scholarly journals Release parameters during progressive degeneration of dopamine neurons in a mouse model reveal earlier impairment of spontaneous than forced behaviors

2019 ◽  
Vol 150 (1) ◽  
pp. 56-73 ◽  
Author(s):  
Yuan‐Hao Chen ◽  
Tsung‐Hsun Hsieh ◽  
Tung‐Tai Kuo ◽  
Jen‐Hsin Kao ◽  
Kuo‐Hsing Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dopamine Neurons ◽  
Progressive Degeneration

scholarly journals Effect of insulin on excitatory synaptic transmission onto dopamine neurons of the ventral tegmental area in a mouse model of hyperinsulinemia

2013 ◽  
Vol 3 (12) ◽  
pp. e97-e97 ◽  
Author(s):  
S Liu ◽  
G Labouèbe ◽  
S Karunakaran ◽  
S M Clee ◽  
S L Borgland
Keyword(s):  
Mouse Model ◽  
Synaptic Transmission ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Excitatory Synaptic Transmission ◽  
Ventral Tegmental

Simvastatin Prevents Neurodegeneration in the MPTP Mouse Model of Parkinson’s Disease via Inhibition of A1 Reactive Astrocytes

2021 ◽  
pp. 1-8
Author(s):  
Ren-Wei Du ◽  
Wen-Guang Bu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Underlying Mechanism ◽  
Reactive Astrocytes ◽  
Dopamine Neurons ◽  
Neuron Death ◽  
Neurologic Disorders

Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.

scholarly journals Fentanyl vapor self-administration model in mice to study opioid addiction

2020 ◽  
Vol 6 (32) ◽  
pp. eabc0413 ◽  
Author(s):  
K. Moussawi ◽  
M. M. Ortiz ◽  
S. C. Gantz ◽  
B. J. Tunstall ◽  
R. C. N. Marchette ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opioid Addiction ◽  
Dopamine Neurons ◽  
Drug Intake ◽  
Self Administration ◽  
Protracted Abstinence ◽  
Electrophysiological Recordings ◽  
Lower Amplitude ◽  
The Many ◽  
Intravenous Catheterization

Intravenous drug self-administration is considered the “gold standard” model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABAB receptor–dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

Estrogen receptors and gonadal steroids in vulnerability and protection of dopamine neurons in a mouse model of Parkinson’s disease

2011 ◽  
Vol 61 (4) ◽  
pp. 583-591 ◽  
Author(s):  
Sara Al-Sweidi ◽  
Marc Morissette ◽  
Mélanie Bourque ◽  
Thérèse Di Paolo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Estrogen Receptors ◽  
Gonadal Steroids ◽  
Dopamine Neurons

scholarly journals PET imaging studies show enhanced expression of mGluR5 and inflammatory response during progressive degeneration in ALS mouse model expressing SOD1-G93A gene

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna-Liisa Brownell ◽  
Darshini Kuruppu ◽  
Kun-Eek Kil ◽  
Kimmo Jokivarsi ◽  
Pekka Poutiainen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Pet Imaging ◽  
Imaging Studies ◽  
Progressive Degeneration ◽  
Enhanced Expression

scholarly journals Pharmacological Antagonism of Kainate Receptor Rescues Dysfunction and Loss of Dopamine Neurons in a Mouse Model of Human Parkin-induced Toxicity

2020 ◽  
Author(s):  
Maria Regoni ◽  
Stefano Cattaneo ◽  
Daniela Mercatelli ◽  
Salvatore Novello ◽  
Alice Passoni ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neuroprotective Effect ◽  
Chronic Administration ◽  
Dopamine Neurons ◽  
Kainate Receptors ◽  
Substantia Nigra Pars Compacta ◽  
Gene Encoding ◽  
Neuroprotective Therapy

Abstract BackgroundMutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP), a neurodegenerative disease characterized by dysfunction and death of dopamine (DA) neurons in the substantia nigra pars compacta. Since a neuroprotective therapy for ARJP does not exist, research efforts aimed at discovering potential targets for neuroprotection are critically needed.A previous study demonstrated that loss of parkin function or expression of parkin mutants associated with ARJP causesan accumulation of glutamate kainate receptors (KARs) in human brain tissues and an increase of KAR-mediated currents in neuronsin vitro. MethodsBased on the hypothesisthat such KAR hyper-activation may contribute to the death of nigralDA neurons, we investigated the effect of KAR antagonism on the DA neuron dysfunction and death that occur in the parkinQ311X mouse, a model of human parkin-induced toxicity. ResultsWe found that early accumulation of KARs occurs in the DA neurons of the parkinQ311X mouse model and that chronic administration of the KAR antagonist UBP310 prevents DA neuron loss. This neuroprotective effect was associated with rescue of the abnormal firing rate of nigral DA neurons and downregulation of GluK2, the key KAR subunit. ConclusionsThis study provides novel evidence ofa causal role of glutamate KARs in the DA neuron dysfunction and loss occurring in a mouse model of human parkin-induced toxicity. Our results support KAR as a potential target in the development of a neuroprotective therapy for ARJP.

scholarly journals Loss of Midbrain Dopamine Neurons and Altered Apomorphine EEG Effects in the 5xFAD Mouse Model of Alzheimer’s Disease

2019 ◽  
Vol 70 (1) ◽  
pp. 241-256
Author(s):  
Vasily Vorobyov ◽  
Boris Bakharev ◽  
Natalia Medvinskaya ◽  
Inna Nesterova ◽  
Alexander Samokhin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dopamine Neurons ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mouse ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Norfluoxetine Prevents Degeneration of Dopamine Neurons by Inhibiting Microglia-Derived Oxidative Stress in an MPTP Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Kyung In Kim ◽  
Young Cheul Chung ◽  
Byung Kwan Jin
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Microglial Activation ◽  
Dopamine Neurons ◽  
Activated Microglia ◽  
Nigrostriatal Dopamine Neurons

Neuroinflammation is the neuropathological feature of Parkinson’s disease (PD) and causes microglial activation and activated microglia-derived oxidative stress in the PD patients and PD animal models, resulting in neurodegeneration. The present study examined whether norfluoxetine (a metabolite of fluoxetine) could regulate neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD and rescue dopamine neurons. Analysis by tyrosine hydroxylase (TH) immunohistochemistry demonstrated that norfluoxetine prevents degeneration of nigrostriatal dopamine neurons in vivo in MPTP-lesioned mice compared to vehicle-treated MPTP-lesioned control mice. MAC-1 immunostaining and hydroethidine histochemical staining showed that norfluoxetine neuroprotection is accompanied by inhibiting MPTP-induced microglial activation and activated microglia-derived reactive oxygen species production in vivo, respectively. In the separate experiments, treatment with norfluoxetine inhibited NADPH oxidase activation and nitrate production in LPS-treated cortical microglial cultures in vitro. Collectively, these in vivo and in vitro results suggest that norfluoxetine could be employed as a novel therapeutic agent for treating PD, which is associated with neuroinflammation and microglia-derived oxidative stress.

The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant activity amongst VTA dopamine neurons in both familiar and novel space

2017 ◽  
Vol 330 ◽  
pp. 1-7 ◽  
Author(s):  
Mahboubeh Ahmadi ◽  
Jean-Philippe Dufour ◽  
Erich Seifritz ◽  
Javad Mirnajafi-Zadeh ◽  
Bechara J. Saab
Keyword(s):  
Mouse Model ◽  
Dopamine Neurons ◽  
Ptz Kindling

scholarly journals A new mouse model for retinal degeneration due to Fam161a deficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Avigail Beryozkin ◽  
Chen Matsevich ◽  
Alexey Obolensky ◽  
Corinne Kostic ◽  
Yvan Arsenijevic ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinal Degeneration ◽  
Outer Segment ◽  
Ganglion Cells ◽  
Photoreceptor Outer Segment ◽  
Tem Analysis ◽  
Retinal Degenerations ◽  
Progressive Degeneration ◽  
Transmission Electron ◽  
Lacz Staining

AbstractFAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161atm1b/tm1b, lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the Fam161a promoter. LacZ staining was evident in ganglion cells, inner and outer nuclear layers and inner and outer-segments of photoreceptors in KO mice. No immunofluorescence staining of Fam161a was evident in the KO retina. Visual acuity and electroretinographic (ERG) responses showed a gradual decrease between the ages of 1 and 8 months. Optical coherence tomography (OCT) showed thinning of the whole retina. Hypoautofluorescence and hyperautofluorescence pigments was observed in retinas of older mice. Histological analysis revealed a progressive degeneration of photoreceptors along time and high-resolution transmission electron microscopy (TEM) analysis showed that photoreceptor outer segment disks were disorganized in a perpendicular orientation and outer segment base was wider and shorter than in WT mice. Molecular degenerative markers, such as microglia and CALPAIN-2, appear already in a 1-month old KO retina. These results indicate that a homozygous Fam161a frameshift mutation affects retinal function and causes retinal degeneration. This model will be used for gene therapy treatment in the future.

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