Dataset Information

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.

ABSTRACT:

Background

Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms.

Objectives

The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring.

Methods

Wistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1? (HIF-1?) expression was also evaluated in carotid bifurcation through a Western blotting assay.

Results

At 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (?91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (?86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of ?100% in HIF-1? protein density in carotid bifurcation compared with NP rats.

Conclusion

Sympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1?-dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation.

SUBMITTER: de Brito Alves JL

PROVIDER: S-EPMC6619683 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.

de Brito Alves José L JL Nogueira Viviane O VO Cavalcanti Neto Marinaldo P MP Leopoldino Andréia M AM Curti Carlos C Colombari Débora S A DS Colombari Eduardo E Wanderley Almir G AG Leandro Carol G CG Zoccal Daniel B DB Costa-Silva João H JH

The Journal of nutrition 20150218 5

<h4>Background</h4>Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms.<h4>Objectives</h4>The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring.<h4>Methods</h4>Wistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet durin ...[more]

PMID: 25934662

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Project description:Early life challenges resulting from maternal immune activation (MIA) may exert persistent effects on the offspring, including the development of psychiatric disorders, such as schizophrenia. Recent evidence has suggested that the adverse effects of MIA may be mediated by neuron-microglia crosstalk, particularly CX3CL1-CX3CR1 and CD200-CD200R dyads. Therefore, the present study assessed the behavioural parameters resembling schizophrenia-like symptoms in the adult male offspring of Sprague-Dawley rats that were exposed to MIA and to an additional acute lipopolysaccharide (LPS) challenge in adulthood, according to the "two-hit" hypothesis of schizophrenia. Simultaneously, we aimed to clarify the role of the CX3CL1-CX3CR1 and CD200-CD200R axes and microglial reactivity in the brains of adult offspring subjected to MIA and the "second hit" wit LPS. In the present study, MIA generated a range of behavioural changes in the adult male offspring, including increased exploratory activity and anxiety-like behaviours. The most intriguing finding was observed in the prepulse inhibition (PPI) test, where the deficit in the sensorimotor gating was age-dependent and present only in part of the rats. We were able to distinguish the occurrence of two groups: responsive and non-responsive (without the deficit). Concurrently, based on the results of the biochemical studies, MIA disrupted mainly the CD200-CD200R system, while the changes of the CX3CL1-CX3CR1 axis were less evident in the frontal cortex of adult non-responsive offspring. MIA markedly affected the immune regulators of the CD200-CD200R pathway as we observed an increase in cortical IL-6 release in the responsive group and IL-4 in the non-responsive offspring. Importantly, the "second hit" generated disturbances at the behavioural and biochemical levels mostly in the non-responsive adult animals. Those offspring were characterized both by disturbed PPI and "priming" microglia. Altogether, the exposure to MIA altered the immunomodulatory mechanisms, including the CD200-CD200R axis, in the brain and sensitized animals to subsequent immunological challenges, leading to the manifestation of schizophrenia-like alterations.

Dataset Information

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.

Background

Objectives

Methods

Results

Conclusion

Publications

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.

Similar Datasets

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