Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats

Grecksch, Gisela; Rüthrich, H; Höllt, Volker; Becker, Axel

doi:10.1016/j.psyneuen.2009.07.004

Cited by 58 publications

(41 citation statements)

References 30 publications

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“…There is growing evidence that low vitamin D levels adversely impact on brain development [52]. In mice, it has been suggested that changes in brain development induced by prenatal vitamin D deficiency lead to specific functional alterations in hippocampal synaptic plasticity [53]. Also in humans, maternal vitamin D insufficiency has been associated with childhood rickets and longer term problems including schizophrenia [54].…”

Section: Discussionmentioning

confidence: 99%

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation

et al. 2010

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BackgroundMany natural phenomena are directly or indirectly related to latitude. Living at different latitudes, indeed, has its consequences with being exposed to different climates, diets, light/dark cycles, etc. In humans, one of the best known examples of genetic traits following a latitudinal gradient is skin pigmentation. Nevertheless, also several diseases show latitudinal clinals such as hypertension, cancer, dismetabolic conditions, schizophrenia, Parkinson's disease and many more.ResultsWe investigated, for the first time on a wide genomic scale, the latitude-driven adaptation phenomena. In particular, we selected a set of genes showing signs of latitude-dependent population differentiation. The biological characterization of these genes showed enrichment for neural-related processes. In light of this, we investigated whether genes associated to neuropsychiatric diseases were enriched by Latitude-Related Genes (LRGs). We found a strong enrichment of LRGs in the set of genes associated to schizophrenia. In an attempt to try to explain this possible link between latitude and schizophrenia, we investigated their associations with vitamin D. We found in a set of vitamin D related genes a significant enrichment of both LRGs and of genes involved in schizophrenia.ConclusionsOur results suggest a latitude-driven adaptation for both schizophrenia and vitamin D related genes. In addition we confirm, at a molecular level, the link between schizophrenia and vitamin D. Finally, we discuss a model in which schizophrenia is, at least partly, a maladaptive by-product of latitude dependent adaptive changes in vitamin D metabolism.

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Section: Discussionmentioning

confidence: 99%

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation

et al. 2010

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“…They showed that both risperidone and haloperidol normalized long-term potentiation in DVD-deficient offspring. 45 Most recently, this group showed that haloperidol restored adult neurogenesis deficits in this model. 46 Studies in other laboratories have also shown that haloperidol appeared to preferentially normalize N -methyl--aspartate antagonist induced hyperlocomotion in DVD-deficient rats compared with that induced in controls.…”

Section: The Dvd-deficiency and Mia Developmental Animal Models Of Scmentioning

confidence: 94%

Schizophrenia: do all roads lead to dopamine or is this where they start? Evidence from two epidemiologically informed developmental rodent models

2012

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The idea that there is some sort of abnormality in dopamine (DA) signalling is one of the more enduring hypotheses in schizophrenia research. Opinion leaders have published recent perspectives on the aetiology of this disorder with provocative titles such as ‘Risk factors for schizophrenia—all roads lead to dopamine' or ‘The dopamine hypothesis of schizophrenia—the final common pathway'. Perhaps, the other most enduring idea about schizophrenia is that it is a neurodevelopmental disorder. Those of us that model schizophrenia developmental risk-factor epidemiology in animals in an attempt to understand how this may translate to abnormal brain function have consistently shown that as adults these animals display behavioural, cognitive and pharmacological abnormalities consistent with aberrant DA signalling. The burning question remains how can in utero exposure to specific (environmental) insults induce persistent abnormalities in DA signalling in the adult? In this review, we summarize convergent evidence from two well-described developmental animal models, namely maternal immune activation and developmental vitamin D deficiency that begin to address this question. The adult offspring resulting from these two models consistently reveal locomotor abnormalities in response to DA-releasing or -blocking drugs. Additionally, as adults these animals have DA-related attentional and/or sensorimotor gating deficits. These findings are consistent with many other developmental animal models. However, the authors of this perspective have recently refocused their attention on very early aspects of DA ontogeny and describe reductions in genes that induce or specify dopaminergic phenotype in the embryonic brain and early changes in DA turnover suggesting that the origins of these behavioural abnormalities in adults may be traced to early alterations in DA ontogeny. Whether the convergent findings from these two models can be extended to other developmental animal models for this disease is at present unknown as such early brain alterations are rarely examined. Although it is premature to conclude that such mechanisms could be operating in other developmental animal models for schizophrenia, our convergent data have led us to propose that rather than all roads leading to DA, perhaps, this may be where they start.

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“…Physiological concentrations of vitamin D3 have been shown to delay cell proliferation and induce cell differentiation of embryonic hippocampal cells in mice [27]. Long-lasting effects of transient gestational vitamin D deficiency include decreased expression of many genes involved in neuronal structures and neurotransmission [28], a disrupted balance between neuronal stem cell proliferation and programmed cell death in offspring [3] and abnormal brain development leading to morphological, cellular, and molecular changes in the brain [4], including the hippocampus [5], and altered behaviors in the offspring [5]. Many of the effects of transient vitamin D deficiency during early development include changes that are relevant to autism, including enlarged lateral ventricles and dysregulation of numerous brain proteins within biological pathways implicated in autism, including redox balance, calcium homeostasis, neurotransmission, and synaptic plasticity [29].…”

Section: Discussionmentioning

confidence: 99%

“…The biologic plausibility for a link between vitamin D and autism is ample, as previously reviewed [1,2]. Animal studies show long-lasting neurodevelopmental effects of transient vitamin D deficiency during gestation leading to autism-relevant structural and functional changes in the brain and behaviors of the offspring [3–5]. Gene variants within the vitamin D pathway can determine uptake and utilization of vitamin D. Genetic susceptibility to inefficient vitamin D uptake and metabolism has yet to be explored in relation to autism.…”

Section: Introductionmentioning

confidence: 99%

Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study

Schmidt

Hansen

Hartiala

et al. 2015

Early Human Development

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Background Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined associations between autism spectrum disorder (ASD) and common, functional polymorphisms in vitamin D pathways. Methods Children aged 24–60 months enrolled from 2003 to 2009 in the population-based CHARGE case–control study were evaluated clinically and confirmed to have ASD (n = 474) or typical development (TD, n = 281). Maternal, paternal, and child DNA samples for 384 (81%) families of children with ASD and 234 (83%) families of TD children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor (VDR) gene, and CYP27B1 rs4646536, GC rs4588, and CYP2R1 rs10741657. Case–control logistic regression, family-based log-linear, and hybrid log-linear analyses were conducted to produce risk estimates and 95% confidence intervals (CI) for each allelic variant. Results Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case–control analysis (odds ratio [OR] [CI]: 6.3 [1.9–20.7]) and there was a trend towards increased risk associated with VDR BsmI (OR [CI]: 4.7 [1.6–13.4]). Log-linear triad analyses detected parental imprinting, with greater effects of paternally-derived VDR alleles. Child GC AA-genotype/A-allele was associated with ASD in log-linear and ETDT analyses. A significant association between decreased ASD risk and child CYP2R1 AA-genotype was found in hybrid log-linear analysis. There were limitations of low statistical power for less common alleles due to missing paternal genotypes. Conclusions This study provides preliminary evidence that paternal and child vitamin D metabolism could play a role in the etiology of ASD; further research in larger study populations is warranted.

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Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats

Cited by 58 publications

References 30 publications

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation

Schizophrenia: do all roads lead to dopamine or is this where they start? Evidence from two epidemiologically informed developmental rodent models

Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study

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