Sex and strain influence the effect of ethanol on central monoamines.

Boone, Ericka; Cook, Melloni N.; Hou, Xu; Jones, Brian Christopher

doi:10.15288/jsa.1997.58.590

Cited by 21 publications

(14 citation statements)

References 26 publications

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“…Briefly, the ventral midbrain was dissected as described by Boone et al (2007) weighed and combined with 200 μL of ultrapure nitric acid (OmiTrace ® , EM Science, NXO407-1) in a 0.5 mL polypropylene micro-centrifuge tube. Brain regions were digested for 48 h in a 60 °C sand bath and then re-suspended to 400 μL with nanopure water.…”

Section: Methodsmentioning

confidence: 99%

Systems analysis of genetic variation in MPTP neurotoxicity in mice

et al. 2013

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We analyzed genetic variation in severity of neuronal damage using the known dopaminergic neurotoxicant, MPTP, as a prototypical chemical denervation agent. Male mice from ten members of the BXD family of recombinant inbred strains received 12.5 mg/kg MPTP s.c. (vs. saline) and 48 h later brains were taken for multiple related biochemical analyses. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, and serotonin and its metabolite, 5-HIAAA, were analyzed by HPLC. DA turnover was assessed using DOPAC/DA and HVA/DA ratios. Striatal tyrosine hydroxylase (TH), glial fibrilary acidic protein (GFAP), and iron content in ventral midbrain were quantified. All dopamine measures, as well as TH and GFAP, demonstrated wide, genotype-dependent differences in response to MPTP. Serotonin was largely unaffected. Principal components analysis (PC) on difference values, saline minus MPTP, for DA, DOPAC, HVA, and TH, yielded a dominant principal component. The PC trait residuals for each genotype were compared against complementary expression data for striatum of the same strains. Three transcripts representing Mtap2, Lancl 1, and Kansl1l were highly correlated with the PC, as was the difference score, MPTP minus saline for GFAP. This systems approach to the study of environmental neurotoxicants holds promise to define individual genetic differences that contribute to variability in susceptibility to risk factors for diseases such as Parkinson’s disease.

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Section: Methodsmentioning

confidence: 99%

Systems analysis of genetic variation in MPTP neurotoxicity in mice

et al. 2013

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“…All animals were killed by CO 2 suffocation and placed on ice until the brain was removed within 6 h. The brains were dissected into medial prefrontal cortex (PFC), caudate-putamen (CP), nucleus accumbens (NA) and ventral midbrain (VMB) as described by Boone et al (1997). Frozen brain regions were wet digested using our standard protocol (Pinero et al 2001;Jones et al 2003).…”

Section: Tissue Harvestmentioning

confidence: 99%

Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice

Jones

McCarthy

Beard

et al. 2006

Nutritional Neuroscience

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Copper and zinc are trace nutrients essential for normal brain function, yet an excess of these elements can be toxic. It is important therefore that these metals be closely regulated. We recently conducted a quantitative trait loci (QTL) analysis to identify chromosomal regions in the mouse containing possible regulatory genes. The animals came from 15 strains of the BXD/Ty recombinant inbred (RI) strain panel and the brain regions analyzed were frontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. Several QTL were identified for copper and/or zinc, most notably on chromosomes 1, 8, 16 and 17. Genetic correlational analysis also revealed associations between these metals and dopamine, cocaine responses, saccharine preference, immune response and seizure susceptibility. Notably, the QTL on chromosome 17 is also associated with seizure susceptibility and contains the histocompatibility H2 complex. This work shows that regulation of zinc and copper is under polygenic influence and is intimately related to CNS function. Future work will reveal genes underlying the QTL and how they interact with other genes and the environment. More importantly, revelation of the genetic underpinnings of copper and zinc brain homeostasis will aid our understanding of neurological diseases that are related to copper and zinc imbalance.

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“…All animals were killed by CO 2 suffocation and placed on ice until the brain was removed within 6 h. The brains were dissected into medial prefrontal cortex (PFC), caudate-putamen (CP), nucleus accumbens (NA) and ventral midbrain (VMB) as described by Boone et al (1997). The VMB was dissected by making a 458 from vertical, rostral-caudal, cut from the posterior end of the hypothalamus (facing up).…”

Section: Tissue Harvestmentioning

confidence: 99%

Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice

Jones

Reed

Hitzemann

et al. 2003

Nutritional Neuroscience

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Male and female mice from 15 of the BXD/Ty recombinant inbred strain panel were examined for regional brain and liver iron content. Brain regions included medial prefrontal cortex, nucleus accumbens, caudate-putamen and ventral midbrain. Our focal tissue was the ventral midbrain, containing the ventral tegmentum and substantia nigra. This area contains the perikarya of the dopamine neurons that project to nucleus accumbens and caudate-putamen. Genetic correlations between ventral midbrain and liver iron content were not statistically significant, suggesting that peripheral and central iron regulatory systems are largely independent. Correlations between ventral midbrain iron and iron in the caudate-putamen and nucleus accumbens, but not the prefrontal cortex were moderately high and significant. Ventral midbrain and liver iron contents were subjected to quantitative trait loci analysis to identify associated chromosomal locations. This analysis revealed several suggestive loci for iron content in ventral midbrain but fewer loci for liver. Genetic correlations between ventral midbrain iron and published dopamine functional indices were significant, suggesting a link between ventral midbrain iron status and central dopamine neurobiology. This work shows the value of quantitative genetic analysis in the neurobiology of iron and in showing the close association between ventral midbrain iron and nigrostriatal/mesolimbic dopamine function.

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Sex and strain influence the effect of ethanol on central monoamines.

Cited by 21 publications

References 26 publications

Systems analysis of genetic variation in MPTP neurotoxicity in mice

Systems analysis of genetic variation in MPTP neurotoxicity in mice

Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice

Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice

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