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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

Coronal sections of the ventral mesencephalon showing GAD67-immunoreactivity (GAD-ir) in substantia nigra (SN) at day 56 after 12.5 minutes of global ischemia. The dense GAD-ir is in SN. (a) GAD-ir fiber network is especially prominent in substantia nigra par reticulata (SNR), pars compata (SNC), and pars lateralis (SNL) in sham rats. (b) higher magnification of boxed area in (a). The processes and the cell body are encircled by GAD67+ puncta. GAD-ir puncta are closely apposed to GAD-ir dendrites and outline a cell body. Note the GAD67+ puncta in contact with the soma and proximal dendrites leaving the cell body. (c)–(f) distribution of GAD-ir from 4 different ischemia rats. (g)-(h) Higher magnification of boxed areas in (c) and (f), respectively. As compare, to sham rats, ischemic rats showed an evident reduction of GAD-ir in SN: the number and density of GAD-puncta are decreased. (b), (g), and (h) are counterstained by hematoxylin.
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fig4: Coronal sections of the ventral mesencephalon showing GAD67-immunoreactivity (GAD-ir) in substantia nigra (SN) at day 56 after 12.5 minutes of global ischemia. The dense GAD-ir is in SN. (a) GAD-ir fiber network is especially prominent in substantia nigra par reticulata (SNR), pars compata (SNC), and pars lateralis (SNL) in sham rats. (b) higher magnification of boxed area in (a). The processes and the cell body are encircled by GAD67+ puncta. GAD-ir puncta are closely apposed to GAD-ir dendrites and outline a cell body. Note the GAD67+ puncta in contact with the soma and proximal dendrites leaving the cell body. (c)–(f) distribution of GAD-ir from 4 different ischemia rats. (g)-(h) Higher magnification of boxed areas in (c) and (f), respectively. As compare, to sham rats, ischemic rats showed an evident reduction of GAD-ir in SN: the number and density of GAD-puncta are decreased. (b), (g), and (h) are counterstained by hematoxylin.

Mentions: Intense GAD67 immunoreactivity (GAD67-ir) was present in the substantia nigra (SN) (Figure 4). The dense and long GAD67 fibers formed a network, which was especially concentrated in SNR and to a lesser extent in SNL and SNC in all of the sham (Figures 4(a) and 4(b)) and ischemic rats (Figures 4(c)–4(h)). At higher magnification, labeled profiles typically contained numerous small clear vesicles. Dense punctate patches of immunoreactivity were observed throughout SN. GAD67-ir was visualized mainly in neuronal processes: axon and dendrites and the puncta were closely apposed to the processes. The processes of GAD67-ir neurons were long and formed a fibrous network within the SNR (Figure 4(b)).


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)

Coronal sections of the ventral mesencephalon showing GAD67-immunoreactivity (GAD-ir) in substantia nigra (SN) at day 56 after 12.5 minutes of global ischemia. The dense GAD-ir is in SN. (a) GAD-ir fiber network is especially prominent in substantia nigra par reticulata (SNR), pars compata (SNC), and pars lateralis (SNL) in sham rats. (b) higher magnification of boxed area in (a). The processes and the cell body are encircled by GAD67+ puncta. GAD-ir puncta are closely apposed to GAD-ir dendrites and outline a cell body. Note the GAD67+ puncta in contact with the soma and proximal dendrites leaving the cell body. (c)–(f) distribution of GAD-ir from 4 different ischemia rats. (g)-(h) Higher magnification of boxed areas in (c) and (f), respectively. As compare, to sham rats, ischemic rats showed an evident reduction of GAD-ir in SN: the number and density of GAD-puncta are decreased. (b), (g), and (h) are counterstained by hematoxylin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2957857&req=5

fig4: Coronal sections of the ventral mesencephalon showing GAD67-immunoreactivity (GAD-ir) in substantia nigra (SN) at day 56 after 12.5 minutes of global ischemia. The dense GAD-ir is in SN. (a) GAD-ir fiber network is especially prominent in substantia nigra par reticulata (SNR), pars compata (SNC), and pars lateralis (SNL) in sham rats. (b) higher magnification of boxed area in (a). The processes and the cell body are encircled by GAD67+ puncta. GAD-ir puncta are closely apposed to GAD-ir dendrites and outline a cell body. Note the GAD67+ puncta in contact with the soma and proximal dendrites leaving the cell body. (c)–(f) distribution of GAD-ir from 4 different ischemia rats. (g)-(h) Higher magnification of boxed areas in (c) and (f), respectively. As compare, to sham rats, ischemic rats showed an evident reduction of GAD-ir in SN: the number and density of GAD-puncta are decreased. (b), (g), and (h) are counterstained by hematoxylin.
Mentions: Intense GAD67 immunoreactivity (GAD67-ir) was present in the substantia nigra (SN) (Figure 4). The dense and long GAD67 fibers formed a network, which was especially concentrated in SNR and to a lesser extent in SNL and SNC in all of the sham (Figures 4(a) and 4(b)) and ischemic rats (Figures 4(c)–4(h)). At higher magnification, labeled profiles typically contained numerous small clear vesicles. Dense punctate patches of immunoreactivity were observed throughout SN. GAD67-ir was visualized mainly in neuronal processes: axon and dendrites and the puncta were closely apposed to the processes. The processes of GAD67-ir neurons were long and formed a fibrous network within the SNR (Figure 4(b)).

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