Biomedical subjects

Susan E Carlson

Publications and source records attributed to Susan E Carlson.

13 recordsLinked to original sources

PubMed2007

Maternal parity and diet (n-3) polyunsaturated fatty acid concentration influence accretion of brain phospholipid docosahexaenoic acid in developing rats.

The long-chain PUFA, docosahexaenoic acid [22:6(n-3), DHA], a major component of neuronal membrane phospholipids, accumulates in brain during late prenatal and early neonatal development and is essential for optimal attentional and cognitive function. Because all nutrition is supplied to the developing fetus/neonate by the mother and maternal DHA status is affected by parity, this study examined the effects of maternal diet and parity on DHA accretion in the developing brain. Whole brain total phospholipid fatty acid composition was determined by TLC and GC in weanling male Long-Evans rats (n = 5) from the 1st, 2nd, 3rd, or 4th litters of dams fed diets containing alpha-linolenic acid (ALA), containing ALA and preformed DHA (ALA + DHA), or lacking ALA (low-ALA). First-litter low-ALA offspring exhibited a decrease in phospholipid fatty acid DHA content to 68% of 1st-litter ALA pups. DHA in 2nd-litter low-ALA pups was further decreased to 55% of 1st-litter ALA pups, but further decreases were not observed in subsequent litters. DHA levels increased 15-20% in 2nd to 4th-litter ALA + DHA pups and 11% in 4th-litter ALA pups compared with 1st-litter ALA pups. These findings demonstrate that maternal diet and parity interact to affect offspring brain DHA status and suggest that maternal multiparity may place offspring at greater risk of decreased accretion of brain DHA if the maternal diet contains insufficient (n-3) PUFA.

Aging↗

PubMed2007

Specific brain regions of female rats are differentially depleted of docosahexaenoic acid by reproductive activity and an (n-3) fatty acid-deficient diet.

Low tissue levels of (n-3) PUFA, particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. Brain DHA content is depleted in female rats undergoing pregnancy and lactation when the diet supplies inadequate (n-3) PUFA. In this study, the effects of DHA depletion as a result of reproductive activity and an (n-3) PUFA-deficient diet were examined in 8 specific brain regions of female rats after undergoing 2 sequential reproductive cycles. Virgin females, fed the alpha-linolenic acid (ALA)-containing or deficient (low-ALA) diets for a commensurate duration (13 wk) served as a control for reproduction. Total phospholipid composition of each brain region was determined at weaning (postnatal d 21) by TLC/GC. The regional PUFA composition of ALA virgins was similar to that previously measured in male rats. All brain regions examined were affected by reproductive activity and/or the low-ALA diet; however, the magnitude of the loss of DHA and compensatory incorporation of docosapentaenoic acid [(n-6) DPA, 22:5(n-6)] varied among brain regions. In low-ALA parous dams, frontal cortex (77% of ALA virgin) and temporal lobe (83% of ALA virgin), regions involved in cognition and affect, were among those exhibiting the greatest depletion of DHA. Caudate-putamen also exhibited significant depletion of DHA (82% of ALA virgin), whereas only (n-6) DPA levels were altered in ventral striatum, hypothalamus, hippocampus, and cerebellum. This pattern of changes in regional DHA and (n-6) DPA content suggests that specific neuronal systems may be differentially affected by depletion of brain DHA in the postpartum organism.

Animals↗

PubMed2006

Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology.

The principle omega-3 fatty acid in brain, docosahexaenoic acid (DHA), accumulates in the brain during perinatal cortical expansion and maturation. Animal studies have demonstrated that reductions in perinatal brain DHA accrual are associated with deficits in neuronal arborization, multiple indices of synaptic pathology including deficits in serotonin and mesocorticolimbic dopamine neurotransmission, neurocognitive deficits, and elevated behavioral indices of anxiety, aggression, and depression. In primates and humans, preterm delivery is associated with deficits in fetal cortical DHA accrual, and children/adolescents born preterm exhibit deficits in cortical gray matter maturation, neurocognitive deficits particularly in the realm of attention, and increased risk for attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. Individuals diagnosed with ADHD or schizophrenia exhibit deficits in cortical gray matter maturation, and medications found to be efficacious in the treatment of these disorders increase cortical and striatal dopamine neurotransmission. These associations in conjunction with intervention trials showing enhanced cortical visual acuity and cognitive outcomes in preterm and term infants fed DHA, suggest that perinatal deficits in brain DHA accrual may represent a preventable neurodevelopmental risk factor for the subsequent emergence of psychopathology.

Animals↗

PubMed2006

Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats.

Insufficient availability of n-3 polyunsaturated fatty acids (PUFAs) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain and is associated with sub-optimal sensory and cognitive function in humans, altered behavior in animals, and may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia. This study examined the effects of variation in dietary availability of n-3 PUFAs on brain fatty acid composition and the consequent effects on locomotor activity in male and female Long-Evans rats. Rats were raised from conception using purified diets and breeding protocols designed to produce four groups with distinct brain phospholipid compositions varying in DHA content and/or the proportion of n-3 and n-6 PUFAs. Locomotor behavior was measured for a 2-h period on postnatal days 28, 42, 56, and 70. In males, decreased brain DHA produced alterations in activity that were most pronounced post-adolescence and with the greatest decrease in DHA. However, the behavioral effects in males were not linearly related to brain DHA level. In contrast, no significant effects of variation in brain fatty acid composition were observed in females. This suggests that variation in brain DHA content produces sex-specific alterations in locomotor activity and that the neurochemical alterations underlying the observed behavioral changes vary depending on the degree of DHA depletion.

Age Factors↗

PubMed2006

Reduced brain DHA content after a single reproductive cycle in female rats fed a diet deficient in N-3 polyunsaturated fatty acids.

BACKGROUND: Low levels of n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA, 22:6n3), are implicated in postpartum depression. METHODS: The effects of pregnancy and lactation on brain phospholipid fatty acid content were determined in female rats fed diets containing sufficient (control) or negligible (deficient) alpha-linolenic acid (18:3n-3), the dietary precursor of DHA, beginning at conception. Female virgins, fed the diets for 6 weeks, served as control animals. Whole brain total phospholipid composition was determined at weaning by GC. RESULTS: Brain DHA content of postpartum dams fed the deficient diet was decreased by 21% compared with age-matched virgin control animals, with a reciprocal increase in docosapentaenoic acid (22:5n6) to 243%. CONCLUSIONS: Under dietary conditions supplying inadequate n-3 PUFAs, maternal brain DHA content can be reduced after a single reproductive cycle. This depletion may affect neuronal function and thus the sensitivity of the postpartum organism to stress.

Animals↗

PubMed2006

Sub-chronic antipsychotic drug treatment does not alter brain phospholipid fatty acid composition in rats.

Altered membrane phospholipid fatty acid composition is reported in schizophrenia and appears to be reduced by antipsychotic drug treatment. To determine whether antipsychotic drugs have a direct effect on brain phospholipid fatty acid composition, the effects of sub-chronic treatment with a "typical" and an "atypical" antipsychotic drug were determined in adult male Sprague-Dawley rats. Rats were treated with haloperidol (1 mg/kg), clozapine (20 mg/kg) or vehicle daily for 21 days. Whole brain total phospholipid composition was determined by gas chromatography. No alterations in brain phospholipid composition were produced by either drug. This suggests that the apparent normalization of membrane phospholipids observed in drug-treated schizophrenic patients is not due to a direct pharmacological effect of these drugs nor can the pharmacological effects of these drugs occurring in this time frame be attributed to alterations in neuronal membrane fatty acid composition.

Analysis of Variance↗

PubMed2006

Differential effects of modulation of docosahexaenoic acid content during development in specific regions of rat brain.

Variation in brain FA composition, particularly decreased DHA (22:6n-3), affects neurodevelopment, altering visual, attentional, and cognitive functions, and is implicated in several neuropsychiatric disorders. To further understand how specific brain processes and systems are affected by variation in brain DHA content, we sought to determine whether specific brain regions were differentially affected by treatments that alter brain DHA content. Adult male Long-Evans rats were raised from conception using diet/breeding treatments to produce four groups with distinct brain phospholipid compositions. Total phospholipid FA composition was determined in whole brain and 15 brain regions by TLC/GC. Brain regions exhibited significantly different DHA contents, with the highest levels observed in the frontal cortex and the lowest in the substantia nigra/ventral tegmental area. Increased availability of DHA resulted in increased DHA content only in the olfactory bulb, parietal cortex, and substantia nigra/ventral tegmental area. In contrast, treatment that decreased whole-brain DHA levels decreased DHA content in all brain regions except the thalamus, dorsal midbrain, and the substantia nigra/ventral tegmental area. Alterations in DHA level were accompanied by changes in docosapentaenoic acid (n-6 DPA, 22:5n-6) content; however, the change in DHA and n-6 DPA was nonreciprocal in some brain regions. These findings demonstrate that the FA compositions of specific brain regions are differentially affected by variation in DHA availability during development. These differential effects may contribute to the specific neurochemical and behavioral effects observed in animals with variation in brain DHA content.

Animals↗

PubMed2006

N-3 fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations.

Several randomized clinical studies in infants born preterm and at term have explored the effects on visual acuity development of postnatal supplementation with various sources of docosahexaenoic acid (DHA). Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula. Differences in the sensitivity of the test may also be relevant in discussions of whether the effects of DHA on visual acuity are transient or persistent. A smaller number of studies have attempted to study the effects of DHA on cognitive development. The major focus of this article is to review the types of methods that have been used to evaluate the effects of DHA on cognition and to provide the rationale for measures that are a better conceptual fit. Research is needed (1) to probe the effects of variable DHA exposure on infant and child development, (2) to measure outcomes that better relate to preschool and school-age cognitive function, and (3) to reinforce, and in some cases demonstrate, links between specific infant and preschool measures of cognitive development. We strongly encourage collaborations with developmental cognitive neuroscientists to facilitate these research goals.

Child, Preschool↗

PubMed2006

Diet (n-3) polyunsaturated fatty acid content and parity interact to alter maternal rat brain phospholipid fatty acid composition.

Low tissue levels of (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. The effects of 1-4 sequential reproductive cycles on maternal brain phospholipid fatty acid composition were determined in female rats fed diets containing alpha-linolenic acid (ALA), containing ALA and pre-formed DHA (ALA+DHA), or lacking ALA (low-ALA). Virgin females, fed the diets for commensurate durations served as a control for reproduction. Whole-brain total phospholipid composition was determined at weaning by TLC/GC. A single reproductive cycle on the low-ALA diet decreased brain DHA content by 18% compared to ALA primiparas (P < 0.05), accompanied by incorporation of docosapentaenoic acid ((n-6) DPA, 22:5(n-6)) to 280% of ALA primiparas (P < 0.05). DHA was not further decreased after subsequent cycles; however, there was an additional increase in (n-6) DPA after the second cycle (P < 0.05). Brain DHA of virgin females fed the low-ALA diet for 27 wk decreased 15% (P < 0.05), but was accompanied by a more modest increase in (n-6) DPA than in parous low-ALA dams (P < 0.05). Virgin females and parous dams fed the diet containing ALA+DHA exhibited only minor changes in brain fatty acid composition. These observations demonstrate that brain DHA content of adult animals is vulnerable to depletion under dietary conditions that supply inadequate (n-3) PUFAs, that this effect is augmented by the physiological demands of pregnancy and lactation, and that maternal diet and parity interact to affect maternal brain PUFA status.

Animals↗

PubMed2004

Decreased brain docosahexaenoic acid during development alters dopamine-related behaviors in adult rats that are differentially affected by dietary remediation.

Docosahexaenoic acid (DHA) is a major component of neuronal membranes. In rats, low brain levels of DHA during development produce alterations in the mesocortical and mesolimbic dopamine systems. In this study, male Long-Evans rats (n = 6-7 per group) were raised from conception on diets with (control) or without alpha-linolenic acid, the dietary precursor of DHA. The deficient diet reduced brain DHA to 80% of that of control animals at maturity. At weaning (P21), half of the pups from each deficient litter were changed to a remediation diet enriched in DHA by the addition of fish oil. Beginning at P56, rats were subjected to a battery of behavioral tests. Catalepsy induced by haloperidol (3mg/kg, i.p.) in deficient animals was 49% of that observed in control animals (P < 0.05). Catalepsy in remediated animals was similar to that observed for control animals. In a test of locomotor activity in a novel environment, deficient animals exhibited 187% of the activity of control animals (P < 0.05). Locomotor activity stimulated by d-amphetamine (0.5mg/kg, s.c.) in deficient animals was 145% of that observed in control animals (P < 0.05). Basal and amphetamine-stimulated activity of remediated animals was similar to that of deficient animals. Response to a thermal stimulus was not different between groups. These findings demonstrate that rats exposed from conception to a diet that produces a relatively modest decrease in brain DHA content exhibit alterations in adult behavior indicative of altered dopaminergic function. Some of these behavioral alterations were reversed by dietary remediation initiated at weaning.

Amphetamine↗

PubMed2003

High-DHA eggs: feasibility as a means to enhance circulating DHA in mother and infant.

Dietary DHA enhances infant attention and visual development. Because the DHA content of red blood cells and plasma lipids varies approximately threefold in pregnancy, maternal DHA status may influence subsequent infant function. It would be feasible to study the effects of higher maternal DHA intake on infant development if dietary intake of DHA could be increased by a reliable means. This study was designed to determine whether women provided with one dozen high-DHA hen eggs (135 mg DHA/egg) would consume the eggs and have higher blood DHA levels than women consuming ordinary eggs (18 mg DHA/egg). The study was a randomized, double-masked comparison of the effect of eggs with different concentrations of DHA on intake and blood lipid DHA content of women and their infants. A third nonrandomized group ate few eggs. In this study, DHA intake reported from eggs was eightfold higher in the high-DHA egg group compared to the ordinary egg group. Including all groups, DHA intake ranged from 0 to 284 mg/d. In this intake range, maternal blood lipid DHA content at enrollment best predicted DHA content at delivery, accounting for 36.5 and 51.7% of the variance in ordinary and high-DHA egg intake groups, respectively. The high-DHA vs. ordinary egg groups had similar maternal and cord blood lipid DHA, but there was a positive relationship between maternal plasma phospholipid DHA and daily DHA intake from eggs controlled for study duration (r = 0.278, P = 0.048). DHA intake and birth weight were also correlated (r = 0.299, P = 0.041). High-DHA eggs were well accepted and increased DHA intake. Other benefits of DHA intake during pregnancy were also suggested.

Adolescent↗

PubMed2003

A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy.

OBJECTIVE: To hypothesize that higher intake of docosahexaenoic acid, an n-3 long chain polyunsaturated fatty acid, would increase duration of gestation and birth weight in US women. METHODS: This was a randomized, double-blind, controlled, clinical trial. Subjects were enrolled in an ambulatory clinic where they received prenatal care. This was a population-based sample. Most subjects received government assistance for medical care and most were black (73%). Subjects were enrolled between the 24th and 28th week of pregnancy and consumed docosahexaenoic acid (33 or 133 mg) from eggs until parturition. Gestational age and birth weight were the main study outcomes. Infant length and head circumference, preterm birth, and low birth weight were secondary outcomes. RESULTS: Eighty-three percent of subjects completed the study (291 of 350 enrolled). No subject was discontinued for an adverse event. After controlling for important predefined risk factors and confounding variables, gestation increased by 6.0 +/- 2.3 days (P =.009) in the higher docosahexaenoic acid group. Birth weight, length, and head circumference increased, but did not reach statistical significance (P =.06-.18), although the increases could be clinically important indications of enhanced intrauterine growth. No safety concerns were raised by the study. CONCLUSION: Duration of gestation increased significantly when docosahexaenoic acid intake was increased during the last trimester of pregnancy. The increase in gestation was similar to that reported for interventions with much larger amounts of n-3 long chain polyunsaturated fatty acids.

Adolescent↗

PubMedDate not supplied

Maternal DHA and the development of attention in infancy and toddlerhood.

Infants were followed longitudinally to document the relationship between docosahexaenoic acid (DHA) levels and the development of attention. Erythrocyte (red-blood cell; RBC) phospholipid DHA (percentage of total fatty acids) was measured from infants and mothers at delivery. Infants were assessed in infant-control habituation at 4, 6, and 8 months augmented with psychophysiological measures, and on free-play attention and distractibility paradigms at 12 and 18 months. Infants whose mothers had high DHA at birth showed an accelerated decline in looking over the 1st year and increases in examining during single-object exploration and less distractibility in the 2nd year. These findings are consistent with evidence suggesting a link between DHA and cognitive development in infancy.

Arachidonic Acid↗