The influx of neutral amino acids into the porcine brain during development: a positron emission tomography study

Brust, Peter; Vorwieger, Gerd; Walter, Bernd; Füchtner, F.; Stark, Holger; Kuwabara, Hiroto; Herzau, Michael; Opfermann, Thomas; Steinbach, Jörg; Ganapathy, Vadivel; Bauer, Reinhard

doi:10.1016/j.devbrainres.2004.07.002

Cited by 7 publications

(3 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In baboons without pretreatment, the mean K i values for the caudate and putamen of control animals were 6.9 ± 1.2 and 7.7 ± 1.8 × 10 -3 min -1 [35]. The K i value also reflects the blood-brain barrier (BBB) influx rate and the transport function of system L, which is composed of the L-type amino acid transporter 1 (LAT1) and 4F2hc [43]. System L transports large neutral amino acids including leucine, tryptophan, tyrosine, phenylalanine, and amino acid related drugs such as L -DOPA, alpha-methyldopa, melphalan, and gabapentin [44].…”

Section: Discussionmentioning

confidence: 99%

Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

et al. 2011

View full text Add to dashboard Cite

BackgroundWe evaluated the utility of L-3,4-dihydroxy-6-[18F]fluoro-phenylalanine ([18F]FDOPA) positron emission tomography (PET) as a method for assessing the severity of dopaminergic dysfunction in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats by comparing it with quantitative biochemical, immunohistochemical, and behavioral measurements.MethodsDifferent doses of 6-OHDA (0, 7, 14, and 28 μg) were unilaterally injected into the right striatum of male Sprague-Dawley rats. Dopaminergic functional activity in the striatum was assessed by [18F]FDOPA-PET, measurement of striatal dopamine (DA) and DA metabolite levels, tyrosine hydroxylase (TH) immunostaining, and methamphetamine-induced rotational testing.ResultsAccumulation of [18F]FDOPA in the bilateral striatum was observed in rats pretreated with both aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT) inhibitors. Unilateral intrastriatal injection of 6-OHDA produced a significant site-specific reduction in [18F]FDOPA accumulation. The topological distribution pattern of [18F]FDOPA accumulation in the ipsilateral striatum agreed well with the pattern in TH-stained corresponding sections. A significant positive relationship was found between Patlak plot Ki values and striatal levels of DA and its metabolites (r = 0.958). A significant negative correlation was found between both Ki values (r = -0.639) and levels of DA and its metabolites (r = -0.719) and the number of methamphetamine-induced rotations.ConclusionsKi values determined using [18F]FDOPA-PET correlated significantly with the severity of dopaminergic dysfunction. [18F]FDOPA-PET makes it possible to perform longitudinal evaluation of dopaminergic function in 6-OHDA-lesioned rats, which is useful in the development of new drugs and therapies for Parkinson's disease (PD).

show abstract

Section: Discussionmentioning

confidence: 99%

Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Kinetics for the cerebral metabolism of FDOPA in living pig resembles closely earlier findings in rat, monkey and human with this widely used PET tracer (Danielsen et al, 1999). Optimal methods for quantification of FDOPA uptake have been established in pig brain , and using FDOPA/PET, developmental changes in the influx of large neutral amino acids (Brust et al, 2004a), DOPA decarboxylase activity (Brust et al, 2004b), and vulnerability of dopamine systems of traumatic brain injury (Walter et al, 2004) have been assessed in neonate and young adult pigs. Furthermore, treatment with antipsychotic medication blocking dopamine D 2 receptors acutely stimulates the influx of FDOPA to striatum of living pigs (Danielsen et al, 2001a).…”

Section: Article In Pressmentioning

confidence: 95%

The use of pigs in neuroscience: Modeling brain disorders

Lind

Moustgaard

Jelsing

et al. 2007

Neuroscience & Biobehavioral Reviews

443

407

View full text Add to dashboard Cite

“…Moreover, the expression of LAT1 was found to be regulated by amino acid availability. Brust et al (2004) indicated that LAT1 underlies developmental changes after birth causing a decrease in the permeability of the BBB permeability for those amino acids required during brain development, however, there is no strong correlation between the amino acid supply to the brain and the demands of protein synthesis in the brain tissue (Brust et al, 2004). Thus, whether LAT1 expression affects protein synthesis requires further study.…”

Section: Discussionmentioning

confidence: 97%

Dietary protein, energy and arginine affect LAT1 expression in forebrain white matter differently

Yin

et al. 2010

Animal

View full text Add to dashboard Cite

L-type amino acid transporter-1 (LAT1) transports large, branched-chain, aromatic and neutral amino acids. About 64 Duroc × Landrace × Yorkshire pigs were used to study the effects of dietary crude protein (CP), energy and arginine on LAT1 expression in forebrain. The results showed that LAT1 expression in forebrain was sensitive to different levels of CP, energy and arginine. On the basis of Western blot analysis, a lower level of LAT1 presented in the brain tissues of pigs fed the low dietary CP diet (P < 0.05), a higher level were found in pigs fed the higher CP diet, with moderate to intense staining seen in pigs fed the diet plus 1% arginine. In contrast, pigs fed the control-energy diet had weak LAT1 expression, and those fed the diet supplemented with 1% arginine showed lowest LAT1 expression (P < 0.05). These results showed that LAT1 was highly expressed in the forebrain, and expression of LAT1 was affected by dietary protein, energy and arginine differently.

show abstract

The influx of neutral amino acids into the porcine brain during development: a positron emission tomography study

Cited by 7 publications

References 71 publications

Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

The use of pigs in neuroscience: Modeling brain disorders

Dietary protein, energy and arginine affect LAT1 expression in forebrain white matter differently

Contact Info

Product

Resources

About