Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

<p>Abstract</p> <p>Background</p> <p>Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC) is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5), catechol-<it>O</it>-methyltransferase, and monoamine oxidase (A and B) in the developing human DLPFC (6 weeks -50 years).</p> <p>Results</p> <p>Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p < 0.001) then gradually declined to adulthood. Similarly, mRNA levels of dopamine receptors D2S (p < 0.001) and D2L (p = 0.003) isoforms, monoamine oxidase A (p < 0.001) and catechol-<it>O</it>-methyltransferase (p = 0.024) were significantly higher in neonates and infants as was catechol-<it>O</it>-methyltransferase protein (32 kDa, p = 0.027). In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002) and dopamine D1 receptor protein expression increased throughout development (p < 0.001) with adults having the highest D1 protein levels (p ≤ 0.01). Monoamine oxidase B mRNA and protein (p < 0.001) levels also increased significantly throughout development. Interestingly, dopamine D5 receptor mRNA levels negatively correlated with age (r = -0.31, p = 0.018) in an expression profile opposite to that of the dopamine D1 receptor.</p> <p>Conclusions</p> <p>We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.</p

Food safety and nutritional quality for the prevention of non communicable diseases: The Nutrient, hazard Analysis and Critical Control Point process (NACCP)

Background: The important role of food and nutrition in public health is being increasingly recognized as crucial for its potential impact on health-related quality of life and the economy, both at the societal and individual levels. The prevalence of non-communicable diseases calls for a reformulation of our view of food. The Hazard Analysis and Critical Control Point (HACCP) system, first implemented in the EU with the Directive 43/93/CEE, later replaced by Regulation CE 178/2002 and Regulation CE 852/2004, is the internationally agreed approach for food safety control. Our aim is to develop a new procedure for the assessment of the Nutrient, hazard Analysis and Critical Control Point (NACCP) process, for total quality management (TMQ), and optimize nutritional levels.Methods: NACCP was based on four general principles: i) guarantee of health maintenance; ii) evaluate and assure the nutritional quality of food and TMQ; iii) give correct information to the consumers; iv) ensure an ethical profit. There are three stages for the application of the NACCP process: 1) application of NACCP for quality principles; 2) application of NACCP for health principals; 3) implementation of the NACCP process. The actions are: 1) identification of nutritional markers, which must remain intact throughout the food supply chain; 2) identification of critical control points which must monitored in order to minimize the likelihood of a reduction in quality; 3) establishment of critical limits to maintain adequate levels of nutrient; 4) establishment, and implementation of effective monitoring procedures of critical control points; 5) establishment of corrective actions; 6) identification of metabolic biomarkers; 7) evaluation of the effects of food intake, through the application of specific clinical trials; 8) establishment of procedures for consumer information; 9) implementation of the Health claim Regulation EU 1924/2006; 10) starting a training program.Results and discussion: We calculate the risk assessment as follows: Risk (R) = probability (P) x damage (D). The NACCP process considers the entire food supply chain "from farm to consumer"; in each point of the chain it is necessary implement a tight monitoring in order to guarantee optimal nutritional quality

Omega-3 and Omega-6 Polyunsaturated Fatty Acid Levels and Correlations with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autistic Spectrum Disorder and Typically Developing Controls

BACKGROUND:There is evidence that children with Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Disorder (ASD) have lower omega-3 polyunsaturated fatty acid (n-3 PUFA) levels compared with controls and conflicting evidence regarding omega-6 (n-6) PUFA levels. OBJECTIVES:This study investigated whether erythrocyte n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower and n-6 PUFA arachidonic acid (AA) higher in children with ADHD, ASD and controls, and whether lower n-3 and higher n-6 PUFAs correlated with poorer scores on the Australian Twin Behaviour Rating Scale (ATBRS; ADHD symptoms) and Test of Variable Attention (TOVA) in children with ADHD, and Childhood Autism Rating Scale (CARS) in children with ASD. METHODS:Assessments and blood samples of 565 children aged 3-17 years with ADHD (n = 401), ASD (n = 85) or controls (n = 79) were analysed. One-way ANOVAs with Tukey's post-hoc analysis investigated differences in PUFA levels between groups and Pearson's correlations investigated correlations between PUFA levels and ATBRS, TOVA and CARS scores. RESULTS:Children with ADHD and ASD had lower DHA, EPA and AA, higher AA/EPA ratio and lower n-3/n-6 than controls (P<0.001 except AA between ADHD and controls: P = 0.047). Children with ASD had lower DHA, EPA and AA than children with ADHD (P<0.001 for all comparisons). ATBRS scores correlated negatively with EPA (r = -.294, P<0.001), DHA (r = -.424, P<0.001), n-3/n-6 (r = -.477, P<0.001) and positively with AA/EPA (r = .222, P <.01). TOVA scores correlated positively with DHA (r = .610, P<0.001), EPA (r = .418, P<0.001) AA (r = .199, P<0.001), and n-3/n-6 (r = .509, P<0.001) and negatively with AA/EPA (r = -.243, P<0.001). CARS scores correlated significantly with DHA (r = .328, P = 0.002), EPA (r = -.225, P = 0.038) and AA (r = .251, P = 0.021). CONCLUSIONS:Children with ADHD and ASD had low levels of EPA, DHA and AA and high ratio of n-6/n-3 PUFAs and these correlated significantly with symptoms. Future research should further investigate abnormal fatty acid metabolism in these disorders