Primary Culture of Mouse Dopaminergic Neurons

Gaven, Florence; Marin, Philippe; Claeysen, Sylvie

doi:10.3791/51751

Cited by 56 publications

(41 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By using the primary culture of SNc neurons (Gaven et al, 2014), the effect of glutamate on the SNc cells under normal and energy-deficient conditions can be studied (Novelli et al, 1988). Using brain slice cultures or co-culture systems that comprise of SNc-STN system, one can investigate the conditions under which excitotoxic runaway effect is observed (Renaud and Martinoli, 2016).…”

Section: Suggesting Further Experimentsmentioning

confidence: 99%

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2018

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). A full understanding of the underlying pathogenesis of this cell loss is unavailable, though a number of mechanisms have been indicated in the literature. A couple of these mechanisms, however, show potential for the development of radical and promising PD therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc cells by virtue of their excessive energy demands; the other is the excitotoxicity caused by excessive glutamate release onto SNc by an overactive Subthalamic Nucleus (STN). To investigate the latter hypothesis computationally, we developed a spiking neuron network model of the SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in a 'stress' variable; when the stress in a SNc neuron exceeds a stress threshold the neuron dies. The model shows that the interaction between SNc and STN involves a positive feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway effect that leads to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned PD mechanisms: metabolic vulnerability and glutamate excitotoxicity. Our simulation results show that the excitotoxic cause of SNc cell loss in PD might be initiated by weak excitotoxicity mediated by energy deficit, followed by strong excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies are simulated in the model to test their efficacy in slowing down or arresting SNc cell loss. Among the current therapeutics,

show abstract

Section: Suggesting Further Experimentsmentioning

confidence: 99%

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Primary DA neurons were isolated from a one-day-old SD rat, and the ventral tegmental area (VTA) were dissociated using a previously described protocol. 30,63 In brief, the VTA was dissected from the mesencephalon of a one-day-old SD rat, which mainly comprised DA neurons and neuroglial cells. This preparation was incubated with 0.125% trypsin at 37 C in a CO 2 incubator for 3 min before adding the same volume of serumfree culture medium to terminate the action of the trypsin.…”

Section: Da Neuronal Culturementioning

confidence: 99%

Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Primary mesencephalic culture was prepared from E13 mouse ventral mesencephalon according to methods described previously (Gaven, Marin, & Claeysen, 2014). Cells were plated into PDL-coated plastic coverslips at a density of 1.5 × 10 5 cells/cm 2 .…”

Section: Primary Mesencephalic Culturementioning

confidence: 99%

SIRPα deficiency accelerates the pathologic process in models of Parkinson disease

Wang

Ding

et al. 2019

Glia

View full text Add to dashboard Cite

Microglia‐mediated neuroinflammation is a crucial pathophysiological contributor to several aging‐related neurodegenerative disorders, including Parkinson's disease (PD). During the process of aging or stress, microglia undergoes several transcriptional and morphological changes that contribute to aberrant immunological responses, which is known as priming. Key molecules involved in the process, however, are not clearly defined. In the present study, we have demonstrated that level of microglial signal regulatory protein α (SIRPα) decreased during aging or inflammatory challenge. Functional studies suggested that downregulation of SIRPα released the brake of inflammatory response in microglia, revealing an inhibitory effect of SIRPα in microglial activation. Furthermore, we assessed the impact of SIRPα downregulation in PD pathogenesis using both cell culture and animal models. Our results showed that SIRPα deficiency resulted in abnormal inflammatory response and phagocytic activity of microglia, which in turn, further accelerated degeneration of dopaminergic neurons in 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine or lipopolysaccharides mice models. These results collectively demonstrate that dysregulation of SIRPα signaling in microglia during aging plays a critical role in the pathogenesis of age‐related neurological disorders such as PD.

show abstract

Primary Culture of Mouse Dopaminergic Neurons

Cited by 56 publications

References 34 publications

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry

SIRPα deficiency accelerates the pathologic process in models of Parkinson disease

Contact Info

Product

Resources

About