Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat.

Schmidt, Adam; Waldow, Kelly J.; Grove, William M.; Salinas, Juan A.; Georgieff, Michael

doi:10.1037/0735-7044.121.3.475

Cited by 68 publications

(104 citation statements)

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“…Although such data remain to be characterized in IDA rats, the changes in expression level might reflect the state of functional demands. Thus, it is possible that IDA-in- duced upregulation of RhoA and Rac1 at P7 reflects a compensation for a deficit in GTPases activity due to lower energy (GTP/ATP) availability in IDA rats [15] , while the changes at P65 may reflect reduced activity-dependent gene regulation [11,14,36] . The signaling and structural anomalies may account for the impaired electrophysiology (e.g.…”

Section: Discussionmentioning

confidence: 99%

Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus

Brunette¹,

et al. 2010

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The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.

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Section: Discussionmentioning

confidence: 99%

Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus

Brunette¹,

et al. 2010

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“…Animal data suggest that during early postnatal development, increases in Hip ferritin iron are necessary for normal cognitive function and memory (Carlson et al, 2009;Georgieff, 2008;Schmidt et al, 2007;Shoham and Youdim, 2002;Siddappa et al, 2004) and that early deficits can have long-lasting detrimental effects on cognition even when corrected through supplementation (Schmidt et al, 2007). Differentiating oligodendrocytes have very high iron requirements and may have a critical role in brain iron uptake (reviewed in Bartzokis et al, 2007a;Bartzokis et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Bartzokis

Tingus

et al. 2011

Neuropsychopharmacol

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Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON + ) vs noncarrier (IRONÀ) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON + vs IRONÀ status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r ¼ À0.50, p ¼ 0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRONÀ group (r ¼ À0.49, p ¼ 0.005) but not in the IRON + group. Between-group interactions (p ¼ 0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

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“…These results reveal that the imposition of the deficient diet up to 32 days continued to reduce the iron stores in the organism along the period evaluated, reducing Ht and Hb. However, the other components of the diet were adequate, a fact that may have provided the body weight gain, although the animals require iron for cell metabolism and growth and for the adequate development of body tissues (Schmidt et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Iron is a necessary component for red blood cell formation and for cell metabolism (Schmidt et al, 2007). Its deficiency may cause a reduction in the amount of serum iron (Cunha, van Ravenzwaay, Mellert & Kaufmann, 2008) and in hematocrit and liver iron stores (Bourque, Iqbal, Reynolds, Adams & Nakatsu, 2008), components whose deficiency may impair tissue growth and consequently reduce the body weight of individuals receiving iron-poor diets (Eseh & Zimmerberg, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Iron deficiency may alter metabolism, neurotransmission and glial integrity and may also increase the myelination time of the nervous system (Schmidt, Waldow, Grove, Salinas, & Georgieff, 2007) and reduce the magnitude of the acoustic startle response (Unger et al, 2006). However, the effects of protein-or iron-deficient diets on the myelin layer that envelops the specific neurons of the brainstem have not been reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Auditory evoked potential in handled and non-handled iron-deficient rats.

Rocinholi¹,

Lachat²,

Oliveira³

2008

Psychology & Neuroscience

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Iron deficiency alters metabolism, neurotransmission, glial integrity and the cortical myelin layer, besides increasing myelinization time. Environmental stimulation (handling) improves morphological, biochemical, electrophysiological and behavioral aspects of both well-nourished and malnourished animals. The objective of the present study was to determine the effects of an irondeficient diet and of handling on the brainstem auditory evoked potential (BAEP) of rats during development. Ninety-six male rats were divided since birth into Well-nourished (W, 35 mg iron/kg) and Anemic (A, 4 mg iron/kg) groups, and subdivided into Handling (H) and No Handling (NH). Body weight, hemoglobin (Hb), hematocrit (Ht), latencies of waves I, II, III IV, I-IV interpeak interval, and response threshold to auditory stimuli were evaluated at 18, 22, and 32 days. W animals presented higher Hb and Ht levels than A animals at 18, 22 and 32 days. The animals presented longer latencies of waves I, II, III and IV and I-IV interpeak interval of BAEP at 18 than at 22 and 32 days, and AH18 rats presented longer latencies of waves I and II than AH22 and AH32 rats, and longer wave I latency than WH18 animals. Iron deficiency increased the latencies of BAEP waves, suggesting damage to the myelin layer, especially during the early development, and the effects of handling were more evident along time in anemic animals.

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Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat.

Cited by 68 publications

References 68 publications

Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus

Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Auditory evoked potential in handled and non-handled iron-deficient rats.

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