Biomedical subjects

K L Moya

Publications and source records attributed to K L Moya.

26 records · Page 2Linked to original sources

PubMed1990

Abnormal retinal projections alter GAP-43 patterns in the diencephalon.

In Syrian hamsters, mature retinal terminals contain only low levels of the growth-associated protein, GAP-43, whereas the lateral posterior nucleus (LP) of the thalamus contains high levels of this protein. Damage to the superior colliculus in neonatal hamsters induces retinal terminals to form dense patches of innervation in the LP, an area which otherwise receives little if any direct retinal input. The present study used GAP-43 antibodies to examine the interaction between abnormally routed optic fibers and the cells in the anomalous thalamic target zone. Immunohistochemistry revealed very little GAP-43 in the abnormal retinal projection to the LP, indicating that the normal developmental decline in GAP-43 levels occurs even in an inappropriate extracellular environment. Moreover, retinal fibers were found to exclude the protein from its normal territory, forming negatively-stained islands in those regions of the LP containing the retinal terminals. In order to identify the normal source of GAP-43-positive terminals in the LP, we surgically removed two major extrinsic afferents to this region, or we chemically eliminated local interneurons. Whereas removing projections from the SC or posterior cortex did not alter GAP-43 immunoreactivity in the LP, destruction of local interneurons with ibotenic acid resulted in markedly diminished levels of this protein. These results show that retinal terminals induced to form in an abnormal target area undergo their normal diminution of GAP-43, and that these retinal projections displace other GAP-43-rich terminals in the LP that appear to arise from local interneurons.

Animals↗

PubMed1990

Impaired verbal reasoning and constructional apraxia in subjects with right hemisphere damage.

In addition to causing visuospatial deficits, damage to the right cerebral hemisphere also impairs other cognitive abilities, including those requiring higher-order aspects of language. The present study used a standardized test battery to examine the relationship between visuospatial abilities and comprehension of narrative material in subjects having unilateral right hemisphere damage (RHD). In a series of 41 consecutively admitted RHD subjects, impairments in abstracting information from narrative passages were as prevalent and as severe in magnitude as constructional apraxia. Moreover, the extent of the visuospatial and linguistic impairments were highly correlated. Although age, educational levels, and degree of premorbid brain atrophy were all found to influence performance, analysis of a select subgroup of the population established that the covariation of visuospatial and verbal impairments is related to right hemisphere damage per se. Clinically, these findings may be of significance for understanding the pervasive cognitive impairments that are often evidenced by RHD patients.

Aged↗

PubMed1989

Immunohistochemical localization of GAP-43 in the developing hamster retinofugal pathway.

Metabolic labeling studies have shown that the developing hamster retinotectal pathway is marked by a high level of synthesis and axonal transport of the neuron-specific phosphoprotein GAP-43, which then decline sharply with synaptic maturation. To understand better the relationship of GAP-43 to specific developmental events, we used a monospecific antibody to examine the location of this protein in the optic tract and retinal target areas at various stages. In late embryonic and in neonatal hamsters, dense GAP-43 immunostaining was seen along the entire extent of the optic tract axons, including fascicles coursing over and through the lateral geniculate body (LGB) and within the upper layers of the superior colliculus (SC). The retinal origin of many of these fascicles was confirmed by their rapid disappearance after removal of the contralateral eye. During the first postnatal week, immunostaining in the fiber fascicles showed a marked decline, though the protein was still present throughout the neuropil of the LGB and SC. In the second postnatal week, the neuropil staining also diminished, and by 12 days after birth, both structures showed only light immunoreactivity. The high levels of GAP-43 in embryonic and neonatal optic tract axons coincide temporally with axon elongation, initial target contact, and collateral formation by the retinofugal fibers, whereas subsequent concentration of the protein in the neuropil suggests its involvement in the elaboration of terminal arbors and synaptogenesis.

Aging↗

PubMed1989

Peripheral nerve regeneration induces elevated expression of GAP-43 in the brainstem trigeminal complex of adult hamsters.

A polyclonal antibody was used to delineate the pattern of GAP-43 expression in central processes of trigeminal ganglion cells while their peripheral processes were undergoing regeneration. Two weeks after transection of the infraorbital nerve, levels of GAP-43 ipsilateral to the transection were greatly increased along the trajectory of infraorbital axons in the central trigeminal tract and also within the target neuropil. We conclude that elevated levels of GAP-43 in central processes of injured trigeminal ganglion cells occur in direct response to the regenerative response of the cell body and may have important implications for 'plasticity'-related changes seen in the adult trigeminal system.

Animals↗

PubMed1988

Changes in rapidly transported proteins in developing hamster retinofugal axons.

Proteins synthesized in retinal ganglion cells and conveyed to the terminals of optic tract axons in the rapid phase of axonal transport were analyzed at different developmental stages in the hamster. Animals between 2 d of age and adulthood were labeled intraocularly with 35S-methionine, and after a 4 hr survival time, the superior colliculus was dissected out, subjected to subcellular fractionation, and radiolabeled proteins in the particulate fraction analyzed by 2-dimensional gel electrophoresis and fluorography. The previously identified growth-associated phosphoprotein, GAP-43 (GAP-48, B-50, F1, pp46), was synthesized and transported at high levels in the neonate, but these levels declined precipitously after the second postnatal week. Immunohistochemical studies using a monospecific antibody showed that GAP-43 was localized along the entire length of retinal axons in the optic tract and target areas in P2 animals but was virtually absent in the adult visual pathway. By metabolic labeling, 2 proteins with molecular weights of about 230 kDa also showed a sharp decrease during development. In contrast, acidic proteins of 27 and 64 kDa, which were barely detectable in the neonate, increased steadily to become the most heavily labeled proteins of rapid axonal transport by the second postnatal week. Another group of proteins, of about 94-110 kDa, also rose to peak levels after birth but then declined. Temporal correlations between the molecular changes described here and the known anatomical events in optic tract development suggest that the synthesis and transport of particular membrane proteins may be directly related to the sequence of morphological changes.

Animals↗

PubMed1987

Enhanced visualization of axonally transported proteins in the immature CNS by suppression of systemic labeling.

In the neonate hamster, visualization of axonally transported proteins in the retinofugal pathway is obscured by high levels of systemic (background) labeling. Radiolabeled precursors injected into the eye diffuse rapidly into the general circulation and then across the immature blood-brain barrier to be incorporated into proteins that are synthesized throughout the brain. Systemic labeling can be suppressed, however, by i.p. injections of large amounts of either non-radioactive methionine 30 min after intraocular labeling with [35S]methionine, or non-radioactive leucine given at the time of intraocular labeling. Whereas the former competes with the radioactive precursor during incorporation into brain proteins (after most of the retinal labeling has already been achieved), the latter competes at the earlier stage of access to the brain. Both methods reduced background labeling by more than 60%, thereby allowing for unambiguous identification of axonally transported proteins. The pattern of rapidly transported proteins was found to be strikingly different between neonates and mature animals, including marked changes in an identified 'growth-associated protein' (50 kDa, pI 4.8).

Amino Acids↗

PubMed1986

Covariant defects in visuospatial abilities and recall of verbal narrative after right hemisphere stroke.

Eighteen patients with right hemisphere strokes and 10 age-matched normal controls were tested for visuospatial abilities and for recall of brief narrative passages. Visuospatial and verbal abilities were evaluated using an objective scoring protocol that quantified accuracy in reproducing individual details, appreciation of structural relationships, and the appearance of unwarranted intrusions. The right hemisphere damaged group was found to be impaired on all measures of verbal recall. Across subjects these defects, particularly the inability to abstract information from the narrative passages, correlated with the degree of constructional apraxia. Analysis of CT scans failed to define a discrete region of the right hemisphere selectively associated with either the visuospatial or verbal defects, but indicated that both are exacerbated by the presence of premorbid brain atrophy.

Aged↗

PubMed1985

Late changes in cerebral monoamine metabolism following focal ventrolateral cerebrocortical lesions in rats.

Twelve weeks after focal ventrolateral cerebrocortical suction lesions (ca. 12 X 4 mm) were made in rats, concentrations of the monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their metabolites were measured in several cortical and subcortical brain regions using high performance liquid chromatography with electrochemical detection. Widespread changes in the concentrations of monoamines, their metabolites, and metabolite:monoamine ratios were found in the hemisphere ipsilateral to unilateral (right) lesions, and bilaterally in animals with bilateral lesions. NE was decreased in undamaged dorsolateral cortex and hippocampus, and tended to be increased in striatum and midbrain ipsilateral to lesions. DA was increased in the hypothalamus of bilaterally lesioned animals, and also tended to be increased in striatum and midbrain. The changes of greatest magnitude and anatomical extent were found in the serotonin system: 5-HT was generally increased, and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA:5-HT ratio were decreased throughout the cerebral hemispheres ipsilateral to lesions. These widespread changes in cerebral 5-HT metabolism were qualitatively different and smaller than those previously found at 6 days after cortical lesions, and suggest a biphasic response of the ipsilateral 5-HT system to ventrolateral cortical injury.

3,4-Dihydroxyphenylacetic Acid↗