Maria Chiotelli

Postnatal development of the dopaminergic system of the striatum in the rat.

The dopaminergic innervation of the developing caudate-putamen (patches and matrix) and nucleus accumbens (shell and core) of the rat was examined with light and electron microscope immunocytochemistry, using antibodies against dopamine. Light microscopic analysis showed, in accordance with previous studies, that early in life, dopaminergic fibers were relatively thick and present throughout the striatum. Their distribution was heterogeneous, showing dense aggregations, the so-called dopamine islands. The pattern of innervation became more uniform during the third postnatal week with most of the dopamine islands no longer detectable. For electron microscopic analysis, parts of the caudate-putamen containing dopamine islands or matrix, and of the nucleus accumbens, from the shell and the core of the nucleus, were selected. This analysis revealed that symmetrical synapses between immunoreactive profiles and unlabeled dendritic shafts predominated throughout development but, at the late stages, symmetrical axospinous synapses also became a prominent feature. These findings indicate that: (1) although the caudate-putamen and the nucleus accumbens have different connections and functions, they exhibit similar types of dopaminergic synapses, and (2) the relatively late detection of dopaminergic axospinous synapses suggests that the development of the dopaminergic system in the striatum is an active process, which parallels the morphological changes of striatal neurons and may contribute to their maturation.

Noradrenergic innervation of the developing and mature visual and motor cortex of the rat brain: A light and electron microscopic immunocytochemical analysis

The noradrenergic (NA) innervation of the developing and adult visual and motor cortex of the rat was examined with light and electron microscopic immunocytochemistry by using antibodies against dopamine‐β‐hydroxylase. At birth, NA fibers were present in both cortical areas, appearing as two tangential streams, one above and the other below the cortical plate. During the subsequent weeks, these two streams arborized gradually innervating all cortical layers. The adult pattern of distribution was attained by postnatal day 14, but the density of innervation, which was higher in the motor than in the visual cortex, appeared similar to the adult by the end of the third postnatal week. Electron microscopic analysis revealed that a low proportion of NA varicosities (the highest value was 12% in the adult motor cortex in single sections) were engaged in synaptic contact, throughout development, in both areas examined. The overwhelming majority of these synapses were symmetrical, involving predominantly small or medium dendrites. This evidence suggests that transmission by diffusion is the major mode of NA action in the developing and adult cerebral cortex. Noradrenaline released in the rare synaptic junctions may act mainly to reduce the activity of its cortical targets. The results altogether provide morphologic evidence for an involvement of noradrenaline in the development of the neocortex and, along with earlier data on the serotonergic system, indicate that the monoaminergic systems are endowed with a specific anatomic organization in various areas of the brain. J. Comp. Neurol. 445:145–158, 2002.

Vascular network of the rat hippocampus is not homogeneous along the septotemporal axis.

Qualitative and quantitative image analysis of hippocampal vascular bed, after transcardial perfusion of India ink, reveals significant differences among hippocampal subfields and along the septotemporal axis of the rat hippocampus. Ventral hippocampus exhibits significantly higher levels of vascularization compared to dorsal hippocampus, which, however, is characterized by significantly higher capillary density. These results may explain the selective ischemia vulnerability of hippocampus along its septotemporal axis.

Noradrenergic innervation of the developing and mature septal area of the rat

ABSTRACT The noradrenergic innervation of the developing and mature septal area of the rat was examined with light and electron microscopic immunocytochemistry using an antibody against dopamine‐β‐hydroxylase. At birth, a small number of relatively thick noradrenergic fibers were found to innervate the lateral septum (mainly its intermediate part) and the nuclei of the vertical and horizontal limbs of the diagonal band of Broca. By postnatal day 7, a substantial increase in their density was observed. At this age some labeled fibers left the medial forebrain bundle and invaded the nucleus of the horizontal limb of the diagonal band. These fibers then ran in a ventrodorsal direction and innervated the nucleus of the vertical limb before entering the medial septum. Immunoreactive fibers were finer and more varicose than at birth. In the subsequent 2 weeks, the density of labeled fibers in the septal area was further increased. By postnatal day 21, the distribution pattern and density of the noradrenergic innervation appeared similar to the adult. In the adult, noradrenergic fibers exhibited more varicosities than in younger rats. Electron microscopic analysis revealed a low proportion (peaked at P7) of noradrenergic varicosities engaged in synaptic contacts throughout development. The overwhelming majority of these synapses were symmetrical, predominantly with small or medium‐sized dendrites. The present findings provide the morphological basis for the functional interactions between noradrenergic afferents and neuronal elements in the septal area. The low proportion of synaptic contacts found in this study suggests that noradrenaline may exert its action in the septal area mainly through transmission by diffusion (volume transmission), as has been suggested for other areas of the developing and adult brain. J. Comp. Neurol. 476:80–90, 2004.

Mast cells populations fluctuate along the spinal dura mater of the developing rat

The present study reveals developmental changes in the number, the phenotype and the distribution pattern of mast cells (MCs) along the cervical, the thoracic and the lumbar parts of the spinal dura mater. Postnatal infiltration of spinal dura by MCs does not appear to follow a sequential developmental pattern and meningeal MCs are unevenly distributed along the various parts of the examined dura. At each spinal level, areas most densely populated by MCs are the dorsal dura and the dural sleeves of the dorsal (sensory) spinal roots The developmental time course of the total MCs number is characterized by significant fluctuations in all three parts examined, with notable increases at P1, P4, P21 and P60 (peak value) for the cervical part, at P1 (peak value), P7 and P21 for the thoracic part and at P1, P7 (peak value) and P30 for the lumbar part. At P180, MCs number declines to 56%, 33% and 13% of the peak values for the cervical, the thoracic and the lumbar part, respectively. However, a different developmental pattern is followed by each subpopulation of MCs identified on the basis of their staining characteristics, namely connective tissue type mast cells (CTMCs), mucosal type or cells with characteristics of immature mast cells (MTMCs) and mixed type MCs, in each part examined. The findings may be of importance in elucidating physiological and pathological processes in the dura mater and the vertebral column.

Parallel development of blood vessels and mast cells in the lateral geniculate nuclei

The present study examined quantitatively developmental changes of the vasculature in the dorsal (dLGN) and the ventral (vLGN) lateral geniculate nuclei together with concomitant changes in the number of mast cells (MCs), known for their role in angiogenesis. Vascular network, marked after transcardial perfusion of India ink, and MCs detected with conventional histochemical techniques were examined at postnatal days (P) 1, 8, 14, 21, 31, 90 and 300 of Wistar rats. Quantitative analysis by means of an image analysis system showed age-dependent changes in both vascular parameters [vascular area and relative frequency (%) of capillaries and medium- and large-diameter vessels] and mast cells number in the developing dLGN and vLGN. Despite quantitative differences in the vascularization and MC infiltration between the two nuclei at some age points, MC number, vascular area and the percentage frequency of capillaries exhibited similar developmental time courses, especially up to the end of the first postnatal month. Both MC number and the capillary frequency reached maximal levels at P31 and declined thereafter, following a massive or a partial, respectively, decrease up to P300.

Developmental changes of mast cell populations in the cerebral meninges of the rat

It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21.

Developmental changes in the vascular network of the rat visual areas 17, 18 and 18a

The present study examines quantitatively the areal and the laminar fluctuations of the vascular network in the visual areas 17, 18 and 18a of the rat cerebral cortex, from postnatal day (P) 1 to P60. For this purpose, the detailed vascular networks of the visual areas, marked after transcardial perfusion of India ink, are analyzed with the use of an image analysis system in order to measure the total vascular density (VD) and the relative density of capillaries (CD), of medium (MD)- and large (LD)-sized vessels in combination with changes in the mean diameter of all three types of vessels. Comparative quantitative microscopy showed that both VD and CD do not exhibit significant interareal differences in the adult rat brain. However, while VD reaches adult values much earlier in area 18a (P21) than in areas 17 and 18 (P60), CD obtains adult values at P31 in areas 17 and 18a, but later (P60) in area 18. Maturation process of laminar VD, CD, MD and LD was not found to follow a simple (i.e. inside-out or mediolateral) sequence, and, in each cortical area, laminar fluctuations of vessels density revealed a complicated developmental pattern, which might be attributed to their changing structural and functional status. Developmental changes in the diameter of capillaries, examined in conjunction with concomitant changes of vascular and capillary density in each area, suggest the existence of angiogenesis in all three visual areas during the third postnatal week of age.