Reply to “Reproducing Increased Dopamine with Infection To Evaluate the Role of Parasite-Encoded Tyrosine Hydroxylase Activity”

McConkey, Glenn A.; Peers, Chris; Prandovszky, Emese

doi:10.1128/iai.00642-15

Cited by 11 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, our discovery of a significant disruption in the regulation of the glutamate pathway could predict changes in other neurotransmitters. Indeed, while contradictory reports exist for the ability of Toxoplasma to manipulate dopamine [ 70 – 72 ], recent work investigating GAD67 localization at the presynaptic terminal demonstrates disruption in GABA signaling and a decrease in seizure threshold [ 73 ]. Decreased inhibition and increased glutamatergic signaling is a clear pathway to seizures and occurs in patients with Toxoplasmic encephalitis [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii

et al. 2016

View full text Add to dashboard Cite

The immune privileged nature of the CNS can make it vulnerable to chronic and latent infections. Little is known about the effects of lifelong brain infections, and thus inflammation, on the neurological health of the host. Toxoplasma gondii is a parasite that can infect any mammalian nucleated cell with average worldwide seroprevalence rates of 30%. Infection by Toxoplasma is characterized by the lifelong presence of parasitic cysts within neurons in the brain, requiring a competent immune system to prevent parasite reactivation and encephalitis. In the immunocompetent individual, Toxoplasma infection is largely asymptomatic, however many recent studies suggest a strong correlation with certain neurodegenerative and psychiatric disorders. Here, we demonstrate a significant reduction in the primary astrocytic glutamate transporter, GLT-1, following infection with Toxoplasma. Using microdialysis of the murine frontal cortex over the course of infection, a significant increase in extracellular concentrations of glutamate is observed. Consistent with glutamate dysregulation, analysis of neurons reveal changes in morphology including a reduction in dendritic spines, VGlut1 and NeuN immunoreactivity. Furthermore, behavioral testing and EEG recordings point to significant changes in neuronal output. Finally, these changes in neuronal connectivity are dependent on infection-induced downregulation of GLT-1 as treatment with the ß-lactam antibiotic ceftriaxone, rescues extracellular glutamate concentrations, neuronal pathology and function. Altogether, these data demonstrate that following an infection with T. gondii, the delicate regulation of glutamate by astrocytes is disrupted and accounts for a range of deficits observed in chronic infection.

show abstract

Section: Discussionmentioning

confidence: 99%

GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Dies passt zu dem zwei Jahre später erhobenen Befund, dass dopaminerge Neuronen, die in vitro durch Toxoplasmen infiziert worden waren, mehr Dopamin freisetzen (67) und würde zudem sparsam erklären, warum Dopaminantagonisten das gesteigerte Neugierverhalten bei toxoplasmoseinfizierten Ratten blockieren können (71). Einschränkend ist zum gegenwärtigen Zeitpunkt allerdings zu sagen, dass die Hypothese einer toxoplasmeninduzierten dopaminergen Hyperaktivität von einer zweiten Arbeitsgruppe nicht repliziert werden konnte (84) und daher zur Zeit heftig umstritten ist (52,85). Zudem zeigte eine genauere in-vitro-Studie an dopaminergen toxoplasmeninfizierten Neuronen vom Herbst 2015 kaum erhöhte zytosolische Konzentrationen von freigesetztem Dopamin sowie eine unbeeinträchtigte Aufnahme von Dopamin in die Vesikel ("cellular DA packaging appeared unchanged"; 50, S. 50).…”

Section: Geist and Gehirnunclassified

Protozoen und Persönlichkeitsstörungen, die Psychiatrie und der Ursprung der Menschheit

Spitzer¹

2016

Nervenheilkunde

View full text Add to dashboard Cite

“…Two genes (AAH1 and AAH2) which have similar sequences to tyrosine hydroxylase, a mammalian enzyme essential in the rate-limiting step in dopamine synthesis [159], may be responsible for the hyperdopaminergic drive in the brain. Yet, the link between Toxoplasma infection and dopamine levels has not been widely reproducible [160].…”

Section: Proximate Mechanisms In Toxoplasma Infectionmentioning

confidence: 99%

Role of oxytocin in mate-choice copying of female rats

Chua¹

View full text Add to dashboard Cite

and the Ministry of Education. My deepest gratitude to my supervisor, Associate Professor Ajai Vyas, for his unwavering guidance and invaluable mentorship, which allowed me to grow as a researcher. I am indebted to my lab mates, without whom this project would not have come to fruition. Magdalena was a joy to work with throughout the matechoice copying experiments and bore the brunt of my bad jokes. Wen Han patiently showed me the ropes and extended support whenever required. He, Si Jie and Max were always ready to lend a helping hand, which was much needed in perfusion experiments. I am thankful for Cher and the other vets at the Animal Research Facility, who helped collect male rat urine and took great care of the rats. Finally, I am forever grateful to my family and friends for their emotional and moral support throughout this journey.

show abstract

Reply to “Reproducing Increased Dopamine with Infection To Evaluate the Role of Parasite-Encoded Tyrosine Hydroxylase Activity”

Cited by 11 publications

References 9 publications

GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii

GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii

Protozoen und Persönlichkeitsstörungen, die Psychiatrie und der Ursprung der Menschheit

Role of oxytocin in mate-choice copying of female rats

Contact Info

Product

Resources

About