Developmental Neuroscience

Varon, Silvio; Manthorpe, Marston; Williams, Lawrence R.

doi: 10.1159/000112334pmid: 6088207

Neuronal maintenance and neuritic growth during development are increasingly recognized as being under the extrinsic control of neuronotrophic- and neurite-promoting agents. Protein agents ('factors') are the most studied but not the only molecules exerting such controls. It appears increasingly likely that adult neurons in situ are equally subject to similar extrinsic regulations. Two recently studied in vivo models for peripheral and central neural regeneration have demonstrated trauma-related accumulations of neuronotrophic-and neurite-promoting factors in the adult rat, in close temporal correlation with neuronal maintenance and axonal regrowth, respectively. Deficits in the supply or utilization of similar factors may underlie neuronal or glial regressive processes in aging, and in selected neuronal diseases such as Parkinson, ALS and Alzheimer. Speculative approaches to, and potential problems of, clinical interventions addressing putative neuronotrophic deficits are discussed.

Varon, Silvio; Manthorpe, Marston; Williams, Lawrence R.

doi: 10.1159/000112335pmid: N/A

Neuronal maintenance and neuritic growth during development are increasingly recognized as being under the extrinsic control of neuronotrophic- and neurite-promoting agents. Protein agents ('factors') are the most studied but not the only molecules exerting such controls. It appears increasingly likely that adult neurons in situ are equally subject to similar extrinsic regulations. Two recently studied in vivo models for peripheral and central neural regeneration have demonstrated trauma-related accumulations of neuronotrophic-and neurite-promoting factors in the adult rat, in close temporal correlation with neuronal maintenance and axonal regrowth, respectively. Deficits in the supply or utilization of similar factors may underlie neuronal or glial regressive processes in aging, and in selected neuronal diseases such as Parkinson, ALS and Alzheimer. Speculative approaches to, and potential problems of, clinical interventions addressing putative neuronotrophic deficits are discussed.

Mikoshiba, Katsuhiko; Terada, Soichiro; Takamatsu, Ken; Shimai, Kazuyo; Tsukada, Yasuzo

doi: 10.1159/000112336pmid: 6205843

The organization of the fiber connections and architecture of the cerebellum of reeler mutant mice was analyzed by an immunohistochemical and histochemical procedure. By immunohistochemical staining of the myelinated fiber arborization with antiserum against myelin basic protein, it was found in the reeler cerebellum that the fibers ran in all directions throughout the white matter. Some of the fibers surrounded Purkinje cells. The distribution of AChE-positive fibers was abnormal and some Purkinje cells surrounded by AChE-positive fibers were present. Molecular layers and glomeruli showed strong succinic dehydrogenase (SDH) activity. The white matter of the reeler cerebellum showed a mosaic of SDH-positive and -negative sites. The results indicate that changes in the distribution of myelinated fiber arborization and the change in the distribution of SDH and AChE activity are different in each part of the cerebellum as a result of the disorganization of the architecture of the reeler mutation.

Hajeri-Germond, M.; Trojan, J.; Uriel, J.; Hauw, J.J.

doi: 10.1159/000112337pmid: 6205844

Exogenous chicken α-Fetoprotein (AFP) was added to embryonic chick dorsal root ganglia plated on gelatin-coated tissue culture dishes at different stages during the differentiation process and its intracellular uptake demonstrated by immunocytochemical methods. Other embryonic serum proteins were added as a control. Morphologically well-differentiated neurons (ganglion cells) appeared positively labeled for AFP, contrasting with weakly stained other cell types: these included spindle-shaped cells identified as Schwann cells and larger, often closely packed cells, which could be less mature neurons. Fibroblasts were found negative or faintly stained. No AFP was noticeable in cultures grown in the absence of the protein. These results suggest that the presence of AFP in the developing CNS is for the most part, if not entirely, due to protein uptake as opposed to in situ synthesis.

Ginalski-Winkelmann, Helga; Omlin, François X.; Matthieu, Jean-Marie

doi: 10.1159/000112338pmid: 6205845

Myelination was studied between 15 and 135 days postnatally in peripheral nerves of myelin deficient (mld) mice and in unaffected littermates. The nerve weights were not affected by the mutation and showed a 4-fold increase during the developmental period studied. The amounts of myelin present in peripheral nerves, as shown by biochemical and morphological techniques, were slightly reduced in mld in comparison to control mice. In controls, the concentration of myelin doubled during the investigation period. The increase of myelin basic protein (MBP) in total nerve homogenate paralleled the deposition of myelin, but the MBP concentration remained constant in normal myelin. In contrast, in mld myelin MBP concentrations were extremely low until 60 days of age and increased thereafter to reach almost normal values at 135 days. Similarly, the amounts of myelin isolated at 85 and 135 days were normal. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP; EC 3.1.4.37), the myelin-specific enzyme, showed normal specific activities in mld nerves. In mld and control myelin, CNP-specific activities decreased during development suggesting a preferential localization of CNP in Schwann cell plasma membranes. In contrast to the central nervous system, other myelin proteins were not altered in mld peripheral nervous system (PNS) and the very low MBP content had no severe repercussions on the composition and structure of the myelin sheath. Furthermore, Schwann cells appeared normal in mld PNS. Nevertheless, more subtle alterations could be detected. Slightly decreased amounts of myelin were observed in young mld mice and preliminary results indicate discrete alterations of the myelin periodicity. After 60 days postnatally, when the repressed MBP synthesis was removed, MBP was incorporated into the myelin sheath and the MBP deficit was nearly corrected.

Karpiak, Stephen E.; Vilim, Ferdinand; Mahadik, S.P.

doi: 10.1159/000112339pmid: 6678760

Several studies have shown that exogenous gangliosides can stimulate neurite outgrowth (in vitro), accelerate peripheral nerve regeneration (in vivo) and facilitate CNS recovery after lesioning. Experiments were designed to assess the effects of ganglioside administration, on neonatal development. Rat neonates received daily subcutaneous injections of gangliosides from PN day 5 through 15. Learning behavior (acquisition and retention) was facilitated in rats which had received injections of either total, GM1 or GD1b ganglioside. Rats injected with GD1a and GT1b ganglioside were not different from controls. Levels of total AChE activity as well as its 4s and 10s molecular forms in cortex, were assayed at PN days 9, 14, 21 and 28 in rats injected with GM1 ganglioside. These animals had consistently higher levels of enzyme activity as compared to saline controls. It is hypothesized that exogenous gangliosides accelerate CNS maturation.

doi: 10.1159/000112340pmid: N/A