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Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

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ABSTRACT

Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders.

No MeSH data available.


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Neonatal maternal separation (NMS) decreases carotid sinus nerve (CSN) response to hypoxia in female rats. (A) Original recordings comparing CSN activity from ex vivo preparations of perfused carotid body/CSN from control and NMS females under hyperoxia (FiO2 = 0.95), hypoxia (FiO2 = 0.0) and hyperoxia after hypoxia (recovery). (B) Comparison of the mean carotid sinus nerve activity (imp/sec) over the course of the hypoxic protocol between carotid bodies from control (open squares; n = 5) and NMS rats (black squares; n = 5). Hypoxia begins at T = 0 and is maintained until T = 500 s (end of plateau phase), followed by hyperoxic recovery; each data point represents the mean value on a second by second basis. (C) Histograms comparing mean CSN activity for each specific experimental condition between control (white bars; n = 5) and NMS (black bars; n = 5) female rats. Data are reported as means ± SD. *Indicates a value statistically different from control at p ≤ 0.05.
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Figure 2: Neonatal maternal separation (NMS) decreases carotid sinus nerve (CSN) response to hypoxia in female rats. (A) Original recordings comparing CSN activity from ex vivo preparations of perfused carotid body/CSN from control and NMS females under hyperoxia (FiO2 = 0.95), hypoxia (FiO2 = 0.0) and hyperoxia after hypoxia (recovery). (B) Comparison of the mean carotid sinus nerve activity (imp/sec) over the course of the hypoxic protocol between carotid bodies from control (open squares; n = 5) and NMS rats (black squares; n = 5). Hypoxia begins at T = 0 and is maintained until T = 500 s (end of plateau phase), followed by hyperoxic recovery; each data point represents the mean value on a second by second basis. (C) Histograms comparing mean CSN activity for each specific experimental condition between control (white bars; n = 5) and NMS (black bars; n = 5) female rats. Data are reported as means ± SD. *Indicates a value statistically different from control at p ≤ 0.05.

Mentions: Following baseline recording, the perfusate delivered to the chamber was changed from hyperoxia to hypoxia. Following a brief delay (~90 s), CSN activity augmented in all experimental groups [F(2, 44) = 157.9; p < 0.0001; Figures 1, 2] and a plateau was observed within 3 min. During this new “steady state,” the mean CSN activity observed in NMS males was higher than controls (Figure 1). These responses represent increases of 351 ± 136% and 521 ± 151% for controls and NMS, respectively; thus, the CSN response of NMS males was 1.5-fold greater than controls. Following hypoxia, CSN activity progressively returned toward baseline levels in both groups.


Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats
Neonatal maternal separation (NMS) decreases carotid sinus nerve (CSN) response to hypoxia in female rats. (A) Original recordings comparing CSN activity from ex vivo preparations of perfused carotid body/CSN from control and NMS females under hyperoxia (FiO2 = 0.95), hypoxia (FiO2 = 0.0) and hyperoxia after hypoxia (recovery). (B) Comparison of the mean carotid sinus nerve activity (imp/sec) over the course of the hypoxic protocol between carotid bodies from control (open squares; n = 5) and NMS rats (black squares; n = 5). Hypoxia begins at T = 0 and is maintained until T = 500 s (end of plateau phase), followed by hyperoxic recovery; each data point represents the mean value on a second by second basis. (C) Histograms comparing mean CSN activity for each specific experimental condition between control (white bars; n = 5) and NMS (black bars; n = 5) female rats. Data are reported as means ± SD. *Indicates a value statistically different from control at p ≤ 0.05.
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Figure 2: Neonatal maternal separation (NMS) decreases carotid sinus nerve (CSN) response to hypoxia in female rats. (A) Original recordings comparing CSN activity from ex vivo preparations of perfused carotid body/CSN from control and NMS females under hyperoxia (FiO2 = 0.95), hypoxia (FiO2 = 0.0) and hyperoxia after hypoxia (recovery). (B) Comparison of the mean carotid sinus nerve activity (imp/sec) over the course of the hypoxic protocol between carotid bodies from control (open squares; n = 5) and NMS rats (black squares; n = 5). Hypoxia begins at T = 0 and is maintained until T = 500 s (end of plateau phase), followed by hyperoxic recovery; each data point represents the mean value on a second by second basis. (C) Histograms comparing mean CSN activity for each specific experimental condition between control (white bars; n = 5) and NMS (black bars; n = 5) female rats. Data are reported as means ± SD. *Indicates a value statistically different from control at p ≤ 0.05.
Mentions: Following baseline recording, the perfusate delivered to the chamber was changed from hyperoxia to hypoxia. Following a brief delay (~90 s), CSN activity augmented in all experimental groups [F(2, 44) = 157.9; p < 0.0001; Figures 1, 2] and a plateau was observed within 3 min. During this new “steady state,” the mean CSN activity observed in NMS males was higher than controls (Figure 1). These responses represent increases of 351 ± 136% and 521 ± 151% for controls and NMS, respectively; thus, the CSN response of NMS males was 1.5-fold greater than controls. Following hypoxia, CSN activity progressively returned toward baseline levels in both groups.

View Article: PubMed Central - PubMed

ABSTRACT

Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders.

No MeSH data available.


Related in: MedlinePlus