High Altitude Hypoxia and Adrenal Development in the Rat: Enzymes for Biogenic Amines

Vaccari, Andrea; Cimino, Jonathan; Brotman, Steven; Timiras, P.S.

doi:10.1007/978-3-642-66981-1_44

Cited by 6 publications

(5 citation statements)

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“…While most of these data are either from male rats (PriouxGuyonneau et al, 1982) or not analyzed by gender (Ray et al, 2011;Vaccari et al, 1978), and vary with period of hypoxia exposure, data from our preliminary studies imply that both female and male rats exhibit lower levels of serotonin but unchanged dopamine levels in the striatum after a week of housing at 20,000 ft vs. at local conditions of 4,500 ft (Kanekar, unpublished observations). If hypobaric hypoxia causes an imbalance in brain monoamines in humans residing at altitude, this could contribute to the increased depression rates seen in populations at altitude.…”

Section: Discussionmentioning

confidence: 79%

“…Chronic exposure to hypobaric hypoxia (2 weeks at 25,000 ft) significantly reduced serotonin in frontal cortex and brainstem in both male and female rats (Ray et al, 2011), while acute hypoxia (24 h at 22,960 ft) depleted serotonin in the male rat striatum and hypothalamus by 34% (Prioux-Guyonneau et al, 1982). Tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, requires molecular oxygen for its activity (Fitzpatrick, 1999), and is extremely vulnerable to hypoxia (Davis et al, 1973;Vaccari et al, 1978), potentially lowering brain serotonin synthesis in hypoxia. Hypoxia alters activity of both synthetic and catabolic enzymes in the noradrenergic pathway (Gozal et al, 2005;Vaccari et al, 1978), potentially changing brain dopamine and norepinephrine levels as well (Kumar, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, requires molecular oxygen for its activity (Fitzpatrick, 1999), and is extremely vulnerable to hypoxia (Davis et al, 1973;Vaccari et al, 1978), potentially lowering brain serotonin synthesis in hypoxia. Hypoxia alters activity of both synthetic and catabolic enzymes in the noradrenergic pathway (Gozal et al, 2005;Vaccari et al, 1978), potentially changing brain dopamine and norepinephrine levels as well (Kumar, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Kanekar

Bogdanova

Olson

et al. 2015

High Altitude Medicine & Biology

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Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52-60, 2015-Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Kanekar

Bogdanova

Olson

et al. 2015

High Altitude Medicine & Biology

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“…Although such alterations often do not become apparent until postnatal life, it has been suggested that these disturbances may have their origin in subtle changes which occur during the foetal period (Petropoulos «fe Timiras,19 Ab). The hypothalamo-pituitaryadrenal system, for example, shows pronounced functional disturbances during postnatal growth at high altitude : the adrenal gland hypertrophies within the first week after birth and is hyperactive from early postnatal life into adulthood (Vaccari, Cimino, Brotman & Timiras, 1978).…”

Section: Introductionmentioning

confidence: 99%

Alterations in Adrenal Growth and Corticosteroid Content in Foetal and Neonatal Rats Developing at High Altitude

Garvey¹,

Akana²,

Weisman³

et al. 1979

Journal of Endocrinology

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To study the effects of chronic maternal hypoxia on the growth and functional development of foetal and neonatal adrenal glands, Long-Evans rats were acclimatized to high altitude (3800 m) before mating and were maintained at this height throughout gestation. The body growth of the progeny at high altitude was essentially normal during the perinatal period, but adrenal weight and adrenocortical function showed marked differences from those of control rats maintained at sea level. The adrenal glands were larger in foetuses but smaller in neonates, compared with the adrenal glands of control animals maintained at sea level. Differences in the protein content of the adrenal glands between the two groups paralleled differences in adrenal weight. The concentration and content of corticosterone in the adrenal glands of both foetuses and neonates kept at high altitude were markedly lower than values in animals kept at sea level. The lower adrenal corticosterone content was not reflected in the concentration of the hormone in the peripheral plasma, since this was essentially the same at high altitude and at sea level in both mothers and perinatal animals. The reduction in the adrenal corticosterone content was accompanied by and may have resulted from, a reduction in the concentration of cytochrome P-450 in the adrenal tissue of foetuses maintained at high altitude. Possible explanations for the dichotomous results are discussed.

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“…6 It is well known that hypobaric hypoxia induces a stress, resulting in an increased cerebral 5,7 and cardiac 8 aminergic turnover and in a modification of the adrenal metabolism. 9, 10 We then compared the effects of apomorphine in normal and adrenalectomized rats to see SUMMARY Previous data have established that postsynaptic stimulation of central dopaminergic receptors was mainly involved in the protective action of apomorphine against the comportmental consequences of hypobaric hypoxia in rats: disturbances in a conditioned avoidance response. We confirm this notion by showing that domperidone (a peripheral dopaminergic blocking agent) does not antagonize the protective effect of apomorphine.…”

mentioning

confidence: 99%

Interference between central dopaminergic stimulation, and adrenal secretion in normoxic or hypobaric hypoxic rats.

Saligaut¹,

Moore²,

Chretien³

et al. 1982

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Previous data have established that postsynaptic stimulation of central dopaminergic receptors was mainly involved in the protective action of apomorphine against the comportmental consequences of hypobaric hypoxia in rats: disturbances in a conditioned avoidance response. We confirm this notion showing that domperidone (a peripheral dopaminergic blocking agent) does not antagonize the protective effect of apomorphine. Furthermore, we establish that the action of apomorphine is at least partially mediated by adrenal glands since it is no longer seen in adrenalectomized rats. In normal rats, apomorphine enhances the corticosterone increase which is observed during hypobaric hypoxia and decreases the hypoxia-induced elevation of the adrenaline level. It is therefore concluded that the anti-hypoxic activity of apomorphine is probably mediated by a centrally mediated dopaminergic modification of the adrenal response to hypobaric hypoxia.

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High Altitude Hypoxia and Adrenal Development in the Rat: Enzymes for Biogenic Amines

Cited by 6 publications

References 14 publications

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Alterations in Adrenal Growth and Corticosteroid Content in Foetal and Neonatal Rats Developing at High Altitude

Interference between central dopaminergic stimulation, and adrenal secretion in normoxic or hypobaric hypoxic rats.

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