Forebrain Ischemia Triggers GABAergic System Degeneration in Substantia Nigra at Chronic Stages in Rats

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.

In vivo neural regeneration via AAV-NeuroD1 gene delivery to astrocytes in neonatal hypoxic-ischemic brain injury

“…We observed that in neonatal mice with HIBI, NeuroD1 predominantly converted astrocytes into GABAergic neurons. This is significant because GABAergic neurons are known to be severely damaged by HIBI [ 39 – 41 ], which can decrease the expression of the GABA synthase enzymes GAD65 and GAD67 in the hippocampus after neonatal HIBI [ 42 , 43 ]. The dysfunction and loss of GABAergic neurons can impair neural circuits and cognitive function [ 44 ].…”

In vivo neural regeneration via AAV-NeuroD1 gene delivery to astrocytes in neonatal hypoxic-ischemic brain injury

“…We observed that in neonatal mice with HIBI, NeuroD1 predominantly converted astrocytes into GABAergic neurons. This is significant because GABAergic neurons are known to be severely damaged by HIBI [ 39 – 41 ], which can decrease the expression of the GABA synthase enzymes GAD65 and GAD67 in the hippocampus after neonatal HIBI [ 42 , 43 ]. The dysfunction and loss of GABAergic neurons can impair neural circuits and cognitive function [ 44 ].…”

Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease

“…CAG repetition may cause muscle incoordination, muscle wasting, and skeletal muscle atrophy in HD patients [ 68 ]. Degeneration and lesion formation in rat cortical and striatal neurons delayed muscle movement and impaired coordination [ 69 ]. Chronic 3-NP injection promoted mitochondrial dysfunction, disrupting neurotransmitters that influence motor and muscular activity [ 21 , 70 ].…”

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction

“…[31] It has been explained in various studies that body weight get reduced in case of HD patients. [32] Moreover, slow motor movement symptoms are mainly present in the end stage of the HD patients. These bodyweight reduction and motor disturbances mimic the same dysfunction associated after 3-NP injected intoxicated rats.…”

In vivo neural regeneration via AAV-NeuroD1 gene delivery to astrocytes in neonatal hypoxic-ischemic brain injury

“…We observed that in neonatal mice with HIBI, NeuroD1 predominantly converted astrocytes into GABAergic neurons. This is significant because GABAergic neurons are known to be severely damaged by HIBI [ 39 – 41 ], which can decrease the expression of the GABA synthase enzymes GAD65 and GAD67 in the hippocampus after neonatal HIBI [ 42 , 43 ]. The dysfunction and loss of GABAergic neurons can impair neural circuits and cognitive function [ 44 ].…”

Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease

“…CAG repetition may cause muscle incoordination, muscle wasting, and skeletal muscle atrophy in HD patients [ 68 ]. Degeneration and lesion formation in rat cortical and striatal neurons delayed muscle movement and impaired coordination [ 69 ]. Chronic 3-NP injection promoted mitochondrial dysfunction, disrupting neurotransmitters that influence motor and muscular activity [ 21 , 70 ].…”

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction

“…[31] It has been explained in various studies that body weight get reduced in case of HD patients. [32] Moreover, slow motor movement symptoms are mainly present in the end stage of the HD patients. These bodyweight reduction and motor disturbances mimic the same dysfunction associated after 3-NP injected intoxicated rats.…”

In vivo neural regeneration via AAV-NeuroD1 gene delivery to astrocytes in neonatal hypoxic-ischemic brain injury

“…We observed that in neonatal mice with HIBI, NeuroD1 predominantly converted astrocytes into GABAergic neurons. This is significant because GABAergic neurons are known to be severely damaged by HIBI [ 39 – 41 ], which can decrease the expression of the GABA synthase enzymes GAD65 and GAD67 in the hippocampus after neonatal HIBI [ 42 , 43 ]. The dysfunction and loss of GABAergic neurons can impair neural circuits and cognitive function [ 44 ].…”

Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease

“…CAG repetition may cause muscle incoordination, muscle wasting, and skeletal muscle atrophy in HD patients [ 68 ]. Degeneration and lesion formation in rat cortical and striatal neurons delayed muscle movement and impaired coordination [ 69 ]. Chronic 3-NP injection promoted mitochondrial dysfunction, disrupting neurotransmitters that influence motor and muscular activity [ 21 , 70 ].…”

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction

“…[31] It has been explained in various studies that body weight get reduced in case of HD patients. [32] Moreover, slow motor movement symptoms are mainly present in the end stage of the HD patients. These bodyweight reduction and motor disturbances mimic the same dysfunction associated after 3-NP injected intoxicated rats.…”