Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex.

The prefrontal cortex (PFC) is a crucial hub for the flexible modulation of recent memories (executive functions) as well as for the stable organization of remote memories. Dopamine in the PFC is implicated in both these processes and genetic variants affecting its neurotransmission might control the unique balance between cognitive stability and flexibility present in each individual. Functional genetic variants in the catechol-O-methyltransferase (COMT) gene result in a different catabolism of dopamine in the PFC. However, despite the established role played by COMT genetic variation in executive functions, its impact on remote memory formation and recall is still poorly explored. Here we report that transgenic mice overexpressing the human COMT-Val gene (COMT-Val-tg) present exaggerated remote memories (>50 days) while having unaltered recent memories (<24 h). COMT selectively and reversibly modulated the recall of remote memories as silencing COMT Val overexpression starting from 30 days after the initial aversive conditioning normalized remote memories. COMT genetic overactivity produced a selective overdrive of the endocannabinoid system within the PFC, but not in the striatum and hippocampus, which was associated with enhanced remote memories. Indeed, acute pharmacological blockade of CB1 receptors was sufficient to rescue the altered remote memory recall in COMT-Val-tg mice and increased PFC dopamine levels. These results demonstrate that COMT genetic variations modulate the retrieval of remote memories through the dysregulation of the endocannabinoid system in the PFC.

Adolescence is the starting point of sex-dichotomous COMT genetic effects.

The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice (COMT-/-), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT-by-sex divergent effects started to appear at the cortical level during puberty. These biochemical differences were absent in infancy. Finally, developmental cognitive assessment in 22q11DS and COMT knockout mice established that COMT-by-sex-dichotomous effects in executive functions were already apparent in adolescence. These findings uncover that genetic variations severely reducing COMT result in detrimental cortical and cognitive development selectively in females after their sexual maturity. This highlights the importance of taking into account the combined effect of genetics, sex and developmental stage.

Dopamine transporter (DAT) genetic hypofunction in mice produces alterations consistent with ADHD but not schizophrenia or bipolar disorder.

ADHD, schizophrenia and bipolar disorder are psychiatric diseases with a strong genetic component which share dopaminergic alterations. Dopamine transporter (DAT) genetics might be potentially implicated in all these disorders. However, in contrast to DAT absence, the effects of DAT hypofunction especially in developmental trajectories have been scarcely addressed. Thus, we comprehensively studied DAT hypofunctional mice (DAT+/-) from adolescence to adulthood to disentangle DAT-dependent alterations in the development of psychiatric-relevant phenotypes. From pre-adolescence onward, DAT+/- displayed a hyperactive phenotype, while responses to external stimuli and sensorimotor gating abilities were unaltered. General cognitive impairments in adolescent DAT+/- were partially ameliorated during adulthood in males but not in females. Despite this, attentional and impulsivity deficits were evident in DAT+/- adult males. At the molecular level, DAT+/- mice showed a reduced expression of Homer1a in the prefrontal cortex, while other brain regions as well as Arc and Homer1b expression were mostly unaffected. Amphetamine treatments reverted DAT+/- hyperactivity and rescued cognitive deficits. Moreover, amphetamine shifted DAT-dependent Homer1a altered expression from prefrontal cortex to striatal regions. These behavioral and molecular phenotypes indicate that a genetic-driven DAT hypofunction alters neurodevelopmental trajectories consistent with ADHD, but not with schizophrenia and bipolar disorders.

Breast milk composition and infant nutrient intakes during the first 12 months of life.

BACKGROUND/OBJECTIVES: The objective of this study was to quantify human milk supply and intake of breastfed infants up to age 12 months. In addition, human milk composition was quantified per energetic macronutrient and fatty-acid composition in a subsample of lactating mothers. SUBJECTS/METHODS: One hundred and seventy-four Italian breastfed children were followed using test-weighing and 3-day food protocols from birth to age 12 months. From a subsample of 30 mothers breast milk samples were collected at child ages one (T1), two (T2), three (T3) and six (T6) months, and were analyzed for the amount of protein, digestible carbohydrates, total lipids and fatty-acid composition. RESULTS: One hundred and forty-two (82%) filled in at least one 3-day food protocol within the first 12 months of life and complied with test-weighing of all milk feeds. The number of valid food protocols declined from 126 infants at 1 month to 77 at 12 months of age. Only galactose, non-protein nitrogen and protein decreased significantly from age 1 to age 6 months of lactation. Maternal body mass index and age affected fatty-acid levels in human milk. Median human milk intake decreased from 625 ml at T1, over 724 ml at T3 to 477 ml/day at T6. Average energy and %energy from protein intake per day increased from 419 kcal (s.d. 99) and 8.4% (1.0) at T1, respectively, to 860 kcal (145) and 16.1% (2.6) at T12. CONCLUSIONS: These data provide a reference range of nutrient intakes in breastfed infants and may provide guidance for defining optimal nutrient intakes for infants that cannot be fully breastfed.

Bovine colostrum: changes in lipid constituents in the first 5 days after parturition.

Despite the great interest paid to protein components in colostrum, fat also plays an important role in the supply of essential nutrients to provide energy, increase metabolism, and protect the newborn calf against microbial infections. This work aimed to elucidate levels of different fat components in colostrum, in particular fatty acid (FA), triglyceride (TG), cholesterol, and phospholipid contents. Colostrum samples from primiparous and multiparous (3-5 lactations) Holstein dams, fed the same ration indoors, were collected on the first 5d after parturition, analyzed, and compared with milk samples from the same cows collected at 5mo of lactation. Fat content during the first 5d of milking did not vary. However, the proportion of short-chain saturated FA increased and that of long-chain FA decreased. The concentration of n-3 FA was higher on the first day of calving than on the other days, with clear differences in the number and type of n-3 FA. Conjugated linoleic isomers and trans FA slowly increased from d 1 to 5, reaching a maximum at 5mo of lactation. Changes in the distribution profile of TG were observed as lactation progressed, with a shift from a prevalence of high-carbon-number TG (C48-50) on d 1 to a bimodal distribution (maxima at C38 and C50) on d 5, characteristic of mid-lactation milk. Cholesterol content was high in the first hours after calving and rapidly decreased within 48h. Colostrum sampled on d 1 also had a high content of phospholipids. Phosphatidylethanolamine and sphingomyelin were, respectively, lower and higher in the first 5d than in mid-lactation milk. The influence of lactation number on colostrum fat composition was also considered and significant results were obtained for all FA groups (except for polyunsaturated and n-6 FA) and TG content.

Exploring polymorphisms and effects of candidate genes on milk fat quality in dairy sheep.

The aim of the present study was to investigate the genetic control of the fatty acid (FA) composition in milk from 3 breeds of sheep: Altamurana, Gentile di Puglia, and Sarda. Single nucleotide polymorphisms within genes, encoding enzymes putatively involved in the synthesis and metabolism of milk fat, were selected for analysis, and the allele substitution effects were determined for 16 genes, which were polymorphic in the 3 sheep breeds, upon the milk fat composition. Four genes (alpha-1-antichymotrypsin-2; diacylglycerol O-acyltransferase homolog-2; propionyl Coenzyme A carboxylase, beta polypeptide; and insulin-like growth factor-I) play a role in the desaturation of stearic FA into polyunsaturated fatty acids. Furthermore, 2 genes (growth hormone receptor and zona pellucida glycoprotein-2) affect the variability of the total fat content in addition to the butyric and stearic FA profile, and the fatty acid synthetase gene has an influence on the medium-chain FA. Milk FA profiles play an important role in dairy sheep farming because they have a large effect on cheese characteristics and also because sheep milk may be marketed as a source of nutraceuticals because it contains higher levels of conjugated linoleic acid than milk from other ruminants. The current study evaluated the global effects of a large number of single nucleotide polymorphisms and haplotypes on traits that are not commonly investigated in sheep but that are potentially very useful for improving milk quality.

Short communication: Effect of stearoyl-coenzyme A desaturase polymorphism on fatty acid composition of milk.

The effect of the stearoyl-CoA desaturase (SCD) gene on milk fatty acid composition was tested. Cows of 3 breeds of northern Italy, Piedmontese, Valdostana, and Jersey, were genotyped at exon 5 of the SCD gene. This has been suggested as a primary candidate gene to change the proportion of saturated vs. unsaturated fatty acids in milk, wherein a single nucleotide polymorphism (C/T) gives rise to a different AA codon. It was possible to ascribe a reduced desaturase activity to the T allele only in the case of caproleic and myristoleic fatty acids. In contrast with the findings of SCD effects on carcass fat, it was not possible to confirm the higher desaturation activity of this single nucleotide polymorphism on long-chain fatty acids, due to the different pathways that originate milk fatty acids of different carbon length; long-chain fatty acids are highly influenced by the complex metabolic events that affect the ingested nutrients during their transfer to milk fat.

Study on the influence of pasture on volatile fraction of ewes' dairy products by solid-phase microextraction and gas chromatography-mass spectrometry.

The detection of markers of identification of the geographical origin of food is an attractive challenge and, as far as dairy products are concerned, this paper represents a contribution to this field. In this research the influence of feed on the volatile compound composition was investigated on milk, 2-mo-old cheese (Caciotta), and whey cheese (ricotta) obtained from the same flock of Sarda ewes, under standardized technological conditions. Three different types of pasture (mixture of Lolium perenne and Trifolium squarrosum; rough pasture; Avena sativa) were studied. Solid-phase microextraction combined with gas chromatography-mass spectrometry was used and principal component analysis was applied for statistical evaluation of the data set. The volatile composition was significantly affected by the type of pasture independently of the type of cheese and the ripening period. Moreover, a marker of rough pasture, tentatively identified as (E,E)-3,7,11-tri-methyl-2,4,10-dodecatriene, was detected only in milk and cheeses produced when the ewe flock grazed on that pasture.

Effectiveness of chemometric techniques in discrimination of lactobacillus helveticus biotypes from natural dairy starter cultures on the basis of phenotypic characteristics

Lactobacillus helveticus is the dominant organism in natural starter cultures used for the production of typical Italian cheeses. In this study, 74 L. helveticus strains, isolated from grana and provolone cheese natural whey starters, were distinguished with respect to their origin by using both cell wall protein profiles and chemometric evaluation of some phenotypic parameters, such as the ability to acidify cultures and the presence of nonspecific proteolytic and peptidase activities. Cell wall protein patterns allowed L. helveticus strains to be distinguished with respect to their source of isolation. Among the different phenotypes studied, no single specific parameter permitted the two groups of strains to be separated. A good discrimination between the two groups of L. helveticus species was obtained by multivariate statistical techniques, which permitted the extraction of all of the discriminating information retained in the phenotypic activities. Associations between strain phenotype expression and dairy environmental ecosystem source are discussed.