Cell loss and class distribution of TH-I cells in the substantia nigra of the neurological mutant, weaver

Smith, Morgan; Cooper, T.R.; Joh, Tong H.; Smith, David

doi:10.1016/0006-8993(90)91374-p

Cited by 20 publications

(7 citation statements)

References 17 publications

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“…Dopaminergic terminal density in the PD putamen (Fig. 3) was broadly in agreement with previous DAT,19, 28 tyrosine hydroxylase immunohistochemical studies,36, 37 and [ 3 H]mazindol receptor autoradiography studies,19, 38, 39 and confirms that loss is greatest in the sensorimotor territory whereas the spared region seems to correspond to the associative striatal territory 40…”

Section: Discussionsupporting

confidence: 90%

Dopaminergic innervation of the human striatum in Parkinson's disease

et al. 2005

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In Parkinson's disease (PD), dopaminergic input to the caudate nucleus and a band of putaminal tissue abutting the external globus pallidus seems well preserved on immunohistochemical staining for the dopamine transporter. Counting of dopaminergic terminals showed that terminal density in these regions in PD was the same as that in controls, which indicates that input is truly preserved and not a consequence of a compensatory upregulation of metabolism in a reduced pool of surviving terminals. When the branching pattern of dopaminergic axons coursing through the globus pallidus was examined, we found no evidence for increased axonal sprouting in PD that might have contributed to preservation of dopaminergic input to the putamen or caudate nucleus. Although terminal counting indicated that anatomic input was preserved to parts of the striatum, dopamine uptake site density in these regions was reduced significantly. This suggests that the impact of disease in these areas is more profound than was thought previously.

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Section: Discussionsupporting

confidence: 90%

Dopaminergic innervation of the human striatum in Parkinson's disease

et al. 2005

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“…Data reported earlier did not reveal a reduction in the number of TH-positive neurons in the midbrain of wv/+ mice (Roffler-Tarlov and Graybiel 1987;Roffler-Tarlov et al 1996;Triarhou et al 1988;Smith et al 1990). Taking into consideration the differences in the experimental design and a biological variability among individual wv/+ mice maintained on the B6CBA-Aw+J/A hybrid stock, the number of animals per group examined in previous studies may not have been sufficient to detect statistically significant differences.…”

Section: Discussionmentioning

confidence: 84%

“…Since the sizes of neuronal somata decrease with age in both wv/+ and +/+, the difference observed at P20 becomes less detectable and statistically nonsignificant in older animals. The reduction in the average size of cell bodies was characteristic for the residual TH-immunoreactive neurons in the SN of wv/wv mice (Smith et al 1990). In addition, the phenomenon of cell soma shrinkage with no obvious cell loss was detected in experimental conditions inducing slowly developing cellular atrophic changes of the nigral neurons (Lundberg et al 1994).…”

Section: Discussionmentioning

confidence: 96%

Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice

et al. 1997

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The phenotypic effect of the weaver mutation in the ventral midbrain of homozygous mutants is associated with the progressive loss of dopaminergic neurons. To discover whether the number of mesencephalic dopaminergic cells is altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA), and measured cross-sectional areas of neuronal somata in the SN of wv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in the wv/+ ventral midbrain was on average 13% lower than normal. Cell loss was detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles in the wv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses in the SN and VTA correlated with a 13.8% reduction in dopamine level in the ventral striatum in wv/+ mice at 14-16 months of age. Our findings imply that a single dose of the weaver gene in the mouse is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.

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“…Dopamine-containing cell groups of the midbrain Analysis of TH-positive neurons in the weaver midbrains suggested a close correspondence between the patterns of fiber loss in the striatum and the patterns of cell loss in the dopaminecontaining cell groups A8-A9-A10 (see also Gupta et al, 1987;Triarhou et al, 1988a;Smith et al, 1988). The marked loss of TH-positive nigral cells in the ventral tier of the substantia nigra pars compacta is almost certainly related to the striosomal defect in the mutants.…”

Section: Discussionmentioning

confidence: 91%

Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. I. Gradients and compartments

1990

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In mice carrying the autosomal recessive gene weaver, there is a massive postnatal loss of dopamine in the caudoputamen, the target of the nigrostriatal system, with relative (though not complete) preservation of dopamine in the ventral striatum, a target of the mesolimbic system. There is concomitant death of catecholaminergic neurons in the substantia nigra, with much less cell death in the limbic midbrain area. In the study reported here, we have reexamined the mesostriatal system of weaver mice by means of tyrosine hydroxylase (TH) immunohistochemistry in order to determine the local architecture of the defect within the striatum and substantia nigra. For the dorsal striatum, the most striking finding was the appearance in the weaver caudoputamen of small pockets of especially weak immunostaining within a larger dorsal zone of generally reduced TH-positive neuropil. These pockets were identified as striosomes by calbindin28k and met-enkephalin immunohistochemistry carried out on adjacent sections. In dorsal, central, and caudal sectors of the caudoputamen, there was also more generalized depletion of TH-immunoreactive neuropil. In the mid-brains of the mutants, the patterns of loss of TH-positive neurons appeared to correspond to these distributions of reduced immunostaining in the striatum. In the substantia nigra pars compacta, ventrally situated TH-positive neurons were especially affected, suggesting preferential depletion of TH-positive neurons projecting to striosomes. In addition, there was a central sector of nearly complete loss of TH-positive neurons in the substantia nigra para compacta and a marked depletion of TH-positive neurons in cell group A8 that, together, may have accounted for the diminution of TH-positive innervation of the striatal matrix. We conclude that the effects of the weaver gene discriminate among mesostriatal subsystems not only according to the regional affiliations of these subsystems within the dorsal and ventral striatum, but also according to the preferential association of the subsystems for the striosomal and matrical compartments of the caudoputamen. The depletion of TH-positive innervation was not confined to the dorsal striatum proper. The defect extended into the adjoining nucleus accumbens, where it appeared to affect the lateral "core" division, and included also a lateral part of the olfactory tubercle. Thus, as in the dorsal striatum, the defect in the TH-positive innervation of the ventral striatum closely follows the local architecture of this striatal region. Neuronal loss in the ventral tegmental area was not evident on qualitative analysis, but at the border between lateral cell group A 10 and medial cell group A9 there was obvious loss of immunostained neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Cell loss and class distribution of TH-I cells in the substantia nigra of the neurological mutant, weaver

Cited by 20 publications

References 17 publications

Dopaminergic innervation of the human striatum in Parkinson's disease

Dopaminergic innervation of the human striatum in Parkinson's disease

Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice

Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. I. Gradients and compartments

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