Biochemical alteration in cerebrospinal fluid precedes behavioral deficits in Parkinsonian rats induced by 6-hydroxydopamine

2009 ◽  
Vol 72 ◽  
pp. S55-S65 ◽  
Author(s):  
Jia-Wei Lin ◽  
Chwen-Ming Shih ◽  
Yen-Chou Chen ◽  
Chien-Min Lin ◽  
Jo-Ting Tsai ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Behavioral Deficits ◽  
Biochemical Alteration ◽  
6 Hydroxydopamine

scholarly journals Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease

2015 ◽  
Vol 112 (28) ◽  
pp. 8756-8761 ◽  
Author(s):  
Chun-Hyung Kim ◽  
Baek-Soo Han ◽  
Jisook Moon ◽  
Deog-Joong Kim ◽  
Joon Shin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcriptional Activation ◽  
Orphan Receptor ◽  
Physical Interaction ◽  
Behavioral Deficits ◽  
Neuroprotective Strategy ◽  
Midbrain Dopamine ◽  
6 Hydroxydopamine ◽  
Dual Functions

Parkinson’s disease (PD), primarily caused by selective degeneration of midbrain dopamine (mDA) neurons, is the most prevalent movement disorder, affecting 1–2% of the global population over the age of 65. Currently available pharmacological treatments are largely symptomatic and lose their efficacy over time with accompanying severe side effects such as dyskinesia. Thus, there is an unmet clinical need to develop mechanism-based and/or disease-modifying treatments. Based on the unique dual role of the nuclear orphan receptor Nurr1 for development and maintenance of mDA neurons and their protection from inflammation-induced death, we hypothesize that Nurr1 can be a molecular target for neuroprotective therapeutic development for PD. Here we show successful identification of Nurr1 agonists sharing an identical chemical scaffold, 4-amino-7-chloroquinoline, suggesting a critical structure–activity relationship. In particular, we found that two antimalarial drugs, amodiaquine and chloroquine stimulate the transcriptional function of Nurr1 through physical interaction with its ligand binding domain (LBD). Remarkably, these compounds were able to enhance the contrasting dual functions of Nurr1 by further increasing transcriptional activation of mDA-specific genes and further enhancing transrepression of neurotoxic proinflammatory gene expression in microglia. Importantly, these compounds significantly improved behavioral deficits in 6-hydroxydopamine lesioned rat model of PD without any detectable signs of dyskinesia-like behavior. These findings offer proof of principle that small molecules targeting the Nurr1 LBD can be used as a mechanism-based and neuroprotective strategy for PD.

Apomorphine-induced operant deficits: a neuroleptic-sensitive but drug- and dose-dependent animal model of behavior

1987 ◽  
Vol 2 (4) ◽  
pp. 266-273
Author(s):  
P. Carnoy ◽  
S. Ravard ◽  
D. Hervé ◽  
J.-P. Tassin ◽  
P. Soubrié
Keyword(s):  
Cognitive Processes ◽  
Dopaminergic Neurons ◽  
Operant Behavior ◽  
Fixed Ratio ◽  
Food Delivery ◽  
Behavioral Deficits ◽  
Dopaminergic Transmission ◽  
Dopaminergic Systems ◽  
6 Hydroxydopamine ◽  
Dose Dependent

SummaryIn order to further assess the alterations which might underly behavioral deficits associated with a reduced dopaminergic transmission, the effects of apomorphine at doses thought to stimulate dopaminergic autoreceptors were studied on rat operant behavior.Low doses of apomorphine caused a reward deficit when animais were shifted from continuons reinforcement to fixed ratio schedules of food delivery (fig. 1). This effect could be accounted for by a decreased ability of secondary reinforcers to sustain responding and/or by a disruption of cognitive processes (Table 1). The apomorphine-induced reward deficit in the fixed ratio 4 schedule was reversed by “disinhibitory” neuroleptics including amisulpride, pimozide, pipotiazine and sulpiride, at low to moderate doses. Conversely, “conventional” neuroleptics such as chlorpromazine, fluphenazine, haloperidol, metoclopramide and thioridazine were found inactive in reversing the deficit caused by apomorphine (fig. 2). Results obtained after lesion of dopaminergic neurons by 6-hydroxydopamine suggested that the behavioral deficit induced by apomorphine was related not so much to a reduction in dopaminergic activity in given restricted areas such as the VTA (fig. 3), the nucleus accumbens (fig. 4) or the prefrontal cortex (fig. 5), as to a functional imbalance between mesolimbic and mesocortical dopaminergic systems.

Effect of varenicline on behavioral deficits in a rat model of Parkinson’s disease induced by unilateral 6-hydroxydopamine lesion of substantia nigra

2018 ◽  
Vol 29 (4) ◽  
pp. 327-335
Author(s):  
Rüyal Tan ◽  
Funda Bölükbaşi Hatip ◽  
Öznur Açikalin ◽  
Atsushi Yamauchi ◽  
Yasufumi Kataoka ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Rat Model ◽  
Behavioral Deficits ◽  
6 Hydroxydopamine

scholarly journals The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243452
Author(s):  
Chellappan Praveen Rajneesh ◽  
Jian-Chiun Liou ◽  
Tsung-Hsun Hsieh ◽  
Jia-Hong Lin ◽  
Chih-Wei Peng
Keyword(s):  
Dopaminergic Neurons ◽  
Bladder Dysfunction ◽  
Immunohistochemical Analysis ◽  
Bladder Function ◽  
Target Area ◽  
Behavioral Deficits ◽  
Control Value ◽  
Walking Tests ◽  
6 Hydroxydopamine ◽  
The Brain

Bladder dysfunction is a common phenomenon in Parkinson’s disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results.

scholarly journals Comparison between Tail Suspension Swing Test and Standard Rotation Test in Revealing Early Motor Behavioral Changes and Neurodegeneration in 6-OHDA Hemiparkinsonian Rats

2020 ◽  
Vol 21 (8) ◽  
pp. 2874 ◽  
Author(s):  
Ilaria Rosa ◽  
Davide Di Censo ◽  
Brigida Ranieri ◽  
Giuseppe Di Giovanni ◽  
Eugenio Scarnati ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Behavioral Changes ◽  
Substantia Nigra Pars Compacta ◽  
Motor Asymmetry ◽  
Tail Suspension ◽  
Behavioral Deficits ◽  
Rotation Test ◽  
Post Surgery ◽  
6 Hydroxydopamine ◽  
The Right

The unilateral 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease (PD) is one of the most commonly used in rodents. The anatomical, metabolic, and behavioral changes that occur after severe and stable 6-OHDA lesions have been extensively studied. Here, we investigated whether early motor behavioral deficits can be observed in the first week after the injection of 6-OHDA into the right substantia nigra pars compacta (SNc), and if they were indicative of the severity of the dopaminergic (DAergic) lesion in the SNc and the striatum at different time-points (day 1, 3, 5, 7, 14, 21). With this aim, we used our newly modified tail suspension swing test (TSST), the standard rotation test (RT), and immunohistochemical staining for tyrosine hydroxylase (TH). The TSST, but not the standard RT, revealed a spontaneous motor bias for the 6-OHDA-lesioned rats from the day 1 post-surgery. Both tests detected the motor asymmetry induced by (single and repeated) apomorphine (APO) challenges that correlated, in the first week, with the DAergic neuronal degeneration. The described TSST is fast and easy to perform, and in the drug-free condition is useful for the functional assessment of early motor asymmetry appearing after the 6-OHDA-lesion in the SNc, without the confounding effect of APO challenges.

scholarly journals An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers

2018 ◽  
Vol 10 ◽  
Author(s):  
Clare Rusbridge ◽  
Francisco J. Salguero ◽  
Monique Antoinette David ◽  
Kiterie M. E. Faller ◽  
Jose T. Bras ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Behavioral Deficits

Consideration of the Federal Guidelines for Academic Services for Student-Athletes with Sports-Related Concussion

2012 ◽  
Vol 13 (3) ◽  
pp. 70-78 ◽  
Author(s):  
Bess Sirmon-Taylor ◽  
Anthony P. Salvatore
Keyword(s):  
Student Athletes ◽  
Section 504 ◽  
Return To Play ◽  
Behavioral Deficits ◽  
Prevention Education ◽  
Concussion Management ◽  
School Settings ◽  
Definition Of ◽  
Federal Guidelines ◽  
Academic Services

Abstract Purpose: Federal regulations should be implemented to provide appropriate services for student-athletes who have sustained a concussion, which can result in impaired function in the academic setting. Eligibility guidelines for special education services do not specifically address the significant, but sometimes transient, impairments that can manifest after concussion, which occur in up to 10% of student-athletes. Method: We provide a definition of the word concussion and discuss the eligibility guidelines for traumatic brain injury and other health-impaired under IDEA, as is the use of Section 504. Results: The cognitive-linguistic and behavioral deficits that can occur after concussion can have a significant impact on academic function. We draw comparisons between the clinical presentation of concussion and the eligibility indicators in IDEA and Section 504. Conclusion: Speech-language pathologists are well-positioned to serve on concussion management teams in school settings, providing services including collection of baseline data, intervention and reassessment after a concussion has occurred, prevention education, and legislative advocacy. Until the cultural perception of concussion changes, with increased recognition of the potential consequences, student-athletes are at risk and appropriate implementation of the existing guidelines can assist in preservation of brain function, return to the classroom, and safe return to play.

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