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D Goldowitz

Publications and source records attributed to D Goldowitz.

At least 73 records · Page 4Linked to original sources
PubMed1986

Proto-oncogene c-myc is expressed in cerebellar neurons at different developmental stages.

During post-natal cerebellar development the steady-state levels of c-myc transcripts exhibit characteristic changes. As determined by the S1 nuclease protection assay the level of c-myc transcript, which is very high in the late embryonic cerebellum, decreased to low levels shortly after birth. One week later there is a second period of c-myc mRNA accumulation followed by a marked decline to finally reach the low adult value. The second peak of high c-myc mRNA level correlates well with the proliferation of granule cell precursors, and it is characterized by a marked change in the ratio of the two types of transcripts started at the known c-myc promoters 1 and 2. This indicates a change in the cell population involved in the transcription of the c-myc gene. In situ hybridization shows transiently elevated c-myc mRNA levels in neurons of the cerebellar cortex. At post-natal days 3 and 10 (P3 and P10) c-myc transcripts are detectable in the superficial external granular layer composed primarily of mitotically active (neural precursor) cells. Purkinje cell somata show cytoplasmic label at P10. These large postmitotic neurons undergo rapid differentiation at this developmental stage. In the adult cerebellum the low c-myc mRNA level is apparently due to Purkinje cells with barely detectable amounts of c-myc transcripts. The vast majority of mature cerebellar neurons, the internal granule cells, have no specific hybridization signal for c-myc. We conclude that neurons in vivo can accumulate c-myc messenger during proliferation and/or differentiation, perhaps as a cellular response to an external signal.

Aging↗
PubMed1986

Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks.

The objectives of the present study are to assess the import of gene-imposed structural alterations on behavioral performance and obtain performance data preliminary to studies of experimental mouse chimera behavior. Reeler, staggerer, and weaver neurological mutant, and control B6C3 and ichthyosis mice were tested on radial arm maze and active avoidance tasks. Weaver mice had incapacitating seizures while performing the radial arm maze task and were, therefore, removed from further testing. Staggerer mice displayed a significant deficit on both tasks compared to control mice. Homozygous reeler mice (rl/rl) also had a significant deficit on the active avoidance task compared to +/rl control mice but not significantly poorer than ichthyosis mice. However, their performance on the radial arm maze task, while initially poor, improved so that they performed the task similar to wild-type controls. Three of the reeler mice reached criterion for solving the radial arm maze task. None of the staggerer mice reached criterion. These data are discussed in terms of the value of using neurologically mutant mice in dissecting structural-functional relationships. It is suggested that the behavior of these mutants might point toward specific components of cerebellar involvement in behavioral acts.

Animals↗
PubMed1985

Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, "wasted".

Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants. The wst/wst mice do not survive past 30 days of age. The present report describes histologic and functional abnormalities in a longitudinal analysis (17 to 29 days postpartum) of wst/wst mice. In addition to a marked age-dependent decline in wst/wst body weight as well as spleen and thymus wet weight to body weight ratios, we have observed a significant decline in spleen and thymus cell number in these organs, compared with phenotypically normal (+/+ or +/wst) littermates. Histologic analysis of the wst/wst thymus revealed marked cortical pyknosis at 23 days of age and significant cortical depletion by 26 days postpartum. The wst/wst spleen at 23 days of age and later was characterized by a marked reduction in the content of red pulp. Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates. The wst/wst spleen LPS responsiveness was also markedly altered in an age-dependent fashion. Hypotheses are presented concerning the possible site(s) of gene action in the wst/wst mutant which may mediate the observed morphologic and functional abnormalities.

Age Factors↗
PubMed1984

Regulation of axonal ingrowth into area dentata as studied by sequential, double intraocular brain tissue transplantation.

The anterior eye chamber was used as a model environment to study, in isolation, the interaction of embryonic area dentata transplants with transplants of one of three important sources of in situ innervation: entorhinal cortex, locus coeruleus or septal nuclei. None of these brain regions significantly affected the morphogenesis or in oculo growth of area dentata transplants. All three brain regions innervated the area dentata transplant. Entorhinal cortical transplants sent nerve fibers into a limited, and apparently specific, region of area dentata that was adjacent to the entorhinal transplant. This light innervation contrasts to the predominant innervation of area dentata by entorhinal cortex in situ. The fluorescent, noradrenergic neurons of locus coeruleus provided the area dentata transplant with an abundance of fine varicose nerve fibers. Given about 100 noradrenergic neurons in the locus coeruleus transplant and 4 to 6 months joint survival, the area dentata transplant was noradrenergically hyperinnervated. The cholinergic neurons of the septal nuclei transplant had a prolific ingrowth of acetylcholinesterase (AChE)-positive nerve fibers to the area dentata transplant. There appeared to be a mutual exclusion between the extrinsic AChE-positive fibers and the intrinsic Timm's-positive granule cell mossy fibers in the area dentata transplant. We conclude that isolated replicas of the coeruleo-, septo-, and entorhinal cortico-dentate pathways can be made through sequential intraocular double grafting. The nature of the in oculo connectivity between these replicates offers clues as to the mechanisms that might account for the regulation of nerve growth.

Animals↗
PubMed1984

Degree of hyperinnervation of area dentata by locus coeruleus in the presence of septum or entorhinal cortex as studied by sequential intraocular triple transplantation.

In situ area dentata receives a sparse noradrenergic innervation from locus coeruleus. Embryonic area dentata co-transplanted with locus coeruleus to the anterior eye chamber receives an abundant ingrowth of nerves from the noradrenergic neurons of the locus graft. We sought to identify restrictive forces acting on coeruleo-dentate axons by arranging for the innervation of area dentata transplants by either entorhinal cortex or septal nuclei transplants prior to locus coeruleus transplantation. The noradrenergic hyperinnervation was not inhibited when locus coeruleus transplants were placed on the opposite side of area dentata from the entorhinal or septal transplant. Noradrenergic innervation of area dentata was restricted when the locus coeruleus transplant was placed in contact with the septal transplant. This inhibitory interaction seemed to take place between the septal and locus coeruleus transplants rather than in the area dentata neuropil. This type of interaction points towards one means by which axonal growth may be inhibited during development or in the adult.

Animals↗
PubMed1983

The neurological mutation staggerer is expressed in embryonic cerebellar transplants matured in the anterior eye chamber of normal mice.

Transplantation of embryonic day 11 cerebellar anlage to the anterior eye chamber of wildtype recipient mice was used to investigate the intrinsic character of the cerebellar mutation staggerer. One phenotypic expression of the staggerer gene in vivo is a postnatal degeneration of cerebellar granule cells. After 43 days of in oculo development cerebellar buds from homozygous staggerer embryos similarly develop into nervous tissues lacking granule cells. On the other hand, transplants of wildtype cerebellar anlagen contain a large population of granule cells. Both the staggerer and wildtype cerebellar transplants had a survival of large neurons, characteristic of Purkinje, Golgi and deep nuclei cells.

Animals↗
PubMed1982

Immunohistochemical demonstration of plasticity in GABA neurons of the adult rat dentate gyrus.

The distribution of GABA fibers within the dentate gyrus was immunohistochemically examined following lesions of the entorhinal cortex in the adult rat. A major change in the pattern of the GAD immunoreactive fibers within the molecular layer, characterized by a marked increase in the density of fibers in the outer molecular layer, was observed. This change in the lamination of the dentate GABA fibers following entorhinal lesions appeared very similar to the changes which occur in acetylcholinesterase staining following entorhinal denervation of the dentate. These results provide morphological support for the sprouting of GABA fibers in the dentate gyrus in response to perforant path destruction.

Acetylcholinesterase↗
PubMed1982

Granule cell as a site of gene action in the weaver mouse cerebellum: evidence from heterozygous mutant chimeras.

Experimental mouse chimeras were used to determine the site(s) of gene action in the weaver mutant cerebellum. Chimeras containing mixtures of heterozygous weaver (wv/+) and non-weaver (+/+) cells were produced by the standard embryo aggregation technique. The non-weaver component of the chimera was chosen so that Purkinje cells or granule cells could be distinguished histologically from weaver Purkinje or granule cells. Levels of beta-glucuronidase activity were used to mark Purkinje cells, with the weaver strain having a high beta-glucuronidase activity, while the non-weaver strain had low beta-glucuronidase activity. The increased centralized clumping of heterochromatin in ichthyosis (ic) mutant mice compared to non-ic mice was used to mark granule cell populations. In the weaver chimera, there was a decreased cerebellar size, decreased numbers of Purkinje and granule cells, and increased ectopic Purkinje and granule cells compared to non-weaver, control mice. With the glucuronidase cell marker, it was found that there was no correlation between ectopia and genotype; that is, genetically normal cells, as well as weaver cells, were found in ectopic positions. Thus, the weaver gene acts extrinsic to the Purkinje cells in creating the ectopia characteristic of heterozygous weaver mutants. Analysis of the ectopic granule cells, however, revealed that 100% of the ectopic granule cells were from the weaver component of the chimera. Thus, the weaver gene intrinsically affects granule cells in causing ectopia. Other hypothetical sites of gene action would produce a genetically mixed population of ectopic granule cells, which was not the case in this study. These findings are discussed in relation to other abnormalities in the heterozygous weaver mutant and in regard to the Bergmann glia and homozygous mutant. Finally, speculations on the nature of the granule cell deficit are discussed briefly.

Animals↗
PubMed1980

Do neurotrophic interactions control synapse formation in the adult rat brain?

The role of axonal transport in the regulation of synaptic contacts was studied in the adult rat dentate gyrus. Colchicine was applied to the fimbria, which includes fibers of the hippocampal commisural system, and axonal transport was measured. Axonal transport in these and other fibers of the fimbria was markedly reduced. The region of commissural termination in the molecular layer of the dentate gyrus was monitored by electron microscopy for changes in the number of synapses per unit area following cholchicine treatment, sodium chloride treatment, or fimbrial transection. Four days after colchicine treatment there was no change in the number of synapses. However, at 11 and 60-70 days after colchicine treatment the number of synapses per unit area significantly increased. This increase occurred throughout the commissural terminal zone, but it did not occur in terminal zones of other afferents in the dentate gyrus. The increased synaptic density appeared to arise from the commissural system itself because removal of commissural fibers eliminates the increase (in addition to the normal commissural input). These findings suggest a role for axonally transported trophic substances in the specific regulation of synaptogenesis in the dentate gyrus of the adult rat.

Acetylcholinesterase↗
PubMed1979

The specificity of reactive synaptogenesis: a comparative study in the adult rat hippocampal formation.

The CA1 region of the hippocampus in the mature rat is shown to possess the capacity to form new synapses following a lesion of either the commissural afferents, which removes 41% of the synaptic input to stratum radiatum, or commissural and associational afferents, which destroys 74% of the synaptic input. With both types of lesion, extensive reinnervation occurs without obvious changes in lamination of afferent fibers and without accompanying changes in the acetylcholinesterase-(AChE) staining pattern. This is in contrast to what is known to occur in the hippocampal dentate gyrus following an ipsilateral entorhinal lesion where afferent lamination is reordered and where AChE-staining intensifies. A comparison between the disparate patterns of reinnervation in these closely related structures affords the opportunity to examine some of the specific factors that may regulate synaptic readjustments in brain.

Acetylcholinesterase↗
PubMed1976

Electrophysiological analysis of the projection from the contralateral entorhinal cortex to the dentate gyrus in normal rats.

The projection from the contralateral entorhinal cortex to the dentate gyrus is shown to exert a monosynaptic excitatory action. Stimulation of the contralateral entorhinal cortex evokes unitary granule cell discharges in the dentate gyrus. This evoked activity is followed by a period of inhibition lasting about 50 msec. Laminar analyses of field potentials generated by contralateral medial entorhinal stimulation localize the synaptic activity to the middle portion of the granule cell dendrites. This localization is consistent with the termination site of the contralateral entorhinal projection as previously shown anatomically. Earlier studies have indicated that the entorhinal cortex excites only the ipsilateral dentate gyrus. These findings now demonstrate that the cortical input to the dentate gyrus is bilateral in normal rats. However, the contralateral projection appears to be much less efficacious than the ipsilateral input.

Animals↗