Region-Specific Onset of Handling-Induced Changes in Corticotropin-Releasing Factor and Glucocorticoid Receptor Expression

Fenoglio, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Chen, Yuncai; Baram, Tallie Z.

doi:10.1210/en.2004-0111

Cited by 60 publications

(45 citation statements)

References 31 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As we show here with respect to CRF and as we and others have previously reported, both routine animal husbandry protocols (eg AFR) and the HMS15 protocol produce similar neurobehavioral outcomes Pryce et al, 2001;Pryce and Feldon, 2003). However, Fenoglio et al (2004) recently reported that handling during PND2-9 was associated with a transient increase of CRF mRNA in the CeA by PND6, a transient increase of peptide levels in BNST, and a longlasting decrease of CRF levels in PVN beginning by PND9. Importantly, these changes in CRF preceded changes in hippocampal GR expression by many weeks.…”

Section: Discussionsupporting

confidence: 75%

“…Thus, it appears that central CRF systems represent a major target of neonatal rearing conditions in the rat. In fact, this may represent a general response to a wide range of early life stressors in rodents (Dent et al, 2000;Ladd et al, 2000;Schmidt et al, 2002;Fenoglio et al, 2004), monkeys (Coplan et al, 1996), and humans (Raadsheer et al, 1994(Raadsheer et al, , 1995Austin et al, 2003;Newport et al, 2003;Carpenter et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Consequences of Neonatal Rearing on Central Corticotropin-Releasing Factor Systems in Adult Male Rat Offspring

Plotsky

Thrivikraman

Nemeroff

et al. 2005

Neuropsychopharmacol

443

321

View full text Add to dashboard Cite

In a series of studies on the long-term consequences of neonatal rearing, we compared hypothalamic and extrahypothalamic central corticotropin-releasing factor (CRF) systems in male rats reared under conditions of animal facility rearing, nonhandling (HMS0), handling with brief maternal separation for 15 min (HMS15), or handling with moderate maternal separation for 180 min (HMS180) daily from postnatal days 2-14. CRF-like immunoreactivity (CRFir) was elevated in lumbar cerebrospinal fluid of adult HMS180 and HMS0 rats relative to the other groups. In the paraventricular nucleus, central nucleus of the amygdala, bed nucleus of the stria terminalis, and locus coeruleus, CRFir and CRF mRNA levels were significantly elevated in HMS0 and HMS180 rats. Neonatal maternal separation was associated with regionally specific alterations in CRF receptor type 1 (CRF1) mRNA density in HMS180 rats. No rearing-associated differences in CRF2a binding were apparent in either the lateral septum or the ventromedial hypothalamus. These findings indicate that early rearing conditions can permanently alter the developmental set-point of central CRF systems, and potentially influence the expression of behavioral and endocrine responses to stress throughout life, thereby providing a possible neurobiological substrate for the relationship between early life events and increased vulnerability for hypothalamic-pituitary-adrenal axis and coping skill alterations and the frequency of mood disorders in patients with a history of such experiences.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Long-Term Consequences of Neonatal Rearing on Central Corticotropin-Releasing Factor Systems in Adult Male Rat Offspring

Plotsky

Thrivikraman

Nemeroff

et al. 2005

Neuropsychopharmacol

443

321

View full text Add to dashboard Cite

show abstract

“…However, given that hypothalamic and brainstem NPY neurons act as integrators between stress signals and the neuroendocrine response to stress (34,35) and that NPY stimulates HPA axis via CRH neurons (25), the increase of NPY immunoreactive fibers in PVNmp may also contribute to the enhancement of hypothalamic CRH immunoreactivity and higher serum corticosterone observed in Npy1r rfb mice.…”

Section: Discussionmentioning

confidence: 99%

Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care

Bertocchi

Oberto

Longo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1r rfb ). Npy1r rfb mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1r rfb mutants also had a hyperactive hypothalamic-pituitaryadrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1r rfb and Npy1r 2lox mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis. where it is involved in the regulation of anxiety, stress reactions, energy balance, circadian rhythms, and cognition (1-3). Clinical studies suggest that NPY plays an important role in the response to stress and in psychiatric disorders (4). In humans, NPY haploinsufficiency is correlated with characteristic brain responses to emotional and stress challenges and with trait anxiety (5). Intracerebroventricular injection of NPY reduces both anxiety-and stress-related behavior in several animal models, an effect that is primarily mediated by Y1 receptors (Y1Rs) expressed in amygdala, hippocampus, and locus coeruleus (6-9). The implications of a role of endogenous NPY in acting via Y1R to control emotionality, mood, and stress reactions have been probed with Y1R-selective antagonists and antisense oligonucleotides (1). NPY exerts its anxiolytic-like effect in the brain via interactions with the hypothalamic-pituitaryadrenocortical (HPA) axis and corticosteroids. Indeed, a functional antagonism between NPY and corticotropin releasing hormone (CRH) has been demonstrated in various CNS nuclei along the stress/anxiety circuits (10).In addition to its crucial role in emotional behavior, NPY potently stimulates feeding, reduces energy expenditure, and induces obesity via the activation of Y1R expressed in the hypothalamus (1). However, global Npy1r gene knockout mice showed only minor deficiencies in energy homeostasis, feeding, and anxiety (11)(12)(13)(14).To study the function of Y1R expressed in the limbic system and to exclude effects induced by the Npy1r gene inactivation in early development, we restricted the ablation of Y1R to excitatory neurons in the postnatal forebrain of mice by using the Cre-loxP system (Fig. 1A). In addition, because early postnatal environment can modulate NPY levels (15), gene-targeted pups were reared by two diffe...

show abstract

“…For example, short daily periods (15 min) of separation from the mother have been used to model mild stress and may have positive effects on hippocampal function. These positive effects are likely mediated by the nurturing input from the mother upon return of the pups to the cage [89,8,48,49]. In contrast, repeated prolonged (3 h) separation from the mother [113] or a single 24 h separation [46] have been considered models of more severe acute/subacute stress.…”

Section: Animal Models Of 'Psychological' Stress Early In Life That Amentioning

confidence: 99%

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

Fenoglio¹,

Brunson²,

Baram³

2006

Frontiers in Neuroendocrinology

186

138

View full text Add to dashboard Cite

Whereas genetic factors contribute crucially to brain function, early-life events, including stress, exert long-lasting influence on neuronal function. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning and memory. Using a novel immaturerodent model, we describe the deleterious consequences of chronic early-life 'psychological' stress on hippocampus-dependent cognitive tasks. We review the cellular mechanisms involved and discuss the roles of stress-mediating molecules, including corticotropin releasing hormone, in the process by which stress impacts the structure and function of hippocampal neurons. KeywordsNeonatal; Rat; Human; Stress; Memory; Hippocampus; Corticotropin releasing hormone; CRF; Hypothalamic pituitary adrenal axis; Neuroplasticity Early-life events interact with genetic factors to influence hippocampal function long-termBrain function and dysfunction throughout life are determined by the interaction of genetic factors with 'acquired' environmental events, signals and stimuli [100]. Events that occur early in life are capable of exerting effects that persist throughout adulthood. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning, memory storage and retrieval, and general cognitive function [105,41,65]. Indeed, early-life events, via complex interactions with genetic factors [106,120], have been suspected to be a major determinant of smaller hippocampal volume and long-term cognitive dysfunction in preterm infants [111,17] and may play a role in certain affective and dementing disorders in the adult and aging human [100,26,120]. This review focuses on the mechanisms by which certain early-life events influence populations of hippocampal neurons acutely, and impact the function and integrity of the hippocampus long-term. Studying early-life stress may be used to probe the molecular mechanisms involved in experience-evoked hippocampal neuroplasticityStress may provide a salient example of early-life experience that might exert long-lasting influence on the brain, because (1) over 50% of the world's children are exposed to stress [139] and (2) evidence from both human and animal studies suggests that early-life stress has profound effects on cognitive function and emotional health.Stress has been shown to influence the hippocampus in a number of important ways. Whereas acute mild stress rapidly enhances synaptic efficacy and learning and memory processes [131,45,91,123], chronic or severe activation of the stress response early in life has been shown to be potentially injurious in both humans [6,120,147] and experimental animals [120,31]. For example, severe childhood psychological stress (neglect and abuse) correlates with a higher incidence of learning disabilities later in life, including those learning and memory functions requiring an intact hippocampus [121,50]. Further, MRI studies have suggested that adults subjected to abuse (a measure of chronic stress) ...

show abstract

Region-Specific Onset of Handling-Induced Changes in Corticotropin-Releasing Factor and Glucocorticoid Receptor Expression

Cited by 60 publications

References 31 publications

Long-Term Consequences of Neonatal Rearing on Central Corticotropin-Releasing Factor Systems in Adult Male Rat Offspring

Long-Term Consequences of Neonatal Rearing on Central Corticotropin-Releasing Factor Systems in Adult Male Rat Offspring

Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

Contact Info

Product

Resources

About