| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PERSPECTIVES |
Department of Physiology and Institute for Neuroscience, North-western University, Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL 60611-3008, USA Email: dm{at}north-western.edu
The epigenetic effect of deprivation and stress on brain development is one of the most enduring topics in neurobiology and one that arguably has had the most far reaching influences on modern societies. Persistent deficits in perception, cognition, and social development are attributed to maternal separation and/or environmental deprivation of human infants. Given the retrospective nature of these human studies, the animal experiments they have inspired are particularly significant insofar as objective changes in physiology, neuronal structure and brain size follow manipulations of the perinatal sensory environment.
In a striking demonstration of the long-term impact of neonatal stress on the physiological status of the adult rat, in this issue of The Journal of Physiology Genest et al. (2004) describe persisting changes in the organization of respiration (and blood pressure) consequent to prolonged neonatal maternal separation stress. Significantly, alterations in blood pressure and respiration interact with the sex of the animal. For example, blood pressure increased in neonatally stressed males but not in stressed females; males further demonstrated a greater increase in the ventilatory response to hypoxia (relative to controls) than was the case for females. In contrast, baseline minute ventilation and baseline tidal volume were higher in neonatally stressed adult females (relative to control females) but this was not the case for males.
Breathing may be particularly sensitive to changes in emotional state. Fear evokes the fight-or-flight response for which an increase in breathing complements an anticipated increase in motor activity. The behavioural effects of neonatal maternal separation are complex and depend on both the timing and the duration of the separation (Lehmann et al. 1999). When separation is applied, as in the experiments of Genest et al. (2004), it also produces persisting changes in adult anxiety levels which, as with the altered ventilatory responses, include sex differences (Wigger & Neumann, 1999). Anxiety, in turn, is generally accompanied by an increase in minute ventilation (Ley, 1999). It should be mentioned, however, that in the experiments of Wigger & Neumann (1999), anxiety levels were generally greater in neonatally stressed adult male rats, while in the report by Genest et al. (2004) baseline minute ventilation is greater in neonatally stressed females.
The linkage between hyperventilation and anxiety disorders leads to a question as to whether the respiratory changes are a consequence of increased anxiety levels, or whether an independently evoked abnormal breathing pattern (hyperventilation) elicits anxiety (Ley, 1999). Disordered breathing has been proposed as aetiological in panic disorder, an extreme form of anxiety. Two different mechanisms have been proposed to explain this linkage (Wilhelm et al. 2001). In one, a ‘suffocation false alarm’ is hypothesized in which the respiratory control system has an abnormally high carbon dioxide sensitivity that can trigger sensations of air hunger and panic. Alternatively, a cognitive-behavioural theory of panic is based on the concept of an interoceptive feedback loop between anxiety and hyperventilation in which mild anxiety elicits cardiovascular sensations (palpitations) and respiratory sensations. Hypochondriacal interpretation of these sensations could then lead to more anxiety and more hyperventilation that further augment the intensity of the cardiorespiratory feedback. This would therefore result in a vicious cycle of increasingly negative sensations and enhanced anxiety (Wilhelm et al. 2001). The possibility that disordered breathing, whatever its origin, contributes to increased anxiety/panic has suggested the possibility that behavioural modification of breathing patterns could possibly be prophylactic, or help to quell ongoing anxiety; alternatively, controlled breathing patterns might be effective in altering mood in general. So far, definitive evidence for this postulate is lacking, but as reviewed by Ley (1999) several studies offer tentative support. If further research reinforces the proposed two-way interaction between mood and respiration, it would add credibility to some of the extant traditional behavioural approaches to personal development that often incorporate controlled breathing techniques.
In the context of breathing and anxiety it is notable that the most effective pharmacological agents for treating panic disorders are serotonin reuptake inhibitors. It has also recently been argued that both pontine (forebrain projecting), and medullary (brainstem and spinal cord projecting) serotonin neuronal populations function as CO2 chemosensors (Severson et al. 2003). Serotonin is also an essential component in long-term facilitation (LTF), an increase in the ventilatory response that occurs in adult animals and humans after repeated hypoxic challenges. This behaviour also demonstrates sex-specific changes during ageing, with females demonstrating increased LTF with ageing, while the LTF for males declines (Behan et al. 2002).
Interactions between emotional responses and respiration are potentially served by interconnecting pathways relating forebrain circuits, thought to be involved in the generation of emotional responses, and the brainstem circuits responsible for generating breathing. Forebrain structures include the paraventricular hypothalamic nucleus, which integrates a variety of forebrain inputs relative to the stress response and mediates pituitary corticotrophin release (Herman et al. 2003) while contributing afferents to the brainstem and spinal cord. Other likely participating structures include the nucleus of the solitary tract and the pontine parabrachial complex, since these relay afferent information relative to homeostasis and nociception to the forebrain and ventral medulla. They also receive direct descending projections from the basal forebrain including areas that activate the paraventricular nucleus in stressful situations.
Thus, the observations by Genest et al. (2004) of adult sex-specific changes in breathing consequent to neonatal stress, provide a novel avenue for developmental research via the relatively well researched brainstem structures serving the physiology of respiration. The psychophysiology of breathing and its development, however, are not well understood and touch on broad areas, fundamental to both basic and clinical neuroscience.
References
Behan M, Zabka AG & Mitchell GS (2002). Respir Physiol Neurobiol 131, 65–77.[CrossRef][Medline]
Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC & Cullinan WE (2003). Front Neuroendocrinol 24, 151–180.[CrossRef][Medline]
Genest SE, Gulemetova R, Laforest S, Drolet G & Kinkead R (2004). J Physiol 554, 543–559.
Lehmann J, Pryce CR, Bettschen D & Feldon J (1999). Pharmacol Biochem Behav 64, 705–715.[CrossRef][Medline]
Ley R (1999). Behav Mod 23, 441–479.[CrossRef]
Severson CA, Wang W, Pieribone VA, Dohle CI & Richerson GB (2003). Neurosci 6, 1139–1140.[CrossRef][Medline]
Wigger A & Neumann ID (1999). Physiol Behav 66, 293–302.[CrossRef][Medline]
Wilhelm FH, Gevirtz R & Roth WT (2001). Behav Mod 25, 513–545.[CrossRef]
This article has been cited by other articles:
|
|
 |
|
  S.-E. Genest, N. Balon, S. Laforest, G. Drolet, and R. Kinkead Neonatal maternal separation and enhancement of the hypoxic ventilatory response in rat: the role of GABAergic modulation within the paraventricular nucleus of the hypothalamus J. Physiol., August 15, 2007; 583(1): 299 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kinkead, R. Gulemetova, and A. Bairam Neonatal maternal separation enhances phrenic responses to hypoxia and carotid sinus nerve stimulation in the adult anesthetized rat J Appl Physiol, July 1, 2005; 99(1): 189 - 196. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
