Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

Guillot, Thomas S.; Miller, Gary W.

doi:10.1007/s12035-009-8059-y

Cited by 177 publications

(135 citation statements)

References 223 publications

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“…DA levels in the PFC are in synaptic terminals of neurons arising in the VTA and are directly depending on TH levels in these neurons (Del Arco and Mora 2009). Since TH is at normal levels in these neurons in spite of the impaired DA levels in PS rats, we speculate that other steps in the DA synthesis and storage metabolism is impaired such as DA transporters VMAT2 or DAT or the degradation machinery (MAO, COMT) (Guillot and Miller 2009) that still justify the decreased levels of DA in cortical structures of adult PS rats.…”

Section: Discussionmentioning

confidence: 89%

Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

et al. 2009

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The development of the central nervous system can be permanently affected by insults received during the perinatal period, predisposing the organism to long-term behavioral and neurochemical abnormalities. Rats exposed to different types of stress during the last week of gestation produce offspring that show several alterations, many of which have been attributed to changes in dopamine (DA) neurotransmission that could serve as the neurochemical basis for the development of neuropsychiatric disorders. Employing an immunocytochemical approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation as well as the expression of the rate limiting enzyme in DA synthesis, tyrosine hydroxylase (TH) in mesencephalic areas of the brains of prenatally stressed (PS) offspring at different postnatal ages. Main results show that stress exerted to the gestant mother produces permanent effect in the ontogenetic expression of key factors related to the DA metabolism mainly in the ventral tegmental area (VTA) of the mesencephalon. The immunocytochemical expression of the transcription factor Nurr1 shows an increase at postnatal days (PNDs) 7, 28, and 60 whereas Pitx3 shows a decrease at PND 28 and an increase at 60 PND. The rate limiting step in DA synthesis, the enzyme TH shows a decrease at PND 7 to reach control levels at PNDs 28 and 60. The increase of TFs might be up-regulating TH in order to restore DA levels that were previously seen to be normal before puberty. The area selectivity of the increase of the TFs toward VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional, and reward behavior impairments in the adult life.

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Section: Discussionmentioning

confidence: 89%

Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

et al. 2009

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“…Furthermore, there is some evidence that inflammatory cytokines and inflammation may negatively affect expression and function of the vesicular monoamine transporter 2 (Felger and Miller, 2012;Kazumori et al, 2004). Normal vesicular sequestration and release is particularly important in DAergic cells due to the risk of auto-oxidation of DA and the formation of neurotoxic quinones and free radicals (Guillot and Miller, 2009). Therefore, an early increase in DA synthesis or release by cytokines, as observed during week 2 of IFN-a administration in the present study, could contribute to oxidative stress, leading to subsequent decreases in DA synthesis and impaired release.…”

Section: Discussionmentioning

confidence: 99%

Chronic Interferon-α Decreases Dopamine 2 Receptor Binding and Striatal Dopamine Release in Association with Anhedonia-Like Behavior in Nonhuman Primates

Felger

Mun

Kimmel

et al. 2013

Neuropsychopharmacol

173

141

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Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal DA function, eight rhesus monkeys (four male, four female) were administered interferon (IFN)-α (20 MIU/m(2) s.c.) or saline for 4 weeks. In vivo microdialysis was used to investigate IFN-α effects on DA release in the striatum. In addition, positron emission tomography (PET) with [(11)C]raclopride was used to examine IFN-α-induced changes in DA2 receptor (D2R) binding potential before and after intravenous amphetamine administration. DA transporter binding was measured by PET using [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane. Anhedonia-like behavior (sucrose consumption) was assessed during saline and IFN-α administration. In vivo microdialysis demonstrated decreased release of DA after 4 weeks of IFN-α administration compared with saline. PET neuroimaging also revealed decreased DA release after 4 weeks of IFN-α as evidenced by reduced displacement of [(11)C]raclopride following amphetamine administration. In addition, 4 weeks of IFN-α was associated with decreased D2R binding but no change in the DA transporter. Sucrose consumption was reduced during IFN-α administration and was correlated with decreased DA release at 4 weeks as measured by in vivo microdialysis. Taken together, these findings indicate that chronic peripheral IFN-α exposure reduces striatal DA release in association with anhedonia-like behavior in nonhuman primates. Future studies examining the mechanisms of cytokine effects on DA release and potential therapeutic strategies to reverse these changes are warranted.

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“…Once inside the neuron, MPP+ is able to inhibit complex 1 of the mitochondrial electron transport chain, resulting in the release of ROS as well as reduced ATP production. Storing into vesicles can decrease MPP+ toxicity [40][41][42]. Additionally, MPP+ stored in vesicles is thought to expel DA out into the intercellular space where it can be metabolized into a number of compounds, including toxic metabolites, such as DOPAL and where it is can be subjected to superoxide radical (5-cysteinyl-DA) and hydroxyl radical (6-OHDA) attack [43,44].…”

Section: Mptpmentioning

confidence: 99%

The Effect of Treadmill Exercise on Expression of α-synuclein and miRNA in MPTP Induced-mouse Models of Parkinson’s Disease

Moon¹,

Choi²,

Oh³

et al. 2017

Exerc Sci

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Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

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Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

Cited by 177 publications

References 223 publications

Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

Chronic Interferon-α Decreases Dopamine 2 Receptor Binding and Striatal Dopamine Release in Association with Anhedonia-Like Behavior in Nonhuman Primates

The Effect of Treadmill Exercise on Expression of α-synuclein and miRNA in MPTP Induced-mouse Models of Parkinson’s Disease

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