Pre- and Post-natal High Fat Feeding Differentially Affects the Structure and Integrity of the Neurovascular Unit of 16-Month Old Male and Female Mice

Contu, Laura; Nizari, Shereen; Heath, Christopher; Hawkes, Cheryl A.

doi:10.3389/fnins.2019.01045

Cited by 16 publications

(8 citation statements)

References 90 publications

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“…Further, the NVU is responsible for the maintenance of a highly selective blood-brain barrier (BBB) and cerebral homeostasis, as well as the control of cerebral blood flow (CBF) (79). The impact of maternal diet on the NVU, modulating integrity of cerebral blood vessels and closure of the neural tube, has been established (15,16,(80)(81)(82). Our study adds to these investigations by assessing the hemodynamic response of blood flow within the posterior cerebral artery (PCA) in both young and aged offspring.…”

Section: Discussionmentioning

confidence: 99%

The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke

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Kang

et al. 2022

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A maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. One-carbon metabolism plays an important role in the closure of the neural tube of the developing embryo; however, the impact of maternal one-carbon dietary deficiencies on offspring neurological function later in life remains relatively unknown. Stroke is one of the leading causes of death globally, and its prevalence is expected to increase in younger age groups as the incidence of various risk factors for stroke increases. The aim of our study was to determine the impact of maternal nutritional deficiencies on cerebral blood flow and peripheral hemodynamics after ischemic stroke in adult offspring. In this study, adult female C57BL/6J mice were placed on either control (CD), choline (ChDD) or folic acid (FADD) deficient diets for four weeks to deplete stores prior to mating and maintained on the assigned diet during pregnancy and lactation. Female offspring were weaned and transitioned to a CD for the duration of the study. Ischemic stroke was induced in the sensorimotor cortex of 2- and 10-month-old female offspring using the photothrombosis model. Six weeks after induction of stroke, cerebral and peripheral blood flow was measured using the Vevo2100 Pulse Wave Doppler tracing modality. Our data showed that 3.5-month-old female offspring from a ChDD mothers had reduced blood flow in the posterior cerebral artery compared to CD mice; this effect disappeared in older offspring. In 11.5-month-old females we observed changes in peripheral hemodynamics, but not in young animals. Our findings suggest that a maternal dietary deficiency in choline results in reduced cerebral blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuro-programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.

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Section: Discussionmentioning

confidence: 99%

The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke

Pull

Folk

Kang

et al. 2022

Preprint

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“…Frozen brain tissues (n = 7/group) were processed by gel electrophoresis as previously described [ 28 ]. Membranes were incubated with primary antibodies against cannabinoid receptor 1 (CB1, 1:1000, Abcam, Cambridge, UK), mu opioid receptor 1 (mOR1, 1:1000, Merck) and dopamine transporter (DAT, 1:750, Merck).…”

Section: Methodsmentioning

confidence: 99%

“…Brains were processed for immunohistochemistry (n = 5/group) as described previously [ 28 ]. Brain sections were washed in 0.01 M PBS, blocked with a mixture of 7.5% normal goat serum + 7.5% normal donkey serum and then incubated overnight at 4 ºC with anti-GFAP (1:1500; Abcam), anti-CB1 (1:1000, Abcam) and anti-NeuN (1:750, Abcam).…”

Section: Methodsmentioning

confidence: 99%

α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression

Hawkes

Heath

Sharp

et al. 2022

acta neuropathol commun

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Abstractα-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems.

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“…Dams were kept on the diet during gestation and lactation. Macro minerals, vitamins, and amino acid composition was matched between diets, as previously described [ 43 ]. Studs were maintained on the C diet until breeding.…”

Section: Methodsmentioning

confidence: 99%

Appetitive Motivation and Associated Neurobiology Change Differentially across the Life Course of Mouse Offspring Exposed to Peri- and Postnatal High Fat Feeding

2022

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Alterations in neural pathways that regulate appetitive motivation may contribute to increased obesity risk in offspring born to mothers fed a high fat (HF) diet. However, current findings on the impact of maternal obesity on motivation in offspring are inconclusive, and there is no information about the long-lasting effects in aged animals. This study examined the longitudinal effect of perinatal and chronic postnatal HF intake on appetitive motivation in young and aged offspring. Female C57Bl/6 were fed either a control (C) or HF diet before mating through to lactation. At weaning, offspring were maintained on the C or HF diet, generating the following four diet groups: C/C, C/HF, HF/C, and HF/HF based on the pre/post weaning diet. At 6 months, motivation was higher in HF/C females, but lower in male and female C/HF and HF/HF mice. By 12 months, this difference was lost, as C-fed animals became less motivated, while motivation increased in HF-fed mice. The mRNA levels of dopamine receptor 1 and 2 increased with age, while cannabinoid receptor 1 and μ-opioid receptor expression remained stable or decreased in mesolimbic and mesocortical dopaminergic pathways. Results from this study suggest that perinatal and chronic postnatal HF feeding produced opposite effects on appetitive motivation in young adult offspring mice, which was also reflected in the shift in motivation over time. These results have significant implications for patterns of hedonic eating across the life course and the relative risk of obesity at different time points.

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Pre- and Post-natal High Fat Feeding Differentially Affects the Structure and Integrity of the Neurovascular Unit of 16-Month Old Male and Female Mice

Cited by 16 publications

References 90 publications

The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke

The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke

α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression

Appetitive Motivation and Associated Neurobiology Change Differentially across the Life Course of Mouse Offspring Exposed to Peri- and Postnatal High Fat Feeding

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