6875 Boulevard Lasalle
Dept of Psychiatry and Dept of Anatomy & Cell Biology
Director of Technology - Douglas Hospital Research Centre
Early stress, maternal regulation and neuroendocrine development
Optimal early development in most species is critically dependent upon a stable relationship between the mother and her infant. The research focus of our laboratory concentrates on the reciprocal nature of this dyad, with respect to the regulation of stress responsiveness in both mother and offspring and the long term neurophysiological and behavioral consequences of early environmental stressors in the offspring. Non-genomic maternal influences on the infant are primarily routed through changes in nutrition and maternal care in the early postnatal period. It is now well recognized in rodents and to a certain extent in humans that variations in maternal care for instance, are associated with molecular changes in the central nervous system leading to modifications in stress responsiveness and coping mechanisms in the long-term. Dietary influences are critical not only to regulate infant growth, but also to modulate the response of the neuroendocrine system to stress and possibly to influence some aspects of brain development. In particular, we examine the consequences of early exposure to high fat diet on the development of reward pathways and preference towards specific food intake in the offspring and investigate the role of metabolic hormones such as leptin, ghrelin and insulin in mediating these effects. Dietary fat intake is also important in providing precursor molecules that have important neurotransmitter functions such as endocannabinoids, which are lipid-derived retrograde transmitters and actively participate in regulation of stress responses in the adult. We are actively seeking to define their role in the establishment of vulnerability to stress during the developmental period.
While maternal regulatory influences are critical for the development of the stress axis (HPA axis) and behavioral regulation in the offspring, there is also evidence to support the reverse regulatory influence in which maternal state is profoundly affected by stimulation from the young. Indeed, earlier studies have shown that infant temperament might influence mothering style and that sensory stimuli provided by the infant are able to modify physiological and behavioral responses in the mother. During the period of lactation, mothers exhibit lower neuroendocrine and behavioral responses to several types of stressors except possibly those representing a threat to the infant. This ability to “filter” relevant from irrelevant stimuli while caring for their young might be viewed as adaptive for the mother-infant dyad and emphasizes the importance of the concept of stimulus salience in regulating neuroendocrine and behavioral responses in the mother. Such a concept might apply to post-partum mothers as well since they exhibit a certain degree of stress hyporesponsiveness, in particular breast-feeding mothers. Studies directed towards understanding the mechanisms by which infants can regulate their mothers’ stress responses are currently underway in the laboratory as we are seeking to identify neuronal structures that are part of a “salience filter network” in the maternal brain. These studies should help us identify whether the inability to adequately “filter” stressful stimuli could at least in part be associated with the development of postpartum depression and whether breastfeeding in high risk populations could be seen as a protective factor against exaggerated responses to challenges in both mother and offspring.
Wood C, Walker CD 2015 Fetal and Neonatal HPA Axis. Comprehensive Physiology, (in press)
Walker C-D, Woodside B. 2015 “Mothering influences on offspring stress response mechanisms”. In: INF Masterclass in Neuroendocrinology Series: “Neuroendocrinology of Stress”. ed J A Russell & M J Shipston: Wiley-Blackwell. Chap 13, p279
Naef L, Gjerde E, Long H, Richard D, Walker CD 2014 Neonatal onset of leptin signaling in dopamine neurons of the ventral tegmental area in the rat. J Neuroendocrinol. 2014 Dec;26(12):835-43
Campbell-Yeo M, Johnston C, Benoit B, Latimer M, Vincer M, Walker CD, Streiner D, Inglis D, Caddell K. 2013 Trial of repeated analgesia with Kangaroo Mother Care (TRAKC Trial). BMC Pediatr. 2013 Nov 9;13:182
Naef L, Gratton A, Walker CD.2013 Exposure to high fat during early development impairs adaptations in dopamine and neuroendocrine responses to repeated stress.Stress. 2013 Sep;16(5):540-8. doi: 10.3109/10253890.2013.805321.
Buwembo A, Long H, Walker CD 2013 Participation of endocannabinoids in rapid suppression of stress responses by glucocorticoids in neonates.Neuroscience. 2013 Sep 26;249:154-61.
Naef L, Moquin L, Gratton A, Walker CD 2013 Blunted anticipatory dopamine responses to food in animals exposed to high-fat during early development. Int J Obes (Lond). 2013 Jun;37(6):885-8.
Walker C-D. 2010 Maternal touch and feed as critical regulators of behavioural and stress responses in the offspring. Dev Psychobiol. Nov;52(7):638-50.2010 Sep 22.
DeMedeiros C, Fleming AS, Johnston CC, Walker C-D. 2009 Artificial rearing of rat pups reveals the beneficial effects of mother care on neonatal inflammation and adult sensitivity to pain. Pediatric Res. 66(3):272-7
Léonhardt MM, Matthews SG, Meaney MJ, Walker C-D 2007 Psychological stress as a model of early maternal adversity: diurnal modulation of corticosterone responses and changes in maternal behaviour. Horm Behav. 2007 Jan;51(1):77-88
Dr Claire-Dominique Walker obtained her PhD from the University of Geneva, Switzerland and trained both at the Salk Institute and at the University of California San Francisco before joining McGill University and the Douglas Institute in Mental Health. She is currently Professor in the Dept of Psychiatry and Anatomy & Cell Biology at McGill University. The focus of her research is to understand the long term consequences of early stress and environmental challenges on the development of the brain and adult vulnerability to pathologies. Her current work examines how the neuronal pathways that regulate stress responses and reward systems in the offspring are modified by maternal nutrition and endocannabinoids, leading to increased susceptibility to mood disorders and metabolic diseases. To parallel the condition of human pre-term infants subjected to early pain, Dr Walker has also developed an animal model of neonatal exposure to repeated pain to investigate long term effects on pain sensitivity, behavior and brain morphology. Her research interests have expanded to examine the role of infants on maternal stress responsiveness in order to better understand the reciprocal nature of the mother-infant dyad.
1994-1997: NSERC Women’s Faculty Award
1994-1995: FRSQ Chercheur Boursier Junior I (Fondation des maladies mentales)
1997-1999: NSERC Women’s Faculty Award
1997-2000: FRSQ Chercheur Boursier Junior II
2000-2004: FRSQ Chercheur Boursier Senior
2002: CCNP Young Investigator Award
Angela Guadagno, MSc student
Emily Opala, MSc student
Hong Long, Research assistant
Silvanna Verlezza, research assistant
Past members (last 5 years):
Xiu Jing Cao (PhD, University of Science and Technology of China)
Katharina Hillerer (PhD, University of Regensburg, Germany)
Ryan McLaughlin (PhD, UBC, Canada)
Lindsay Naef, PhD
Francis Bambico, PhD
Cynthia de Medeiros, MSc
Alice Buwembo, MSc
Eva Gjerde, MSc
MinGi Cho, MSc
The Impact of Neonatal Simulations on Trainees' Stress and Performance: A Parallel-Group Randomized Trial. Pediatr Crit Care Med. 2017;18(5):434-441.
Fetal and Neonatal HPA Axis. Compr Physiol. 2015;6(1):33-62.
Neonatal onset of leptin signalling in dopamine neurones of the ventral tegmental area in the rat. J Neuroendocrinol. 2014;26(12):835-43.
Co-bedding between preterm twins attenuates stress response after heel lance: results of a randomized trial. Clin J Pain. 2014;30(7):598-604.
Trial of repeated analgesia with Kangaroo Mother Care (TRAKC Trial). BMC Pediatr. 2013;13:182.
Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial. Clin J Pain. 2013;29(9):824-9.