Limits...
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

CR-ir neurons are decreased 4–8 weeks after 12.5 minutes of global ischemia (mean ± SD). The bar graph shows the numbers of CR-neurons in the entire SN at level 5.3 mm posterior to bregma are markedly reduced at days 28 and 56 (*indicates the significant difference compared to sham, day 3 and day 7; p < .01, ANOVA, post hoc Tukey HSD). No other significant differences were detected.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2957857&req=5

fig8: CR-ir neurons are decreased 4–8 weeks after 12.5 minutes of global ischemia (mean ± SD). The bar graph shows the numbers of CR-neurons in the entire SN at level 5.3 mm posterior to bregma are markedly reduced at days 28 and 56 (*indicates the significant difference compared to sham, day 3 and day 7; p < .01, ANOVA, post hoc Tukey HSD). No other significant differences were detected.

Mentions: Calretinin (CR) has been used to detect a subpopulation of GABAergic interneurons [30]. In our study, calretinin-like immunoreactivity was detected in the midbrain at all time points after ischemia. Within the SN, calretinin was exclusively observed in cell bodies and short dendritic processes (Figure 7). In normal rats, CR-immunopositive neurons were densely distributed in SNC, especially in the ventral tier, and many CR-neurons were seen in SN pars lateralis (SNL), which formed a diagonal band-like zone (Figure 7(a)). Several CR-neurons were observed in SNR. During days 3–56 following ischemia, the numbers of CR-neurons progressively declined. The numbers of CR-positive neurons in the entire SNC were 156 ± 23 in sham group (n = 3); 144 ± 15 at day 3 (n = 5); 128 ± 24 at day 7 (n = 6); 95 ± 12 at day 28 (n = 6), and 100 ± 16 at day 56 (n = 7). Decrease of CR-ir neurons was detected from day 28 through day 56: a 27% decrease from day 3 to day 56 (ANOVA, p < .01), a 26% decrease from day 7 to day 28 (p = .01), and a 18% decrease from day 7 to day 56 (p < .05) was observed. No significant differences were detected between the day 3 and day 7 or between days 3–7 and sham (p > .05) (see Figure 8). These data demonstrate a delayed loss of CR-ir beginning after day 7.


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)

CR-ir neurons are decreased 4–8 weeks after 12.5 minutes of global ischemia (mean ± SD). The bar graph shows the numbers of CR-neurons in the entire SN at level 5.3 mm posterior to bregma are markedly reduced at days 28 and 56 (*indicates the significant difference compared to sham, day 3 and day 7; p < .01, ANOVA, post hoc Tukey HSD). No other significant differences were detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957857&req=5

fig8: CR-ir neurons are decreased 4–8 weeks after 12.5 minutes of global ischemia (mean ± SD). The bar graph shows the numbers of CR-neurons in the entire SN at level 5.3 mm posterior to bregma are markedly reduced at days 28 and 56 (*indicates the significant difference compared to sham, day 3 and day 7; p < .01, ANOVA, post hoc Tukey HSD). No other significant differences were detected.
Mentions: Calretinin (CR) has been used to detect a subpopulation of GABAergic interneurons [30]. In our study, calretinin-like immunoreactivity was detected in the midbrain at all time points after ischemia. Within the SN, calretinin was exclusively observed in cell bodies and short dendritic processes (Figure 7). In normal rats, CR-immunopositive neurons were densely distributed in SNC, especially in the ventral tier, and many CR-neurons were seen in SN pars lateralis (SNL), which formed a diagonal band-like zone (Figure 7(a)). Several CR-neurons were observed in SNR. During days 3–56 following ischemia, the numbers of CR-neurons progressively declined. The numbers of CR-positive neurons in the entire SNC were 156 ± 23 in sham group (n = 3); 144 ± 15 at day 3 (n = 5); 128 ± 24 at day 7 (n = 6); 95 ± 12 at day 28 (n = 6), and 100 ± 16 at day 56 (n = 7). Decrease of CR-ir neurons was detected from day 28 through day 56: a 27% decrease from day 3 to day 56 (ANOVA, p < .01), a 26% decrease from day 7 to day 28 (p = .01), and a 18% decrease from day 7 to day 56 (p < .05) was observed. No significant differences were detected between the day 3 and day 7 or between days 3–7 and sham (p > .05) (see Figure 8). These data demonstrate a delayed loss of CR-ir beginning after day 7.

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