Is There a Role of Nogo-A in the Nigrostriatal System?

2012 ◽  
Vol 73 (S 03) ◽  
Author(s):  
L. Andereggen ◽  
K. Schawkat ◽  
S. Di Santo ◽  
R. Andres ◽  
M. Reinert ◽  
...  
Keyword(s):  
Nigrostriatal System

scholarly journals The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Victor Blokhin ◽  
Maria Shupik ◽  
Ulyana Gutner ◽  
Ekaterina Pavlova ◽  
Albert T. Lebedev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sphingolipid Metabolism ◽  
Nigrostriatal System ◽  
Dopaminergic Cell ◽  
Metabolism Enzymes ◽  
Clinical Stages ◽  
Sphingosine 1 Phosphate

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

scholarly journals Critical role of Nitric Oxide on Nicotine-Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in Rats

2010 ◽  
Vol 16 (3) ◽  
pp. 127-136 ◽  
Author(s):  
Vincenzo Di Matteo ◽  
Massimo Pierucci ◽  
Arcangelo Benigno ◽  
Ennio Esposito ◽  
Giuseppe Crescimanno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Role ◽  
Nigrostriatal System

Evidence for a role of endogenous opioids in the nigrostriatal system: Influence of naloxone and morphine on nigrostriatal dopaminergic supersensitivity

1983 ◽  
Vol 270 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Ira D. Hirschhorn ◽  
Daniel Hittner ◽  
Eliot L. Gardner ◽  
Joseph Cubells ◽  
Maynard H. Makman
Keyword(s):  
Endogenous Opioids ◽  
Nigrostriatal System ◽  
Dopaminergic Supersensitivity

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

2018 ◽  
Author(s):  
Tatiana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

2018 ◽  
Author(s):  
Tatiana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease

2022 ◽  
Vol 23 (1) ◽  
pp. 528
Author(s):  
Beatriz Pardo ◽  
Eduardo Herrada-Soler ◽  
Jorgina Satrústegui ◽  
Laura Contreras ◽  
Araceli del Arco
Keyword(s):  
Direct Consequence ◽  
Epileptic Encephalopathy ◽  
Brain Cell ◽  
Nigrostriatal System ◽  
Current Evidence ◽  
Mice Model ◽  
Cellular Mechanisms ◽  
Brain Functions ◽  
Neuronal Functions

AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named “early infantile epileptic encephalopathy 39” (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4779 ◽  
Author(s):  
Tatiana V. Tarasova ◽  
Olga A. Lytkina ◽  
Valeria V. Goloborshcheva ◽  
Larisa N. Skuratovskaya ◽  
Alexandr I. Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson’s disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in a brain with PD, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra but not the ventral tegmental area in mouse brain

2018 ◽  
Author(s):  
Tatyana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

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