Aspartic acid in the arcuate nucleus attenuates the depressive effects of naloxone on ventilation

Schlenker, Evelyn H.

doi:10.1016/s0034-5687(98)00081-4

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…*P Ͻ 0.05 for differences between A y and control mice. (10,13,42,48) and 2) hypothalamic neural projections can influence central hypercapnic ventilatory responsiveness (40,41), it is attractive to propose that the effects of leptin on respiratory control are also dependent on hypothalamic pathways. However, the blockade of MC4 receptors by AGRP in A y mice is not limited to hypothalamic regions.…”

Section: Discussionmentioning

confidence: 99%

Impact of interrupted leptin pathways on ventilatory control

Polotsky¹,

Smaldone²,

Scharf³

et al. 2004

Journal of Applied Physiology

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Leptin deficiency in ob/ob mice produces marked depression of the hypercapnic ventilatory response, particularly during sleep. We now extend our previous findings to determine whether 1) leptin deficiency affects the hypoxic ventilatory response and 2) blockade of the downstream excitatory actions of leptin on melanocortin 4 receptors or inhibitory actions on neuropeptide Y (NPY) pathways has an impact on hypercapnic and hypoxic sensitivity. We have found that leptin-deficient ob/ob mice have the same hypoxic ventilatory response as weight-matched wild-type obese mice. There were no differences in the hypoxic sensitivity between agouti yellow mice and weight-matched controls, or NPY-deficient mice and wild-type littermates. Agouti yellow mice, with blocked melanocortin pathways, exhibited a significant depression of the hypercapnic sensitivity compared with weight-matched wild-type controls during non-rapid eye movement sleep (5.8 +/- 0.7 vs. 8.9 +/- 0.7 ml x min(-1) x %CO(2)(-1), P < 0.01), but not during wakefulness. NPY-deficient transgenic mice exhibited a small increase in the hypercapnic ventilatory response compared with wild-type littermates, but this was only present during wakefulness. We conclude that interruption of leptin pathways does not affect hypoxic sensitivity during sleep and wakefulness but that melanocortin 4 blockade is associated with depressed hypercapnic sensitivity in non-rapid eye movement sleep.

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Section: Discussionmentioning

confidence: 99%

Impact of interrupted leptin pathways on ventilatory control

Polotsky¹,

Smaldone²,

Scharf³

et al. 2004

Journal of Applied Physiology

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“…Nonetheless, the driving mechanisms of the hypothalamic functions are far to be completely understood, and even though there is evidence that hypothalamic activity is deeply influenced by the serotonergic tone [Chalmers et al, 1988;Reichlin, 1988;Minson et al, 1990;Recio et al, 1996;Schuhler et al, 1999;Lowry, 2002;Serretti et al, 2004; Aisa et al, 2007;Marcos et al, 2008], and the efficacy of antidepressant drugs with a serotonergic activity in severe forms of depressive episodes has been widely demonstrated, it is reasonable to assess that serotonin receptors activated probably witness a first step event, whilst the antidepressant effect, or the depressive molecular mechanism itself, probably lies elsewhere within the molecular changes that follow the serotonergic activations. For example, it has been proposed that cannabinoid receptor 1 in hypothalamus and hippocampus may be the pivotal actor of the antidepressant properties of desipramine [Hill et al, 2006], but many other evidence based hypotheses involving diverse systems have been put forward as well [Alvarez and Banzan, 1992;Schlenker, 1998;Holsboer, 1999;Carrasco et al, 2004;Huang et al, 2004;Malkesman et al, 2007]. Further research in this field is mandatory before a complete depict is achieved.…”

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confidence: 99%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

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HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

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“…There is, in fact, ample evidence of a relationship between the hypothalamus and respiratory drive. In mammalian models, neurons of the paraventricular hypothalamus have been shown to project to respiratory centers in the medulla and spinal cord (17), and show changes in cellular activity that correlate with breathing patterns (18). Furthermore, in rats, neurons of the paraventricular hypothalamus modulate respiratory rhythm when activated directly via microinjection of neurotransmitters (19,20).…”

Section: Discussionmentioning

confidence: 99%