected in CSF at 38 days and contributed less than 10% of total protein concentration at later fetal ages. Possible origins of plasma proteins in fetal CSF are discussed. Differences in CSF: plasma ratios for different proteins are consistent with a specific transfer mechanism between their two compartments; but synthesis by fetal choroid plexus or brain has not been excluded.

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