MAO Activity in Rat Brain Stem and Cerebral Cortex following Acute and Chronic Treatment with &lt;i&gt;L&lt;/i&gt;-Dopa and Ethanol + &lt;i&gt;L&lt;/i&gt;-Dopa

Renis, Marcella; Giovine, A.; Bertolino, A.

doi:10.1159/000136715

Cited by 9 publications

(2 citation statements)

References 27 publications

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“…This effect resembles an observation by us (Jenkins et al, 1980) where we found that pretreatment of mice with L-DOPA or L-DOPA+B rendered them one day later, more sensitive to the locomotor stimulant effects of L-DOPA § In that study also, the enhanced response was not due to a change in DA receptor sensitivity, but was caused by increased levels of DOPA (and DA) in the brain a~er the challenge dose. The cause of the change in the levels of L-DOPA in the present study is unknown, but could involve a fall in L-amino acid decarboxylase levels (Dairman et al, 1971;Lancaster et al, 1973), a fail in brain monoamineoxidase and/or catechol-O-methyltransferase levels (Renis et al, 1977;Lancaster et al, 1973) or the formation of pharmacologically active metabolites, such as tetrahydroisoquinolines (Sourkes, 1971;Coscia et al, 1977) or transaminated derivatives (Sandier et al, 1974). B administered chronically by itself also influenced the response to L-DOPA+B challenge on the first day of withdrawal.…”

Section: Discussionmentioning

confidence: 73%

Chronic L-DOPA treatment of mice: A behavioural and biochemical study

Bailey

Crisp

Jackson

et al. 1981

J. Neural Transmission

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Mice were pretreated once daily with L-DOPA (200 mg/kg) plus benserazide (B) (50 mg/kg) for ten days and challenged with various doses of L-DOPA + B on the first, fourth or sixteenth days of withdrawal. L-DOPA + B-pretreated mice were more sensitive the locomotor stimulant effect of L-DOPA + B challenge one and four days, but not sixteen days after withdrawal. The enhanced response was most marked on the first day of withdrawal. Other mice, pretreated once daily with B (50 mg/kg), responded one day after the tenth dose with a slightly enhanced response to L-DOPA + B challenge compared to the response to vehicle-pretreated animals. Moreover, vehicle-pretreated mice challenged with B alone, were significantly less active than those challenged with vehicle. On the first day of withdrawal, the L-DOPA + B-pretreated animals were supersensitive to locomotor stimulant effects of apomorphine but subsensitive to dexamphetamine (Bailey et al., 1979). On the fourth day of withdrawal, there were no differences in the responses of the L-DOPA + B-pretreated mice compared to the vehicle-pretreated mice, to apomorphine or apomorphine plus clonidine, but L-DOPA + B-pretreated mice were still subsensitive to the locomotor stimulant effects of dexamphetamine. Clonidine produced a dose-dependent, but similar, degree of hypothermia in both pretreatment groups. On the first and fourth days of withdrawal L-DOPA + B-pretreated mice exhibited higher brain levels of dopamine (DA) and DOPA than vehicle-pretreated mice in response to an acute dose of L-DOPA + B. The biochemical results suggest that the enhanced locomotor response to L-DOPA + B in L-DOPA + B-pretreated mice is probably dependent on changes in the amount of L-DOPA (and DA) available in the brain. Moreover, it is not ruled out that some of the effects of L-DOPA + B pretreatment were due to the B alone. Some of the enhanced response to L-DOPA + B on the first day of withdrawal may have been dependent on the same mechanism as that underlying the apparent supersensitivity to apomorphine. The subsensitive response to dexamphetamine would appear to be independent of changes in post-synaptic DA and alpha-adrenergic receptor sensitivity.

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Section: Discussionmentioning

confidence: 73%

Chronic L-DOPA treatment of mice: A behavioural and biochemical study

Bailey

Crisp

Jackson

et al. 1981

J. Neural Transmission

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“…A possible explanation could be that decrease in MAO-A and MAO-B levels was prompted by the supplementation of the differentiation media with DA. It has been reported that chronic treatment with L-DOPA leads to inhibition of MAO activity, an effect opposite of that of acute L-DOPA treatment [57]. However, a similar inhibitory effect would then be expected in the control MDNS.…”

Section: Discussionmentioning

confidence: 86%

Cellular alterations identified in pluripotent stem cell-derived midbrain spheroids generated from a female patient with progressive external ophthalmoplegia and parkinsonism who carries a novel variation (p.Q811R) in the POLG1 gene

Chumarina

Russ

Azevedo

et al. 2019

acta neuropathol commun

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Variations in the POLG1 gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma, have recently been associated with Parkinson's disease (PD), especially in patients diagnosed with progressive external ophthalmoplegia (PEO). However, the majority of the studies reporting this association mainly focused on the genetic identification of the variation in POLG1 in PD patient primary cells, and determination of mitochondrial DNA copy number, providing little information about the cellular alterations existing in patient brain cells, in particular dopaminergic neurons. Therefore, through the use of induced pluripotent stem cells (iPSCs), we assessed cellular alterations in novel p.Q811R POLG1 (POLG1 Q811R) variant midbrain dopaminergic neuron-containing spheroids (MDNS) from a female patient who developed early-onset PD, and compared them to cultures derived from a healthy control of the same gender. Both POLG1 variant and control MDNS contained functional midbrain regionalized TH/FOXA2-positive dopaminergic neurons, capable of releasing dopamine. Western blot analysis identified the presence of high molecular weight oligomeric alpha-synuclein in POLG1 Q811R MDNS compared to control cultures. In order to assess POLG1 Q811R-related cellular alterations within the MDNS, we applied massspectrometry based quantitative proteomic analysis. In total, 6749 proteins were identified, with 61 significantly differentially expressed between POLG1 Q811R and control samples. Pro-and anti-inflammatory signaling and pathways involved in energy metabolism were altered. Notably, increased glycolysis in POLG1 Q811R MDNS was suggested by the increase in PFKM and LDHA levels and confirmed using functional analysis of glycolytic rate and oxygen consumption levels. Our results validate the use of iPSCs to assess cellular alterations in relation to PD pathogenesis, in a unique PD patient carrying a novel p.Q811R variation in POLG1, and identify several altered pathways that may be relevant to PD pathogenesis.

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