Joseph T. Weber

Tumor Necrosis Factor-α: a Neuromodulator in the CNS

PAN, W., ZADINA, J.E., HARLAN, R.E., WEBER, J.T., BANKS, W.A. AND KASTIN, A.J. Tumor necrosis factor-α: a neuromodulator in the CNS. NEUROSCI BIOBEHAV REV 21(5) 603–613, 1997.—In the central nervous system (CNS), the cytokine tumor necrosis factor-α (TNFα) is produced by both neurons and glial cells, participates in developmental modeling, and is involved in many pathophysiological conditions. There are activity-dependent expressions of TNFα as well as low levels of secretion in the resting state. In contrast to the conventional view of a cytotoxic effect of TNFα, accumulating evidence suggests a beneficial effect when TNFα is applied at optimal doses and at specific periods of time. The bimodal effect is related to subtypes of receptors, activation of different signal transduction pathways, and the presence of other molecules that alter the intracellular response elements such as immediate-early genes. TNFα may be an important neuromodulator in development of the CNS, diseases of demyelination and degeneration, and in the process of regeneration. It could induce growth-promoting cytokines and neurotrophins, or it could increase the production of antiproliferative cytokines, nitric oxide, and free radicals, thereby contributing to apoptosis.

The neurotrophins and their receptors: Structure, function, and neuropathology

The neurotrophins are a family of polypeptides that promote differentiation and survival of select peripheral and central neurons. Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, and neurotrophin-5 are included in this group. In recent years, tremendous advances have been made in the study of these factors. This has stimulated our review of the field, characterizing the neurotrophins from initial isolation to molecular analysis. The review also discusses their synthesis, localization, and responsive tissues, in both the periphery and CNS. The complex receptor interactions of the neurotrophins are also analyzed, as are putative signal transduction mechanisms. Discussion of the observed and postulated involvement in neuropathological disorders leads to the conclusion that the neurotrophins are involved in the function and dysfunction of the nervous system.

A rapid myelin stain for frozen sections: modification of the Heidenhain procedure.

A protocol has been established for the staining of myelin in frozen sections. While the new method is relatively fast and simple, it eliminates the problems routinely encountered with myelin stains such as blotchiness and uneven staining. Modifications were introduced into the procedures in order to obtain excellent fiber staining results on a wide variety of tissue.

Pretectal complex and accessory optic system of primates.

In the present report, conflicting results regarding the pretectal complex and accessory optic system of primates are discussed. Subsequently data are presented and used in an attempt to clarify some of the issues. The retinal projections to the pretectal complex and accessory optic system of the tree shrew and squirrel monkey were examined using anterograde autoradiographic methods. These data demonstrate that, following intraocular injections of 3H-proline or 3H-fucose in the tree shrew, silver grains are apparent bilaterally over the pretectal olivary nucleus and the anterior and posterior pretectal nuclei and contralaterally over the nucleus of the optic tract. Following intraocular injections of the 3H-tracer in squirrel monkeys, dense transported label is observed bilaterally over the pretectal olivary nucleus and the nucleus of the optic tract with sparse label over the posterior and medial pretectal nuclei. In both the tree shrew and squirrel monkey, a differential retinal projection is observed, chiefly contralaterally, to all accessory optic terminal nuclei (i.e., the dorsal, lateral and medial terminal nuclei).

The opiate system in invertebrates

The presence in diverse species of a similar mode of communication, that of a soluble messenger binding to a receptor, raises the question as to whether the specific components of this system are equally widespread. Do invertebrates use the same hormones and receptors as vertebrates do? Invertebrates ranging from unicellular organisms to insects have been shown to contain opiate-like peptides and binding sites, and they exhibit biological responses to opiates. However, critical genetic data are lacking. It is not known how signal systems arise phylogenetically, but it is conceivable that signal molecules that are already present cause the formation of their own receptors from membrane proteins.

The demonstration of a retinal projection to the medial pretectal nucleus in the domestic cat and the squirrel monkey: an autoradiographic analysis

The anterograde autoradiographic tracing technique was used to demonstrate a projection from the retina to the medial pretectal nucleus in the domestic cat and the squirrel monkey. In the cat, the pathway terminates within the contralateral nucleus in two discrete loci. In the squirrel monkey, the retino-medial pretectal pathway is bilateral and terminates in a single locus.

Synaptic connections of central carotid sinus afferents in the nucleus of the tractus solitarius of the rat. I. An electron microscopic study.

SummaryA transganglionic transport technique was used to study the synaptic connections of the central carotid sinus afferents in the nucleus of the tractus solitarius of the rat by electron microscopy. The caudal part of the nucleus was profusely innervated. Labelled fibres extended to the contralateral nucleus, and to the ipsilateral dorsal motor nucleus of the vagus nerve, nucleus ambiguus, spinal nucleus of the trigeminal nerve and the area postrema. The labelled terminals were densely packed with clear, predominantly spherical vesicles about 50 nm in diameter and a few often swollen mitochondria. The terminals synapsed on dendrites of various calibres, spindle- or pear-shaped somal profiles with short axes lesser than 8 μm, and axon terminals. In axo-axonal synapses, most labelled terminals appeared to be presynaptic. Frequently, profiles of labelled terminals were in direct apposition with one another. The latter may represent the morphological substrate of the interaction between baro- and chemoreceptor inputs in the nucleus of the tractus solitarius and warrants further study. The present results indicate that in addition to direct inputs, the carotid sinus afferents are able to influence second-order neurons in the nucleus of the tractus solitarius indirectly through presynaptic modulation.

Subcortical connections of area 17 in the tree shrew: an autoradiographic analysis

The present anterograde autoradiographic study reveals several targets of the striate cortex (area 17) of the tree shrew which were not previously observed in studies which used anterograde degeneration methods; our data also confirm several previous findings. The results are discussed in the context of these projections modulating ascending visual information (claustrum, lateral intermediate nucleus, pulvinar, dorsal lateral geniculate, cells of the external medullary lamina, reticular nucleus of the thalamus, superficial collicular layers, and the anterior and posterior pretectal nuclei) or visuomotor information (putamen, caudate, ventral lateral geniculate, pontine gray, and the anterior and posterior pretectal nuclei).

The pretectal complex of the cat: cells of origin of projections to the pulvinar nucleus

The pretectal projection to the pulvinar nucleus in the cat was examined using the retrograde transport of wheat germ agglutinin-horseradish peroxidase. These data show that both visual and non-visual areas of the pretectal complex contribute to the projection. Specifically, large numbers of labeled neurons are located within the pretectal olivary nucleus with a substantial number of labeled neurons observed within the nucleus of the optic tract. Labeled neurons are also located within the medial, anterior and posterior nuclei, but not to the degree observed in the other pretectal nuclei. Morphometric analysis of labeled and Nissl-stained neurons indicate that the pretectopulvinar pathway is not correlated to any single cell size.

Interhemispheric and subcortical collaterals of single cortical neurons in the adult cat

The results of this study demonstrate the existence of single neocortical neurons that send axon collaterals into the corpus callosum, to terminate within the contralateral hemisphere, and subcortically, to terminate within the ipsilateral superior colliculus.