Low Omega-3 Index in Pregnancy Is a Possible Biological Risk Factor for Postpartum Depression

Background

Depression is a common disorder affecting 10–15% women in the postpartum period. Postpartum depression can disrupt early mother-infant interaction, and constitutes a risk factor for early child development. Recently, attention has been drawn to the hypothesis that a low intake of seafood in pregnancy can be a risk factor for postpartum depression. Seafood is a unique dietary source of the marine omega-3 fatty acids and is a natural part of a healthy balanced diet that is especially important during pregnancy.

Methods

In a community based prospective cohort in a municipality in Western Norway, we investigated both nutritional and psychological risk factors for postpartum depression. The source population was all women who were pregnant within the period November 2009 - June 2011. The fatty acid status in red blood cells was assessed in the 28^th gestation week and participants were screened for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) three months after delivery. The aim of the present study was to investigate if a low omega-3 index in pregnancy is a possible risk factor for postpartum depression.

Results

In a simple regression model, the omega-3 index was associated with the EPDS score in a nonlinear inverse manner with an R square of 19. Thus, the low omega-3 index explained 19% of the variance in the EPDS score. The DPA content, DHA content, omega-3 index, omega-3/omega-6 ratio, total HUFA score, and the omega-3 HUFA score were all inversely correlated with the EPDS score. The EPDS scores of participants in the lowest omega-3 index quartile were significantly different to the three other omega-3 index quartiles.

Conclusion

In this study population, a low omega-3 index in late pregnancy was associated with higher depression score three months postpartum.     

Mitochondrial DNA Toxicity in Forebrain Neurons Causes Apoptosis,Neurodegeneration, and Impaired Behavior

Mitochondrial dysfunction underlying changes in neurodegenerative diseases is often associated with apoptosis and a progressive loss of neurons, and damage to the mitochondrial genome is proposed to be involved in such pathologies. In the present study we designed a mouse model that allows us to specifically induce mitochondrial DNA toxicity in the forebrain neurons of adult mice. This is achieved by CaMKIIα-regulated inducible expression of a mutated version of the mitochondrial UNG DNA repair enzyme (mutUNG1). This enzyme is capable of removing thymine from the mitochondrial genome. We demonstrate that a continual generation of apyrimidinic sites causes apoptosis and neuronal death. These defects are associated with behavioral alterations characterized by increased locomotor activity, impaired cognitive abilities, and lack of anxietylike responses. In summary, whereas mitochondrial base substitution and deletions previously have been shown to correlate with premature and natural aging, respectively, we show that a high level of apyrimidinic sites lead to mitochondrial DNA cytotoxicity, which causes apoptosis, followed by neurodegeneration.A variety of both exogenous and endogenous reactive compounds present a constant threat to the integrity of DNA in living cells. DNA damage introduced by such compounds can lead to high and deleterious mutation rates as well as DNA cytotoxicity, both to the nuclear and the mitochondrial genome. This has triggered the evolution of several different DNA repair pathways (28). One is the base excision repair (BER) pathway, which repairs small base alterations that do not distort the DNA helix. Repair of such highly abundant lesions by BER is performed by a multistep process that is initiated by a damage-specific DNA glycosylase, which removes the damaged base. One of these glycosylases is uracil-DNA glycosylase (UDG), which acts to preserve the genome by removing mutagenic uracil residues from the DNA. This glycosylase, as well as the OGG1 glycosylase that is specialized for the removal of oxidized bases, exists in a nuclear and mitochondrial splice form (1, 11, 37, 45). Accordingly, BER of a variety of lesions has been observed in mitochondria (26, 31).Damage to the mitochondrial DNA (mtDNA) can cause respiratory chain deficiency and lead to disorders that have varied phenotypes (35, 41). Many involve neurological features that are often associated with cell loss within specific brain regions. These pathologies, along with the increasing evidence of a decline in mitochondrial function with aging, have raised speculation that key changes in mitochondrial DNA sequences and functions could have a vital role in age-related neurodegenerative diseases (41). This has also been studied in several model organisms. Mouse models with respiratory chain deficient dopamine neurons have demonstrated adult onset Parkinsonism phenotype (16), and cell death induced by mitochondrial toxicity is likely to underlie Alzheimer disease (32). Mitochondrial oxidative stress and accumulation of mtDNA damage are believed to be particularly devastating to postmitotic differentiated tissue, including neurons (30). The mtDNA contains genetic information for 13 polypeptides that are a part of the electron transport chain and for rRNAs and tRNAs that are necessary for mitochondrial protein synthesis. Thus, damage to the mtDNA genome will affect the energetic capacities of the mitochondria and also influence the level of reactive oxygen species (ROS) and ultimately the susceptibility to apoptosis (30, 35).Some recent influential studies have assessed the effect of mtDNA mutagenesis, including small base-pair substitutions and larger mtDNA deletions, on the life span of mice. It was concluded that a massive increase in the frequency of mtDNA base-pair substitutions are required for inducing premature aging, whereas the number of mtDNA deletions coincides better with natural aging (25, 47-49).In the present study, we have combined two novel transgenic mouse models, which allow the induction of a high number of apyrimidinic (AP) sites specifically to the mitochondrial genome in adults simply by the addition of doxycycline to the diet. Such AP sites are created by the expression of a mutated version of mitochondrion-targeted human UDG (abbreviated here as mutUNG1), whereby an amino acid substitution results in an enzyme that removes thymine, in addition to uracil, from DNA (23). The CaMKIIα promoter restricts expression of the mutUNG1 to forebrain neurons (34). We demonstrate that a continuous generation of AP sites leads to apoptosis, accelerated neurodegeneration, and impaired behavior.     

Short‐term costs related to male and female structures in alpine Parnassia palustris

The aim of this study was to investigate the potential costs related to male and female structures in a small, hermaphroditic alpine plant species, Parnassia palustris L. We studied in the field the effect of experimental manipulation of seed set (female structures) as well as anthers and staminodes (male structures) on next year's survival, flowering, seed set and growth. We found no statistically significant differences between the treatments in survival, number of flowers and fruits, fruit/flower ratio, seed number or mean mass per seed the following year. Furthermore, there was no statistically significant difference in growth response between the treatments. These observations indicate both that the manipulations of the flowers the previous year had no effect on growth and that the competition between growth and sexual reproduction was negligible. Our results may reflect small investments in reproduction, abundance of soil resources and/or that all resources saved by the plant one year are not necessarily invested in reproduction or growth next year.     

Effects of snow cover on the timing and success of reproduction in high-Arctic pink-footed geese <Emphasis Type="Italic">Anser brachyrhynchus</Emphasis>

During four breeding seasons, 2003–2006, we studied the relationship between snow cover and nesting performance in pink-footed geese (Anser brachyrhynchus) in a key breeding site on Svalbard. Snow cover in late May, i.e., at the time of egg laying of geese, was derived from MODIS satellite images. Snow cover had a profound cascading effect on reproductive output via the number of nesting pairs and timing of nesting, which affected nest success, while there was only a tendency for a negative effect on clutch size. Hence, we estimated a five-fold difference in the number of young produced (to post-hatching) between years with little snow and years with high snow cover. The results from the study area correlated with whole-population productivity estimates recorded in autumn. Thus, snow cover derived from MODIS satellite images appears to provide a useful indicator of the breeding conditions in the Arctic.     

The effect of estradiol on the cell kinetics in the uterine and cervical epithelium of neonatal mice.

The effect of estradiol-17beta on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle. TC, from 17-9 hr to 15-7 hr, and the duration of S phase, Ts from 6-7 to 5-1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, TC is shortened to 7-4 hr and Ts to 4-5 hr. The shortening of TC at 12 hr is manily due to an effect on TG1, which is shortened from 8-55 hr in untreated animals to 1-8 hr in estradiol treated animals. The TC of cervix epithelium cells in untreated animals was found to be 21-8 hr. After treating the mice for 6 hr with estradiol the tc was now increased to 47 hr and further to 61-2 hr following 12 hr treatment with the hormone. Ts increases from 8-3 hr to 15-2 hr following 6 hr estradiol treatment, and to 15-4 hr after 12 hr treatment. The effect is most pronounced in TG1, which is lengthened from 10-95 hr in untreated animals to 28-1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.     

A comparative description of mitochondrial DNA differentiation in selected avian and other vertebrate genera

Levels of mitochondrial DNA (mtDNA) sequence divergence between species within each of several avian (Anas, Aythya, Dendroica, Melospiza, and Zonotrichia) and nonavian (Lepomis and Hyla) vertebrate genera were compared. An analysis of digestion profiles generated by 13-18 restriction endonucleases indicates little overlap in magnitude of mtDNA divergence for the avian versus nonavian taxa examined. In 55 interspecific comparisons among the avian congeners, the fraction of identical fragment lengths (F) ranged from 0.26 to 0.96 (F = 0.46), and, given certain assumptions, these translate into estimates of nucleotide sequence divergence (p) ranging from 0.007 to 0.088; in 46 comparisons among the fish and amphibian congeners, F values ranged from 0.00 to 0.36 (F = 0.09), yielding estimates of P greater than 0.070. The small mtDNA distances among avian congeners are associated with protein-electrophoretic distances (D values) less than approximately 0.2, while the mtDNA distances among assayed fish and amphibian congeners are associated with D values usually greater than 0.4. Since the conservative pattern of protein differentiation previously reported for many avian versus nonavian taxa now appears to be paralleled by a conservative pattern of mtDNA divergence, it seems increasingly likely that many avian species have shared more recent common ancestors than have their nonavian taxonomic counterparts. However, estimates of avian divergence times derived from mtDNA- and protein-calibrated clocks cannot readily be reconciled with some published dates based on limited fossil remains. If the earlier paleontological interpretations are valid, then protein and mtDNA evolution must be somewhat decelerated in birds. The empirical and conceptual issues raised by these findings are highly analogous to those in the long-standing debate about rates of molecular evolution and times of separation of ancestral hominids from African apes.      

Zinc transporters and the cellular trafficking of zinc

Zinc is an essential nutrient for all organisms because this metal serves as a catalytic or structural cofactor for many different proteins. Zinc-dependent proteins are found in the cytoplasm and within many organelles of the eukaryotic cell including the nucleus, the endoplasmic reticulum, Golgi, secretory vesicles, and mitochondria. Thus, cells require zinc transport mechanisms to allow cells to efficiently accumulate the metal ion and distribute it within the cell. Our current knowledge of these transport systems in eukaryotes is the focus of this review.