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The data reviewed here demonstrate a capacity for neuronal plasticity in the aged human brain, even when affected by neurodegenerative disorders. However, given their location and environment, these morphological changes may have beneficial or deleterious consequences. In Parkinson disease, the changes observed in the substantia nigra are likely involved in compensatory mechanisms that may delay the appearance of the clinical symptoms, where as the synaptic plasticity in the striatum may aggravate the behavioral disturbances. Finally, it is likely that such synaptic plasticity requires a highly differentiated set of trophic molecules during the evolution of the pathological process. Further knowledge of these molecules is needed, however, before their use can be envisaged as possible therapeutic agents aimed at correcting the behavioral deficits owing to the disease.

A scale of relative affinities of a series of 2′-deoxycytidine and cytidine (CD) derivatives was established based on the data of cross-reactivities of these compounds as well as the displacements obtained from a competitive ELISA. No correlation could be established between the nucleosides modifying structures and the affinities. This can be explained by the possibilities of the modifying structures of intra- and intermolecular nonimmunospecific interactions owing to their degree of functionalization.

Cerebellar granule cells isolated from 7-d-old rats have been shown to die in vitro unless they are continuously exposed to elevated K+ (25 mM). Here we have characterized this neuronal death, and examined whether its major features are shared with those of sympathetic neurons following nerve growth factor (NGF) deprivation. Granule cells underwent active cell death accompanied by morphological features of apoptosis. Brain-derived neurotrophic factor (BDNF), but not NGF, was capable of preventing this neuronal death by acting posttranslationally. Moreover, semiquantitative RT-PCR, Northern blot, and immunoblot analyses showed thattrkB, the signal-transducing receptor for BDNF, was upregulated during neuronal death of granule cells in vitro. These results extend recent findings for the role of BDNF in granule cell development, and suggest that BDNF plays a pivotal role on the regulation of the neuronal death/survival of granule cells.

In the gracile axonal dystrophy (GAD) mutant mouse, the dyingback type axonal dystrophy of the primary afferent neurons in the gracile tract of the spinal cord was marked by severe gliosis characterized by the hypertrophy and proliferation of the fibrous astrocytes. Immunocytochemical observation for substance P (SP) revealed that SP-positive cells increased in the lesioned sites, primarily in the gracile nucleus of the medulla and subsequently in the gracile fasciculus of the spinal cord. The combined immunostaining of both SP and glial fibrillary acidic protein (GFAP) indicated that a strong correspondence exists between GFAP-positive networks and SP-positive grains, suggesting that SP was accumulated in the cytoplasm of astrocytes. The networks of SP-positive astrocytes spread all over the gracile tract and were densest at the subpial membrane. Similar lesions and SP activity were detected along the marginal zone of the lateral and ventral funiculi. Using an electron microscope, in addition to SP-positive axonal terminals in the gracile nucleus, most SP-positive cells in the gracile tract were identified as reactive astrocytes whose processes surrounded myelinated and nonmyelinated axons, and extended their foot processes to the blood vessels. Byin situ hybridization histochemistry of SP mRNA, we confirmed the synthesis of SP in the astrocytes. Although the functional significance of SP within astrocytes is not established here, these results imply that the astrocytes may play a role as a gliotransmitter through which the progress of axonal degeneration in the spinal cord was modified.

Localization of the α2 macroglobulin receptor (α2MR) was studied in postmortem human brain tissue of Alzheimer disease (AD) and age-matched control cases with a monoclonal antibody (A2MRα2) to the receptor. In control cases α2MR was detected in neurons, glia, and some capillaries. Neuronal staining was most conspicuous in the hippocampus and entorhinal cortex. In AD, α2MR immunoreactivity was enhanced. The staining intensity of some neurons was increased, as was the number of positive glial cells. In addition, senile plaques, tangles, and dystrophic neurites were strongly stained. These results suggest that α2MR is involved in AD pathology.