H.J. ten Donkelaar

Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer's disease

Marked neuron loss in the nucleus basalis of Meynert complex (NBMC) in Alzheimers disease has repeatedly been reported in the literature. However, most of these studies quantitated only magnocellular, hyperchromatic (putative cholinergic) neurons of just a small part of the NBMC, and counts were expressed as numerical density. Applying a 3-dimensional-sampling design throughout the entire rostrocaudal extent of the NBMC and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of only 15.5% was demonstrated for the whole NBMC. Neuron loss varied from 0% rostrally in the NBMC up to 36% in the most caudal part of the nucleus basalis of Meynert. Moreover, a significant increase in the number of small-sized neurons and a significant decrease in the number of large, putative cholinergic neurons could be detected, suggesting that apart from neuron loss neuron shrinkage appears to be another characteristic neuropathological feature of this degenerating cholinergic NBMC system. Preservation of these magnocellular cholinergic neurons in shrunken form renders it likely that cholinergic dysfunction, characteristic of Alzheimers disease, may be responsive to neurotrophic influences.

Cells of origin of descending pathways to the spinal cord in the clawed toad (Xenopus laevis).

Abstract The cells of origin of pathways descending to the spinal cord in the clawed toad Xenopus laevis have been demonstrated with the horseradish peroxidase technique. A technique has been used taking advantage of the phenomenon that damaged axons can take up horseradish peroxidase and transport this enzyme to their parent cell bodies. The following descending supraspinal pathways could be demonstrated: a striatospinal pathway to the rostral part of the cord; distinct hypothalamospinal projections; a projection as far as the lumbar cord from the ventral thalamic nucleus; distinct projections from the mesencephalic tegmentum; a contralateral cerebellospinal projection from the cerebellar nucleus; a projection from neurons directly medial to the nucleus isthmi which shows resemblance to the coeruleospinal pathway of higher veretebrates; massive reticulospinal projections; a vestibulospinal projection arising in the nucleus ventralis VIII and pathways arising in nuclei receiving lateral line afferents. Furthermore, spinal projections from the nucleus of the solitary tract and the nucleus descendons nervi trigemini were observed. Rather massive projections were found to arise in the midbrain tegmentum: a mainly ipsilateral projection from the interstitial nucleus of the fasciculus longitudinalis medialis, a contralateral projection as far as the lumbar cord from a cell group which presumably represents the anuran homologue of the red nucleus of higher vertebrates, and projections from various other parts of the midbrain tegmentum, mainly to more rostral levels of the cord. Only a very small tectospinal projection could be demonstrated. A comparison with experimental data in higher vertebrates makes it likely that the pathways demonstrated from the hypothalamus and brain stem in Xenopus laevis show remarkable similarities to pathways in reptiles, birds and mammals.

Evolution of the red nucleus and rubrospinal tract.

Abstract A red nucleus, defined by its relative position in the tegmentum mesencephali, its contralateral rubrospinal or rubrobulbar projections and by crossed cerebellar afferents, is found in terrestrial vertebrates and certain rays. A crossed rubrospinal tract occurs in anurans, limbed urodeles and reptiles, birds and mammals, but is apparently absent in boid snakes, caecilians and sharks. A distinct rubrospinal tract is found in certain rays which use their enlarged pectoral fins for locomotion. A crossed tegmentospinal tract, possibly a rubrospinal tract, is found in lungfishes. Although evidence was presented for a rubrospinal tract in more advanced snakes, the available experimental data in lower vertebrates suggest that the presence of a rubrospinal tract is related to the presence of limbs or limb-like structures. In the connectivity of the red nucleus in terrestrial vertebrates, ‘levels’ of complexity can be distinguished, paralleled by the development of the cerebellum. These ‘grades of organization’ are probably related to the type of motor performance the particular terrestrial vertebrates are capable of.

Organization of Descending Pathways to the Spinal Cord in Amphibians and Reptiles

Publisher Summary This chapter discusses the organization of descending pathways to the spinal cord in amphibians and reptiles. Non-mammalian vertebrates—such as amphibians and reptiles—show a considerable variation in form and mode of locomotion, which has remarkable repercussions in the central nervous system. In tailless amphibians, the spinal cord occupies only part of the vertebral canal. In tailed amphibians and reptiles, the cord extends throughout the vertebral column. Prior to the development of the modern tracer techniques, the descending pathways to the spinal cord could be experimentally verified by the following procedures: (1) recording the occurrence of retrograde cell changes following spinal cord hemisections and (2) studying the ensuing fiber and (pre)terminal degeneration after lesions placed in the forebrain, brain stem, or spinal cord. Reticulospinal neurons constitute the most primitive descending system involved in motor control in vertebrates. These neurons are usually large, and their coarse axons conduct rapidly and make direct connections with spinal motoneurons and interneurons in all classes from cyclostomes to mammals.

The development of serotonergic raphespinal projections in Xenopus laevis

The development of serotonin‐immunoreactive neurons in the central nervous system of Xenopus laevis larvae has been studied with special emphasis on the development of the raphe nuclei and raphespinal projections. The first serotonergic neurons were observed in the rostral part of the brain stem at stage 25, only 28 hr after fertilization. By stage 28 some 20 serotonin‐immunoreactive neurons were found in the rostral part of the brain stem, bearing small protrusions on the ventromedial side of the soma. These initial axonal outgrowths reach the rostral part of the spinal cord at stage 32. By stage 35/36 the growth cones of the descending serotonergic axons in the spinal cord have reached the level of the anus (10th to 15th myotome). Up to stage 45 the majority of the descending serotonergic axons was found in the dorsolateral part of the marginal zone of the spinal cord. After stage 45 some serotonergic axons were also found scattered over other parts of the spinal marginal zone. Collateral oranches were first observed in the caudal part of the brain stem at stage 35/36. Later they occurred also in the rostral (stage 43) and caudal (stage 50) spinal cord, usually on fibers in the ventral half of the spinal cord. The number of serotonergic neurons in the central nervous system (brain stem and hypothalamus) increased steadily throughout development until stage 45. After that the total number of serotonergic neurons in the central nervous system increased about two times faster than the number of serotonergic neurons in the raphe nuclei, due to a massive increase of serotonergic neurons in the hypothalamus.

Cell loss in the nucleus raphes dorsalis in alzheimer's disease

Marked neuron loss in the predominantly serotonergic nucleus raphes dorsalis (NRd) in Alzheimers disease (AD) has repeatedly been reported in the literature. However, most of these studies quantitated only part of the NRd and data were expressed as numerical density. Applying a 3-dimensional sampling scheme throughout the entire rostrocaudal extent of the NRd and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of 39.4% was demonstrated and a tendency for cell shrinkage was likely to be present. No rostrocaudal gradient in neuron loss could be shown. These NRd data are in accordance with neuron loss in other subcortical structures in AD.

Distribution of catecholamines in the brain stem and spinal cord of the lizard Varanus exanthematicus: an immunohistochemical study based on the use of antibodies to tyrosine hydroxylase

Antibodies to tyrosine hydroxylase were used to study the distribution of nerve cells, fibers and terminals, containing catecholamines, in the lizard Varanus exanthematicus, by means of the indirect immunofluorescence technique. Tyrosine hydroxylase-containing cell bodies occurred in the hypothalamus, the ventral and dorsal tegmentum mesencephali, the substantia nigra, the isthmic reticular formation, in and ventrolaterally to the locus coeruleus, in the nucleus tractus solitarii and in a lateral part of the nucleus reticularis inferior. In addition tyrosine hydroxylase-containing cell bodies were found throughout the spinal cord, ventral to the central canal. Tyrosine hydroxylase-immunoreactive terminal areas in the brain stem were seen in the nucleus interstitialis of the fasciculus longitudinalis medialis, the nucleus raphes superior, the locus coeruleus, several parts of the reticular formation and the nucleus descendens nervi trigemini. Ascending catecholaminergic pathways could be traced from the ventral mesencephalic tegmentum as well as from the dorsal isthmic tegmentum rostralwards, through the lateral hypothalamus. These pathways correspond to the mesostriatal and isthmocortical projections respectively, as described in mammals. Furthermore, ascending catecholaminergic fibers could be traced from the catecholaminergic cell groups in the medulla oblongata to the isthmus, where they intermingle with the locus coeruleus neurons. These pathways correspond to the medullohypothalamic projection and to the dorsal periventricular system in mammals. Descending catecholaminergic fibers to the spinal cord pass via the dorsomedial part of the lateral funiculus, and mainly terminate in the dorsal horn. The results obtained in the present study have been placed in a comparative perspective, which illustrates the constancy of catecholaminergic innervation throughout phylogeny.

Distribution of serotonin in the brain stem and spinal cord of the lizard Varanus exanthematicus: An immunohistochemical study

The distribution of serotonin-containing nerve cell bodies, fibers and terminals in the lizard Varanus exanthematicus was studied with the indirect immunofluorescence technique, using antibodies to serotonin. Most of the serotonin-containing cell bodies were found in the midline, in both of the raphe nuclei, i.e. the nuclei raphes superior and inferior. A considerable number of more laterally shifted serotonergic neurons was found particularly at three levels of the brain stem, viz. in the caudal mesencephalic tegmentum, at the isthmic level, and over a long distance in the medulla oblongata. These laterally situated serotonin-positive neurons were partly found within the confines of the substantia nigra, the nucleus reticularis superior and the lateral part of the nucleus reticularis medius and ventrolateral part of the nucleus reticularis inferior, respectively. No serotonergic cell bodies were found in the spinal cord. In the brain stem a dense serotonergic innervation was observed in all of the motor nuclei of the cranial nerves, in two layers of the tectum mesencephali, in the nucleus interpeduncularis pars ventralis, the nucleus profundus mesencephali pars rostralis, the periventricular grey, the nucleus parabrachialis, the vestibular nuclear complex, the nucleus descendens nervi trigemini, the nucleus raphes inferior, and parts of the nucleus tractus solitarii. Descending serotonergic pathways could be traced into the spinal cord via the dorsolateral, ventral and ventromedial funiculi, and were found to innervate mainly three parts of the spinal grey throughout the spinal cord, i.e. the dorsal part of the dorsal horn, the motoneuron area in the ventral horn, and the intermediate zone just lateral to the central canal. The results obtained in the present study suggest a close resemblance of the organization of the serotonergic system in reptiles and mammals, especially as to the serotonergic innervation of the spinal cord.

Descending pathways from the brain stem to the spinal cord in some reptiles. II. Course and site of termination

The course and termination of the pathways descending from the brain stem to the spinal cord have been studied by tracing the ensuing antero grade fiber degeneration, following appropriate lesions in the reptiles Testudo hermanni, Tupinambis nigropunctatus and Python reticulatus.

Desending pathways from the brain stem to the spinal cord in some reptiles. I. Origin

In the present study the origin of the pathways descending from the brain stem to the spinal cord has been investigated in the reptiles Testudo hermanni, Pseudemys scripta elegans, Tupinambis nigropunctatus and Python reticulatus. These reptiles, using highly different types of progression, have been selected, because fundamental variations in the organization of the central motor apparatus are to be expected.