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It has been suggested that the MCHergic and hypocretinergic
It has been suggested that the MCHergic and hypocretinergic systems reciprocally regulates several physiological functions such as wakefulness and sleep [16]. It is likely that other functions, like mood, are also controlled in a reciprocally way by these systems. In this regards, FLX tended to decrease the MCH/hypocretin-1 concentration ratio (p=0.057). It is likely that FLX move the balance between the MCHergic and hypocretinergic neuronal activity, down-regulating the first in favor of the hypocretinergic side of the equation.
Finally, it is known that acute treatment with ketamine increases the antidepressant effect of FLX [25]. However, in our experiments, ketamine anesthesia as well as taps and freezing procedures lasted no more than 20min, a time that should not be enough to alter neither the peptides CSF concentrations nor the gene expression. In addition, this procedure was done both in control and experimental animals; hence we consider that ketamine did not modify the results.
Conclusions and future directions
New experiments are needed in order to confirm and dissect the effect of classical antidepressant on the MCHergic and hypocretinergic systems. A new series of experiments in animal models of depression (chronic mild stress, olfactory bulbectomy, etc.) are warranted [22]; we hypothesize that the effect of FLX should be even more pronounced in depressive individuals.
Acknowledgements
This study was supported by the “Proyecto de Cooperación Bilateral Uruguay- Brasil, Dicyt-CNPq”, ANII-FCE-1-2011-1-5997, Programa de Desarrollo de Ciencias Básicas (PEDECIBA), and Associação Fundo de Incentivo à Pesquisa (AFIP). VD’A is recipient of a research fellowship obtained from CNPq. We are grateful to MSc. Matias Cavelli for his technical assistance. No conflict of interest to declare.
Introduction
Hypoxic insults occurring during the perinatal period are among the leading causes of permanent phospholipase inhibitor dysfunction and remain a serious public health concern [1–3]. Most hypoxic insults typically occur in the setting of unambiguous clinical compromise, such as placental dysfunction, prolonged labor, or cardiorespiratory resuscitation [4,5]. However, other more insidious mechanisms, such as apnea of prematurity, which is a common occurrence in prematurely born infants [6–9], can induce repetitive hypoxic insults. Between 10% and 13% of all infants are born prematurely [10,11]. Apnea with concomitant hypoxic insults will afflict 78% of those born at 26–27 weeks gestation, 54% born at 30–31 weeks, and 7% born at 34–35 weeks [6].
Regardless of whether children who are born prematurely or at term, perinatal hypoxic insults are associated with diminished academic performance and other manifestations of executive dysfunction [12–16]. Perturbed function within neural networks subserving arousal and/or vigilance is also seen; infants with a history of apnea of prematurity require more intensive stimuli to be awakened from sleep [17]. Dampened autonomic dysfunction, manifesting as higher resting heart rates with reduced heart rate variability, has also been reported [18]. Yet despite these adverse outcomes attributed to perinatally-occurring hypoxic insults, there has been little progress towards developing clinical interventions that can be initiated during pregnancy to confer neural resiliency to at-risk newborns [19]. The absence of such interventions undermines progress towards mitigating the morbidity and mortality associated with these adverse perinatal events.
An emerging body of literature suggests that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer neural resiliency against a number of insults [20–23]. Yet, there remains a paucity of data describing whether dietary supplementation with ω-3 PUFAs can confer neuroprotection against hypoxic insults occurring in their newborns. To overcome this barrier, this study was designed to characterize the extent that maternal prenatal dietary supplementation with ω-3 PUFAs will confer neuroprotective resiliency to the newborn against hypoxia-induced dopamine dysfunction, one neurotransmitter system that is exquisitely vulnerable to such insults [24,25].