Pprocesses That Couple Amino Acid Availability to Neurotransmitter Synthesis and Release

Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

doi:10.1007/978-3-642-73175-4_11

Cited by 5 publications

(3 citation statements)

References 67 publications

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“…For example, decreased HVA levels were also found in the nucleus accumbens, although no significant effect was found on HVA levels in the striatum. The different results for the accumbens and striatum are consistent with other findings (Acworth et al, 1988) and are to be expected given the higher rate of dopamine turnover in the accumbens (Bannon and Roth, 1983). The absence of any effect on norepinephrine is also consistent with previous work demonstrating that norepinephrine levels are relatively insensitive to alterations in precursor (Irie and Wurtman, 1987).…”

Section: Discussionsupporting

confidence: 91%

An animal model of early-treated PKU

et al. 1994

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Phenylketonuria (PKU) is a genetic disorder in which the hydroxylation of phenylalanine (Phe) to tyrosine is severely disrupted. If PKU is left untreated, severe mental retardation results. The accepted treatment is to restrict dietary intake of Phe. It has generally been thought that cognitive impairments are prevented if levels of Phe in plasma are maintained at or below five times the normal level. However, we recently documented that children treated early and continuously for PKU or children mildly hyperphenylalaninemic, who have levels of Phe in plasma approximately three to five times normal, still have cognitive impairments. These impairments are specific to the functions of frontal cortex (A. Diamond, W. Hurwitz, E. Lee, W. Grover, and C. Minarcik, unpublished observations). To investigate the mechanism underlying these cognitive deficits, an animal model of this condition was developed and characterized. Thirty-six rat pups were divided into three groups. The first group was treated pre- and postnatally with Phe and alpha-methylphenylalanine (a phenylalanine hydroxylase inhibitor). The second group was injected postnatally with Phe and alpha- methylphenylalanine. The third group received postnatal control injections. The mild plasma Phe elevations in the two experimental groups produced significant behavioral and neurochemical effects. Both experimental groups were impaired on a task dependent on frontal cortex, delayed alternation. Levels of dopamine, homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole acetic acid (5-HIAA) were measured in medial prefrontal cortex, anterior cingulate cortex, striatum, and nucleus accumbens. The largest neurochemical reductions observed were in HVA and were in the two frontal cortical areas (medial prefrontal cortex and anterior cingulate cortex). There were modest reductions in HVA in the nucleus accumbens but no significant changes in HVA, or in any other metabolite or neurotransmitter, in the striatum. The levels of 5-HIAA were also reduced in all brain regions examined. There was no effect on norepinephrine in any of the four regions examined. Reduced levels of HVA in medial prefrontal cortex were the only neurochemical effect that significantly correlated with every measure of performance on the delayed alternation task. This study provides evidence of deleterious effects from mild elevations in the levels of Phe in plasma previously considered small enough to be safe. These effects include impaired performance on a cognitive task dependent on frontal cortex and reduced HVA levels in frontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 91%

An animal model of early-treated PKU

et al. 1994

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“…It may have some clinical use for treatment of Parkinson's disease and depression. 159 Tyrosine has seven water non-exchangeable protons, four from the phenyl ring and three from its aliphatic side chain. The four phenyl ring protons give a multiplet spread between 6.89 and 7.19 ppm.…”

Section: Tyrosine (Tyr)mentioning

confidence: 99%

Proton NMR chemical shifts and coupling constants for brain metabolites

2000

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“…In early microdialysis studies, systemically administered L-TYR was reported to modestly elevate extracellular striatal DA but not DOPAC (Acworth et al, 1988;During et al, 1988;During et al, 1989). Those data, however, were collected under anesthesia, within a few hours of probe implantation.…”

Section: Discussionmentioning

confidence: 99%

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

et al. 2017

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We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250 – 1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500 – 1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125 – 250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5 – 50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and / or disordered L-TYR transport have been implicated.

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Pprocesses That Couple Amino Acid Availability to Neurotransmitter Synthesis and Release

Cited by 5 publications

References 67 publications

An animal model of early-treated PKU

An animal model of early-treated PKU

Proton NMR chemical shifts and coupling constants for brain metabolites

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

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