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Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats.

Lin B, Levy S, Raval AP, Perez-Pinzon MA, Defazio RA - Cardiovasc Psychiatry Neurol (2010)

Bottom Line: At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased.CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01).Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.

ABSTRACT
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

No MeSH data available.


Related in: MedlinePlus

VGAT immunolabeling in SN in coronal midbrain section of rats after 12.5 minutes of global ischemia at day 56. (a) VGAT-ir in sham rat. (b) Higher magnification of boxed area in (a). The insertion with hematoxylin counterstaining presents a higher magnification of VGAT-ir. Immunohistochemical analysis shows abundant puncta of VGAT-positive dots, and some of these puncta encircle an unlabeled neuron's body and its dendrites. (c)–(g): VGAT-ir in 5 ischemic rats at day 56 after injury. (h): higher magnification of boxed area in (g) shows lower density and less amount of VGAT puncta and fiber network than sham rat.
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fig6: VGAT immunolabeling in SN in coronal midbrain section of rats after 12.5 minutes of global ischemia at day 56. (a) VGAT-ir in sham rat. (b) Higher magnification of boxed area in (a). The insertion with hematoxylin counterstaining presents a higher magnification of VGAT-ir. Immunohistochemical analysis shows abundant puncta of VGAT-positive dots, and some of these puncta encircle an unlabeled neuron's body and its dendrites. (c)–(g): VGAT-ir in 5 ischemic rats at day 56 after injury. (h): higher magnification of boxed area in (g) shows lower density and less amount of VGAT puncta and fiber network than sham rat.

Mentions: VGAT is reported to selectively identify GABAergic nerve terminals [29]. Immunohistochemical analysis showed numerous VGAT immunopositive puncta in SN from sham animals (Figures 3, 6(a), and 6(b)). Intensive punctuate immunostaining was present in the processes of neurons including axon and dendrites, and the long processes formed a fiber network. Intense VGAT-immunoreactivity (VGAT-ir) was observed in the SNR, SNL, and SNC (Figure 6). VGAT-ir was more intense and uniform in SN in sham rats (Figure 6(a)). At higher magnification, VGAT-ir was primarily detected in small processes but was absent in cell bodies; the puncta encircled neuronal soma (Figure 6(b)). Ischemia appeared to decrease VGAT expression in SN. Ischemic rats showed less puncta and an apparent lower density of VGAT-ir (Figures 6(c)–6(h)). Although VGAT-immunoreactivity appeared significantly less intense in postischemic rats, no significant quantitative differences in gross optical density were observed owing to the high degree of variability in the intensity of immunoreactivity even within the sham group (data not shown).


Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats.

Lin B, Levy S, Raval AP, Perez-Pinzon MA, Defazio RA - Cardiovasc Psychiatry Neurol (2010)

VGAT immunolabeling in SN in coronal midbrain section of rats after 12.5 minutes of global ischemia at day 56. (a) VGAT-ir in sham rat. (b) Higher magnification of boxed area in (a). The insertion with hematoxylin counterstaining presents a higher magnification of VGAT-ir. Immunohistochemical analysis shows abundant puncta of VGAT-positive dots, and some of these puncta encircle an unlabeled neuron's body and its dendrites. (c)–(g): VGAT-ir in 5 ischemic rats at day 56 after injury. (h): higher magnification of boxed area in (g) shows lower density and less amount of VGAT puncta and fiber network than sham rat.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: VGAT immunolabeling in SN in coronal midbrain section of rats after 12.5 minutes of global ischemia at day 56. (a) VGAT-ir in sham rat. (b) Higher magnification of boxed area in (a). The insertion with hematoxylin counterstaining presents a higher magnification of VGAT-ir. Immunohistochemical analysis shows abundant puncta of VGAT-positive dots, and some of these puncta encircle an unlabeled neuron's body and its dendrites. (c)–(g): VGAT-ir in 5 ischemic rats at day 56 after injury. (h): higher magnification of boxed area in (g) shows lower density and less amount of VGAT puncta and fiber network than sham rat.
Mentions: VGAT is reported to selectively identify GABAergic nerve terminals [29]. Immunohistochemical analysis showed numerous VGAT immunopositive puncta in SN from sham animals (Figures 3, 6(a), and 6(b)). Intensive punctuate immunostaining was present in the processes of neurons including axon and dendrites, and the long processes formed a fiber network. Intense VGAT-immunoreactivity (VGAT-ir) was observed in the SNR, SNL, and SNC (Figure 6). VGAT-ir was more intense and uniform in SN in sham rats (Figure 6(a)). At higher magnification, VGAT-ir was primarily detected in small processes but was absent in cell bodies; the puncta encircled neuronal soma (Figure 6(b)). Ischemia appeared to decrease VGAT expression in SN. Ischemic rats showed less puncta and an apparent lower density of VGAT-ir (Figures 6(c)–6(h)). Although VGAT-immunoreactivity appeared significantly less intense in postischemic rats, no significant quantitative differences in gross optical density were observed owing to the high degree of variability in the intensity of immunoreactivity even within the sham group (data not shown).

Bottom Line: At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased.CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01).Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.

ABSTRACT
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

No MeSH data available.


Related in: MedlinePlus