Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K

Yamada, Tatsuo; McGeer, Patrick L.; Baimbridge, K.G.; McGeer, Edith G.

doi:10.1016/0006-8993(90)91236-a

Cited by 416 publications

(269 citation statements)

References 12 publications

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“…Yet remarkably few (7.7%) co-localized calbindin-D28kD . Hence this subpopulation closely corresponds to the dopaminergic neurons thought to be most directly and strongly affected by Parkinson disease lesions (Yamada et al, 1990). These findings also clearly corroborate another key point we have already stressed in previous reports Renda et al, 1997).…”

Section: Discussionsupporting

confidence: 89%

“…Because these neurons are also immunonegative for Calbindin D28kD they are considered the dopaminergic neuron subpopulation most directly involved in Parkinson disease lesions (Yamada et al, 1990). The distribution patterns of their immunopositive terminals corresponds to a part of the nigrostriatal, mesolimbic, mesocortical and mesothalamic pathways normally projecting from these mesencephalic areas.The same antiserum was also used to study the distribution patterns of immunoreactive cells during the first three weeks after birth in rat brain (Nonomura et al, 1994), during the brain ontogeny in rat embryos (Park et al, 2000), and in various other apparatus Fujimiya et al, 1994;Sunday et al, 2001).…”

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confidence: 99%

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Fate of (D-Ala2)-deltorphin-I-like immunoreactive neurons in 6-hydroxydopamine lesioned rat brain

Casini¹,

Pinna²,

Tooyama³

et al. 2009

Eur J Histochem

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The use of a polyclonal antiserum specific to C-terminal tetrapeptide amide of (D-Ala 2 )deltorphin-I, a naturally occurring amphibian skin opioid peptide, has already demonstrated the presence of immunoreactive neurons in rat midbrain. Double immunostaining identified these neurons as a subpopulation of the mesencephalic dopaminergic neurons that were also tyrosine hydroxylase-immunopositive and calbindin-D28kD-negative, namely, the neurons predominantly affected in Parkinson disease. We followed the fate of these neurons after a monolateral injection of 6-hydroxy-dopamine into rat brain. Almost all the immunopositive neurons and their nigrostriatal, mesolimbic and mesocortical projections on the side ipsilateral to the lesion disappeared. Only a few scattered immunopositive neurons within the substantia nigra, pars compacta, and those of supramammillary nucleus remained unaffected. The consistent overlap of dopamine and this new molecule provides a further key to identifying the mammalian counterpart of these amphibian skin opioid peptides.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Fate of (D-Ala2)-deltorphin-I-like immunoreactive neurons in 6-hydroxydopamine lesioned rat brain

Casini¹,

Pinna²,

Tooyama³

et al. 2009

Eur J Histochem

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“…2i and data not shown). The calbindin-D 28K -expressing DA neurons, which are relatively spared in Parkinson's disease 24 , were also reduced, by 57% and 42% in the SNpc and VTA of Hipk2 −/− mutants at P28, respectively (Fig. 2e,f, j).…”

Section: Resultsmentioning

confidence: 93%

Essential function of HIPK2 in TGFβ-dependent survival of midbrain dopamine neurons

et al. 2006

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Transforming growth factor beta (TGFβ) is a potent trophic factor for midbrain dopamine (DA) neurons, but its in vivo function and signaling mechanisms are not entirely understood. We show that the transcriptional cofactor homeodomain interacting protein kinase 2 (HIPK2) is required for the TGFβ-mediated survival of mouse DA neurons. The targeted deletion of Hipk2 has no deleterious effect on the neurogenesis of DA neurons, but leads to a selective loss of these neurons that is due to increased apoptosis during programmed cell death. As a consequence, Hipk2 −/− mutants show an array of psychomotor abnormalities. The function of HIPK2 depends on its interaction with receptor-regulated Smads to activate TGFβ target genes. In support of this notion, DA neurons from Hipk2 −/− mutants fail to survive in the presence of TGFβ3 and Tgfβ3 −/− mutants show DA neuron abnormalities similar to those seen in Hipk2 −/− mutants. These data underscore the importance of the TGFβ-Smad-HIPK2 pathway in the survival of DA neurons and its potential as a therapeutic target for promoting DA neuron survival during neurodegeneration.Ventral midbrain DA neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) control extrapyramidal movement and a variety of cognitive

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“…Whereas the highest percentage of caspase-3-positive neurons was observed in the lateroventral part of the structure (68.4%), where neuronal loss is most severe in PD [91% according to Fearnley and Lees (25)], it is higher in the dorsal part of the SNpc (47.2%) than in the ventromedial part (30.4%), where neuronal loss is 56% and 71%, respectively. This apparent discrepancy may be due either to differences in delineation of the SNpc subregions or to the presence of additional factors in one of these subregions (28). Of course, these speculative arguments leave the possibility open that, within the SNpc, the distribution of caspase-3 does not contribute to regional vulnerability.…”

Section: Caspase-3 May Be a Vulnerability Factor For Pigmented Da Neumentioning

confidence: 99%

Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease

Hartmann

Hunot

Michel

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

645

379

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Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3 immunohistochemistry on the postmortem human brain, we observed a positive correlation between the degree of neuronal loss in dopaminergic (DA) cell groups affected in the mesencephalon of PD patients and the percentage of caspase-3-positive neurons in these cell groups in control subjects and a significant decrease of caspase-3-positive pigmented neurons in the substantia nigra pars compacta of PD patients compared with controls that also could be observed in an animal model of PD. This suggests that neurons expressing caspase-3 are more sensitive to the pathological process than those that do not express the protein. In addition, using an antibody raised against activated caspase-3, the percentage of active caspase-3-positive neurons among DA neurons was significantly higher in PD patients than in controls. Finally, electron microscopy analysis in the human brain and in vitro data suggest that caspase-3 activation precedes and is not a consequence of apoptotic cell death in PD.T he pathological hallmarks of Parkinson's disease (PD) are a loss of dopaminergic (DA) neurons in the mesencephalon and the presence of Lewy bodies in altered neurons. The exact cause of this neuronal loss is still unknown, but recent human postmortem studies have suggested that, in PD, nigral DA neurons die by apoptosis (1-3) as do DA neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (4,5), an in vivo model of PD. However, the significance of purely morphological human postmortem features suggestive of apoptosis remained controversial, and the results of investigations into molecular apoptotic markers in PD brains are awaited to confirm the morphologic studies (6).Extensive in vitro studies in nonneuronal and neuronal cell systems indicate that aspartate-specific cysteine proteases (caspases) are effectors of apoptosis (7). In neurons, several lines of evidence indicate that caspase-3 (CPP32͞Yama͞Apopain), a 32-kDa cytosolic protein, plays a major role in the executive phase of apoptosis (8, 9). First, cerebral hyperplasia and cellular disorganization are observed in caspase-3-deficient mice (10). Second, neuronal death in experimental models of several acute and chronic neurodegenerative disorders has been associated with activation of caspase-3 (11-13). Third, with special reference to PD, neurotoxins commonly used to induce experimental parkinsonian syndromes, e.g., 1-methyl-4-phenylpyridinium (MPP ϩ ) and 6-hydroxydopamine (6-OHDA), have been shown to exert their proapoptotic actions via activation of caspase-3-like proteases in neuronal in vitro models (14-16). To date, however, cellular expression of caspase-3 has not been studied in postmortem brain from patients with PD or any other neurologic disorders. In the present study, we thus analyzed caspase-3 distribution and activation in PD and experimental models of the dise...

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Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K

Cited by 416 publications

References 12 publications

Fate of (D-Ala2)-deltorphin-I-like immunoreactive neurons in 6-hydroxydopamine lesioned rat brain

Fate of (D-Ala2)-deltorphin-I-like immunoreactive neurons in 6-hydroxydopamine lesioned rat brain

Essential function of HIPK2 in TGFβ-dependent survival of midbrain dopamine neurons

Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease

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