Medial forebrain bundle axotomy during development induces apoptosis in dopamine neurons of the substantia nigra and activation of caspases in their degenerating axons

2002 ◽  
Vol 452 (1) ◽  
pp. 65-79 ◽  
Author(s):  
Bassem F. El-Khodor ◽  
Robert E. Burke
Keyword(s):  
Substantia Nigra ◽  
Medial Forebrain Bundle ◽  
Dopamine Neurons ◽  
Degenerating Axons

Increased Mitochondrial DNA Deletions in Substantia Nigra Dopamine Neurons of the Aged Rat

2015 ◽  
Vol 7 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Gemma M. Parkinson ◽  
Christopher V. Dayas ◽  
Doug W. Smith
Keyword(s):  
Mitochondrial Dna ◽  
Substantia Nigra ◽  
Dopamine Neurons ◽  
Aged Rat ◽  
Dna Deletions

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

scholarly journals Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease

2021 ◽  
Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Clinical Symptoms ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Resonance Imaging ◽  
Mean Values

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

scholarly journals Adeno-Associated Viral Delivery of GDNF Promotes Recovery of Dopaminergic Phenotype following a Unilateral 6-Hydroxydopamine Lesion

2002 ◽  
Vol 11 (3) ◽  
pp. 215-227 ◽  
Author(s):  
John Mcgrath ◽  
Elishia Lintz ◽  
Barry J. Hoffer ◽  
Greg A. Gerhardt ◽  
E. Matthew Quintero ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Viral Vectors ◽  
Medial Forebrain Bundle ◽  
Therapeutic Potential ◽  
Clinical Situation ◽  
Dopamine Neurons ◽  
Nigrostriatal System ◽  
Nigrostriatal Pathway ◽  
Neurotoxic Lesion ◽  
6 Hydroxydopamine

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopamine neurons that has been proposed for use in the treatment of Parkinson's disease (PD). Previous studies using viral vectors to deliver GDNF in rodent models of PD have entailed administering the virus either prior to or immediately after neurotoxin-induced lesions, when the nigrostriatal pathway is largely intact, a paradigm that does not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, recombinant adeno-associated virus carrying the gene encoding GDNF (rAAV-GDNF) was administered to animals bearing a maximal lesion in the nigrostriatal system, more closely resembling fully developed PD. Rats were treated with 6-hydroxydopamine into the medial forebrain bundle and assessed by apomorphine-induced rotational behavior for 5 weeks prior to virus administration. Within 4 weeks of a single intrastriatal injection of rAAV-GDNF, unilaterally lesioned animals exhibited significant behavioral recovery, which correlated with increased expression of dopaminergic markers in the substantia nigra, the medial forebrain bundle, and the striatum. Our findings demonstrate that rAAV-GDNF is capable of rescuing adult dopaminergic neurons from near complete phenotypic loss following a neurotoxic lesion, effectively restoring a functional dopaminergic pathway and diminishing motoric deficits. These data provide further support for the therapeutic potential of rAAV-GDNF-based gene therapy in the treatment of PD.

scholarly journals Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunlong Zhang ◽  
Feng Tan ◽  
Pingyi Xu ◽  
Shaogang Qu
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acid ◽  
Animal Models ◽  
Substantia Nigra ◽  
Excitatory Amino Acid ◽  
Synaptic Cleft ◽  
Dopamine Neurons ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
And Function

Parkinson’s disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.

scholarly journals AMP kinase regulates ligand-gated K-ATP channels in substantia nigra dopamine neurons

Neuroscience ◽  
2016 ◽  
Vol 330 ◽  
pp. 219-228 ◽  
Author(s):  
Ke-Zhong Shen ◽  
Yan-Na Wu ◽  
Adam C. Munhall ◽  
Steven W. Johnson
Keyword(s):  
Substantia Nigra ◽  
Dopamine Neurons ◽  
Amp Kinase

The Evolving Understanding of Dopamine Neurons in the Substantia Nigra and Ventral Tegmental Area

2018 ◽  
Vol 80 (1) ◽  
pp. 219-241 ◽  
Author(s):  
Stephanie C. Gantz ◽  
Christopher P. Ford ◽  
Hitoshi Morikawa ◽  
John T. Williams
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Ventral Tegmental

scholarly journals Effect of various extracts of Tabernaemontana divaricata on haloperidol induced catalepsy in rats

2014 ◽  
Vol 3 (3) ◽  
pp. 240-242 ◽  
Author(s):  
Chanchal N. Raj ◽  
A. Balasubramaniam ◽  
Sayyed Nadeem
Keyword(s):  
Animal Model ◽  
Substantia Nigra ◽  
Neurodegenerative Diseases ◽  
Pharmaceutical Journal ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Selective Loss ◽  
Tabernaemontana Divaricata ◽  
Medicinal Use ◽  
Different Doses

Parkinson’s disease (PD) is one of the neurodegenerative diseases with selective loss of dopamine neurons of the substantia nigra pars compacta. In the present study, anti-cataleptic activity of Tabernaemontana divaricata leaves extracts viz. aqueous and ethanolic at different doses (50, 100 and 150 mg/kg i.p.) were studied using haloperidol (1 mg/kg, i.p.) induced catalepsy in rats which is a useful animal model for screening drugs for Parkinson’s disease. Both the extracts were found to reduce catalepsy significantly (P<0.001) as compared to the haloperidol treated rats showing greater effect at 150 mg/kg i.p. dose. Thus the present study reveals the anti-cataleptic activity of Tabernaemontana divaricata evaluating the traditional folklore medicinal use of the plant.DOI: http://dx.doi.org/10.3329/icpj.v3i3.17891 International Current Pharmaceutical Journal, February 2014, 3(3): 240-242

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