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

ABSTRACT: 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 ?M), homovanillic acid (HVA) (L-TYR 1000 ?M) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 ?M). In striatum L-TYR 250 ?M 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 ?M) and NE (L-TYR 125-250 ?M) in MPFC but lowered P2/P1 for DA (L-TYR 250 ?M) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 ?M) 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.

SUBMITTER: Brodnik ZD

PROVIDER: S-EPMC5544352 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Brodnik Zachary D ZD Double Manda M España Rodrigo A RA Jaskiw George E GE

Neuropharmacology 20170529

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-hydroxyphenylglyco ...[more]

PMID: 28571714

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Project description:BackgroundMouse has been extensively used as a tool for investigating the onset and development of human neurological disorders. As a first step to construct a transgenic mouse model of human brain lesions, it is of fundamental importance to clarify the similarity and divergence of genetic background between non-diseased human and mouse brain tissues.MethodsWe systematically compared, based on large scale integrated microarray data, the transcriptomes of three anatomically distinct brain regions; prefrontal cortex (PFC), hippocampus (HIP) and striatum (STR), across human and mouse. The widely used DAVID web server was used to decipher the biological functions of the highly expressed genes that were identified using a previously reported approach. Venn analysis was used to depict the overlapping ratios of the notably enriched biological process (BP) terms (one-tailed Fisher's exact test and Benjamini correction; adjusted p < 0.01) between two brain tissues. GOSemSim, an R package, was selected to perform GO semantic similarity analysis. Next, we adjusted signal intensities of orthologous genes by the total signals in all samples within species, and used one minus Pearson's correlation coefficient to assess the expression distance. Hierarchical clustering and principal component analysis (PCA) were selected for expression pattern analysis. Lineage specific expressed orthologous genes were identified by comparison of the most extreme sub-datasets across species and further verified using reverse transcription PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR).ResultsWe found that the number of the significantly enriched BP terms of the highly expressed genes in human brain regions is larger than that in mouse corresponding brain regions. The mainly involved BP terms in human brain tissues associated with protein-membrane targeting and selenium metabolism are species-specific. The overlapping ratios of all the significantly enriched BP terms between any two brain tissues across species are lower than that within species, but the pairwise semantic similarities are very high between any two brain tissues from either human or mouse. Hierarchical clustering analysis shows the biological functions of the highly expressed genes in brain tissues are more consistent within species than interspecies; whereas it shows the expression patterns of orthologous genes are evidently conserved between human and mouse equivalent brain tissues. In addition, we identified four orthologous genes (COX5B, WIF1, SLC4A10 and PLA2G7) that are species-specific, which have been widely studied and confirmed to be closely linked with neuro- physiological and pathological functions.ConclusionOur study highlights the similarities and divergences in gene function and expression between human and mouse corresponding brain regions, including PFC, HIP and STR.

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

Publications

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

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