ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour

Bracke, Alexander; Schäfer, Simon; Halbach, Viola von Bohlen und; Klempin, Friederike; Kiens, Bente; Bracke, Katharina; Staar, Doreen; Brandt, Jens van den; Harzsch, Steffen; Bäder, Michael; Wenzel, Ulrich; Peters, Jörg; Halbach, Oliver von Bohlen und

doi:10.1007/s00429-018-1633-1

Cited by 10 publications

(14 citation statements)

References 58 publications

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“…As a core protein involved in neurogenic Wnt signaling pathways, Atp6ap2 is critical for proliferating adult neural stem cells and differentiating neuroblasts, essential in early brain development, adult hippocampal neurogenesis, and in cognitive functions. Lack of Atp6ap2 leads to cognitive impairment and neurodegeneration, and mutations of Atp6ap2 in humans are associated with intellectual disability [ 47 , 48 ]. Postsynaptic density proteins (PSD) play a critical role in regulating the density and activity of glutamate receptors.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine hyperglycemia impairs memory across two generations

et al. 2021

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Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM.

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Section: Discussionmentioning

confidence: 99%

Intrauterine hyperglycemia impairs memory across two generations

et al. 2021

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“…Analysis was conducted within the dentate gyrus (DG) of the hippocampus using an Axioplan 2 imaging microscope (Zeiss, Germany). Immunopositive cells were counted in each animal analyzed (PH3: wt n = 9; ob/ob n = 10; DCX: wt n = 13; ob/ob n = 9; Casp3: wt n = 12; ob/ob n = 8) and the estimated total cell count for each immunostaining was corrected as described previously 9 using the Linderstrom-Lang/Abercrombie equation…”

Section: Methodsmentioning

confidence: 99%

“…Brain volume was determined using microvolumetry (µ-VM) as described previously. 9 In brief, a 5-mL syringe was used as a sample container with a 1-mL syringe attached as a measurement device. 3 mL of 4% paraformaldehyde (PFA) were used as the fluid in the sample container in which the mouse brain was placed.…”

Section: Microvolumetrymentioning

confidence: 99%

Obesity Impairs Mobility and Adult Hippocampal Neurogenesis

et al. 2019

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Currently, it is controversially discussed whether a relationship between obesity and cognition exists. We here analyzed a mouse model of obesity (leptin-deficient mice) to study the effects of obesity on the morphology of the hippocampus (a brain structure involved in mechanisms related to learning and memory) and on behavior. Mice aged 4 to 6 months were analyzed. At this age, the obese mice have nearly double the body weight as controls, but display smaller brains (brain volume is about 10% smaller) as control animals of the same age. Adult hippocampal neurogenesis, a process that is linked to learning and memory, might be disturbed in the obese mice and contribute to the smaller brain volume. Adult hippocampal neurogenesis was examined using specific markers for cell proliferation (phosphohistone H3), neuronal differentiation (doublecortin), and apoptosis (caspase 3). The number of phosphohistone H3 and doublecortin-positive cells was markedly reduced in leptin-deficient mice, but not the number of apoptotic cells, indicating that adult hippocampal neurogenesis on the level of cell proliferation was affected. In addition, dendritic spine densities of pyramidal neurons in the hippocampal area CA1 were analyzed using Golgi impregnation. However, no significant change in dendritic spine densities was noted in the obese mice. Moreover, the performance of the mice was analyzed in the open field as well as in the Morris water maze. In the open field test, obese mice showed reduced locomotor activity, but in the Morris water maze they showed similar performance compared with control animals.

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“…Brain volume was determined by using microvolumetry (µ-VM) as described previously (26). In brief, a 5 ml syringe was used as sample container with a 1 ml syringe attached as measurement device.…”

Section: Microvolumetrymentioning

confidence: 99%

Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice

Bracke¹,

Domańska

Bracke³

et al. 2019

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Background: Obesity has become a severe problem among the world´s population with clearly increasing prevalence over the last decades. Because obesity is associated with several comorbidities (e.g. hypertension or cancer) it constitutes an increasing burden for the health care system. Correlations between obesity and cognition have been studied in humans with ambivalent results. Here, we studied the effects of obesity on hippocampus dependent learning and memory and cell morphology in a mouse model of obesity. Methods:The body mass of male and female Lep +/+ (wt) and Lep ob/ob (ob/ob) animals with access to food and water ad libitum was measured between postnatal day 60-200 and animals with clear adiposity (4-6 months) were further analyzed. Adult hippocampal neurogenesis in the dentate gyrus was examined using phosphohistone H3 as a marker for proliferation, doublecortin as a marker for differentiation and caspase3 as a marker for apoptosis. Moreover, the density of dendritic spines on apical and basal dendrites of pyramidal neurons of the cornu ammonis 1 (CA1) were analyzed using Golgi impregnation. In addition, mice were subjected to the open field and Morris water maze test in order to analyze locomotor activity and spatial learning. Results:The body weight of ob/ob mice nearly doubled during the first 120 postnatal days. Adult hippocampal neurogenesis was reduced in ob/ob mice due to reduced cell proliferation. Dendritic spine densities in the hippocampal area CA1 were not altered in ob/ob mice. Four to six months old ob/ob mice showed reduced locomotor activity in the open field test but similar performance in the Morris water maze compared to control mice. Conclusion:Our data show that alterations in adult neurogenesis in leptin-deficient mice are not associated with an impairment in spatial learning abilities. Moreover, ob/ob mice are inconspicuous in the Morris water maze and do not display altered spine densities in the hippocampus, suggesting that obesity does not have a severe impact upon hippocampal neuronal plasticity and spatial learning.

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ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour

Cited by 10 publications

References 58 publications

Intrauterine hyperglycemia impairs memory across two generations

Intrauterine hyperglycemia impairs memory across two generations

Obesity Impairs Mobility and Adult Hippocampal Neurogenesis

Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice

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