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At least 1,153 records · Page 64Linked to original sources
PubMed1979

Axonal transport of nucleosides, nucleotides and 4S RNA in the neonatal rat visual system.

The axonal migration of RNA, the nucleoside uridine and its nucleotide derivates (NS/NT) were compared in neonatal and young adult rat optic axons. Tritiated uridine was injected into right eyes of developing (1- or 4-day-old) and young adult (40-day-old) rats which were sacrificed at times after injection ranging from 6 h to 20 days. Right and left lateral geniculates were removed and assayed for trichloroacetic acid soluble (NS/NT) and RNA radioactivity. Left minus right geniculate (L-RLG) radioactivity was used as an index of axonally migrating radioactivity. Results showed that uridine and its phosphorylated derivatives were transported along both neonatal and young adult rat optic axons. Greater than 90% of right geniculate (blood-borne) TCA soluble radioactivity was metabolized to volatile substances (probably 3H2O) by three days after injection, leaving approximately 3% of the neonatal and approximately 10% of the adult activity as [3H]NS/NT. In left geniculate fractions (containing transported material) approximately 15% and 40% of total TCA soluble radioactivity was present as [3H]NS/NT in neonates and adults, respectively. Thus, axonal NS/NT appears to be relatively protected from degradation when compared with blood-borne NS/NT. The amount of L-RLG [3H]RNA in the neonates was 10 times higher than in young adults. Peaks of neonatal [3H]RNA occurred at 5 and 10 days after birth, whether injections were made at 1 or 4 days of age indicating that this [3H]RNA may be linked to developmental events. Gel electrophoretic analysis of neonatal geniculate RNA indicated that a small portion of the [3H]RNA in the first peak represented axonally transported 4S RNA. The remainder of the L-RLG [3H]RNA in the neonates was probably due to a rapid and efficient incorporation of axonally transported [3H]NS/NT into extraaxonal geniculate RNA. In contrast, little or no axonal RNA transport could be demonstrated in the young adults.

Age Factors↗
PubMed1997

Differential regulation of fast axonally transported proteins during the early response of rat retinal ganglion cells to axotomy.

We have found that the early response of axotomized rat retinal ganglion cells is characterized by the differential regulation of a number of fast axonally transported proteins. The abundance of 23 radiolabeled fast transported proteins was analyzed at 2 and 5 days after axotomy using two-dimensional gel electrophoresis. Corresponding changes in retinal GAP-43 mRNA were measured using northern analysis. Within 2 days of injury, > 40% of the transported proteins analyzed, including GAP-43, showed increased labeling above control levels. Approximately 13% of transported proteins decreased below control levels, whereas the remainder did not change. Five days after axotomy, only GAP-43 and another fast transported protein, C3, continued to sustain measurable increased labeling above control levels; all previously elevated proteins appeared to have been down-regulated by this time, which corresponds to the onset of cell death. These differential changes were accompanied by parallel increases in GAP-43 mRNA. These results suggest that the molecular changes within rat retinal ganglion cells are differentially regulated within two stages subsequent to damage, initial regenerative growth followed by cell death.

Animals↗
PubMed1991

Axonal transport of cadmium in the olfactory nerve of the pike.

109Cd2+ was applied in the olfactory chambers of pikes (Esox lucius) and the dynamics of the axoplasmic flow of the metal was determined in the olfactory nerves by gamma spectrometry and autoradiography. The results showed that the 109Cd2+ is transported at a constant rate along the olfactory nerves. The profile of the 109Cd2+ in the nerves showed a wave front of transported metal followed by a saddle region. When the nasal chambers were washed 2 hr after application of the 109Cd2+ well-defined transport peaks for the metal were seen in the olfactory axons. The maximal velocity for the transport of 109Cd2+, which corresponds to the movement of the wave front, was 2.38 +/- 0.10 mm/hr (mean +/- S.E.) at the experimental temperature (10 degrees C). The average velocity for the transport of the 109Cd2+, which corresponds to the peak apex movement of the wave, was 2.18 +/- 0.05 mm/hr (mean +/- S.E.) at 10 degrees C. The transported 109Cd2+ was strongly accumulated in the anterior parts of the olfactory bulbs, whereas in other brain areas the levels of the metal remained low. Autoradiography of a pike exposed to 109Cd2+ via the water showed a strong labelling in the receptor-cell-containing olfactory rosettes, whereas other structures in the olfactory chambers were only weakly labelled. The accumulation and axonal transport in the olfactory neurons may be noxious and constitute an important component in the toxicology of cadmium in fish, and this may apply also to some other heavy metals.

Animals↗
PubMed1986

[Projections of the neurons of the medial terminal nucleus of the accessory optic tract to the caudate nucleus of the cat detected by the combined methods of retrograde axonal transport and experimental degeneration].

Projections of neurons of the medial terminal nucleus of the accessory optic tract receiving direct retinal inputs to the head and body of caudate nucleus are shown in cat by the retrograde axonal transport of horseradish peroxidase and experimental degeneration. These projections are mainly ipsilateral and uniformly distributed in the above mentioned parts of the nucleus. The neurons of the medial terminal nucleus establishing synaptic connections with caudate neurons have different shapes and sizes (from 20 X 10 microns to 37.5 X 18 microns) and are located both in the ventral and dorsal parts of the nucleus. Conclusions are made about functional significance of these projections in the regulation of the muscular tension.

Animals↗
PubMed1995

Experimental diabetic neuropathy. Inhibition of protein mono-ADP-ribosylation prevents reduction of substance P axonal transport.

The extranuclear endogenous mono-ADP-ribosylation of proteins in cellular fractions from retinas of control and diabetic rats was studied. At least six proteins were ADP-ribosylated in the crude extract, membrane and cytosolic fractions from control preparations, whereas in diabetic rats the number of labeled proteins and the extent of labeling were highly reduced. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations of the extent of ADP-ribosylation of the 38 K cytosolic, 39 K, 40 K membrane and 39 K, 41 K and 42 K crude extract proteins. These data suggest a hyperactivity of extranuclear endogenous protein mono-ADP-ribosylation in the diabetic rat retina, and that treatment with silybin inhibits such enzyme activity, thus improving the extent of ADP-ribosylation. Sciatic nerve axonal transport of substance P was reduced markedly in diabetic rats, and inhibition of mono-ADP-ribosylation with silybin prevented such a loss in spite of high blood glucose levels. These results suggest that the abnormal endogenous ADP-ribosylation of proteins might play a role in the onset of diabetic peripheral neuropathy and its inhibition may represent a novel pharmacological approach to the treatment of diabetes complications.

Adenosine Diphosphate Ribose↗
PubMed2002

Neurotropism and retrograde axonal transport of a canine adenoviral vector: a tool for targeting key structures undergoing neurodegenerative processes.

Viral tropism refers to the ability of a virus to selectively infect a given subset of cells. It relies on a variety of viral and host determinants that entail virus binding and entry into target cells, in addition to the presence of genetic elements that allow or enhance viral gene expression in a specific manner. Here we report the results of neuroanatomical studies in rat brains injected in different cerebral structures with vectors derived from the canine adenovirus type 2 (CAV2), whose natural target is the respiratory epithelium. Control animals injected with vectors derived from the human adenovirus type 5 (Ad5) displayed the previously documented pattern of gene transfer into both neurons and glial cells. Injection of CAV2 vectors resulted in selective transduction of neuronal cells. Cy3-labeled CAV2 particles allowed us to establish the high affinity of this vector for neuronal processes in vitro and their rapid uptake and retrograde axonal transport in vivo. After intrahippocampal injections, labeled particles were found, within 1 hour, closely associated to the nuclei of the neurons in layer II of the entorhinal cortex. Injections into the striatum resulted in a massive transduction of dopaminergic neurons in the substantia nigra compacta. The high efficiency with which CAV2 vectors are retrogradely transported opens the possibility of targeting a transgene to neuron populations remote from the injection site and difficult to access. Our data support the possibility to target key structures undergoing a degenerative process: the enthorhinal cortex, which is affected first in Alzheimer's disease; and the substantia nigra compacta, which undergoes degeneration in Parkinson's disease.

Adenoviridae↗
PubMed1988

Reduced axonal transport of the G4 molecular form of acetylcholinesterase in the rat sciatic nerve during aging.

Aging in the sciatic nerve of the rat is characterized by various alterations, mainly cytoskeletal impairment, the presence of residual bodies and glycogen deposits, and axonal dystrophies. These alterations could form a mechanical blockade in the axoplasm and disturb the axoplasmic transports. However, morphometric studies on the fiber distribution indicate that the increase of the axoplasmic compartment during aging could obviate this mechanical blockade. Analysis of the axoplasmic transport, using acetylcholinesterase (AChE) molecular forms as markers, demonstrates a reduction in the total AChE flow rate, which is entirely accounted for by a significant bidirectional 40-60% decrease in the rapid axonal transport of the G4 molecular form. However, the slow axoplasmic flow of G1 + G2 forms, as well as the rapid transport of the A12 form of AChE, remain unchanged. Our results support the hypothesis that the alterations observed in aged nerves might be related either to the impairment in the rapid transport of specific factor(s) or to modified exchanges between rapidly transported and stationary material along the nerves, rather than to a general defect in the axonal transport mechanisms themselves.

Acetylcholinesterase↗
PubMed2002

Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.

Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS. We disrupted the Fgf14 gene and introduced an Fgf14(N-beta-Gal) allele that abolished Fgf14 expression and generated a fusion protein (FGF14N-beta-gal) containing the first exon of FGF14 and beta-galactosidase. Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. Neuropharmacological studies showed that Fgf14-deficient mice have reduced responses to dopamine agonists. The paroxysmal hyperkinetic movement disorder phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen. Strikingly, the FGF14N-beta-gal chimeric protein was efficiently transported into neuronal processes in the basal ganglia and cerebellum. Together, these studies identify a novel function for FGF14 in neuronal signaling and implicate FGF14 in axonal trafficking and synaptosomal function.

Animals↗
PubMed1985

Projections of medial terminal accessory optic nucleus, ventral tegmental nuclei, and substantia nigra of rabbit and rat as studied by retrograde axonal transport of horseradish peroxidase.

Projections of the medial terminal nucleus (MTN) of the accessory optic system, the ventral tegmental area of Tsai, and the substantia nigra of the rabbit and the rat have been studied by the method of retrograde axonal transport of horseradish peroxidase. The data show that MTN projections are remarkably similar in the rabbit and rat. The MTN projects heavily to the ipsilateral nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system and to a portion of the contralateral ventral tegmental area of Tsai that we have termed the visual tegmental relay zone (VTRZ). Further, the MTN sends projections to the ipsilateral mesencephalic (deep mesencephalic nucleus, pars medialis) and pontine (nucleus reticularis pontis oralis) reticular formations; the contralateral dorsolateral division of the basal pontine complex; the superior and lateral vestibular nuclei (contralateral in rat; bilateral in rabbit); and the ipsi- and contralateral interstitial nucleus of Cajal, nucleus of Darkschewitsch, and supraoculomotor-periaqueductal gray. The findings also indicate that the MTN has a small bilateral, but mainly ipsilateral, projection to the dorsal cap, its ventrolateral outgrowth, and the B division of the inferior olivary complex. This study further reveals that ventral tegmental nuclei (n. parabrachialis pigmentosus and n. paranigralis) and subdivisions of the substantia nigra (pars compacta and pars reticulata) project to many brain stem targets of the MTN. Thus, the VTRZ projections are similar to those of the MTN in both distribution and density except that the VTRZ projection to the inferior olive is substantially stronger. The nucleus parabrachialis pigmentosus sends a small contralateral projection to the VTRZ and a moderate-sized bilateral projection to the supraoculomotor-periaqueductal gray. The nucleus paranigralis sends a moderate number of axons to the ipsilateral deep mesencephalic nucleus, pars medialis, and the nucleus reticularis pontis oralis and provides a strong bilateral projection to the supraoculomotor-periaqueductal gray. The pars compacta of the substantia nigra provides a sparse input to the ipsilateral deep mesencephalic nucleus, pars medialis, and nucleus reticularis pontis oralis, and to the contralateral VTRZ and sends a moderate number of axons, bilaterally, to the supraoculomotor-periaqueductal gray. The pars reticulata of the substantia nigra sends an ipsiateral projection of moderate size to the intermediate and deep layers of the superior colliculus, sparse ipsilateral projections to the deep mesencephalic nucleus, pars medialis, and nucleus reticularis pontis oralis, and a sparse bilateral projection to

Animals↗