Differential Regulation of the Expression of Corticotropin-Releasing Factor Receptor Type 2 (CRF₂) in Hypothalamus and Amygdala of the Immature Rat by Sensory Input and Food Intake

Abstract

The physiological consequences of activating corticotropin-releasing factor receptor type 2 (CRF2) are not fully understood. The neuroanatomic distribution of this CRF receptor family member is consistent with roles in mediating the actions of CRF and similar ligands on food intake control and integrative aspects of stress-related behaviors. However, CRF2 expression in the adult rat is not influenced by stress, corticosterone (CORT), or food intake. In immature rat we have demonstrated striking downregulation of CRF2mRNA in hypothalamic ventromedial nucleus (VMH) after 24 hr of maternal deprivation, a paradigm consisting of both physiological/psychological stress and food deprivation. The current study aimed to distinguish which element or elements of maternal deprivation govern CRF2mRNA expression by isolating the effects of food intake and discrete maternal sensory cues on CRF2mRNA levels in VMH and in reciprocally communicating amygdala nuclei. In maternally deprived pups, CRF2mRNA levels in VMH and basomedial (BMA) and medial (MEA) amygdala nuclei were 62, 72, and 102% of control levels, respectively. Sensory inputs of grooming and handling as well as of the pups' own suckling activity-but not food intake-fully restored CRF2mRNA expression in VMH. In contrast, all manipulations tended to increase CRF2mRNA levels in BMA of maternally deprived rats, and surrogate grooming increased CRF2mRNA expression significantly above that of nondeprived controls. CRF2mRNA expression was not influenced significantly by plasma adrenocorticotropic hormone (ACTH) and CORT levels. Thus, in the immature rat, (1) CRF2 expression is regulated differentially in hypothalamic and amygdala regions, and (2) CRF2mRNA levels in VMH are governed primarily by maternal or suckling-derived sensory input rather than food intake or peripheral stress hormones. These findings indicate a region-specific regulation of CRF2mRNA, supporting the participation of the receptor in neurochemically defined circuits integrating sensory cues to influence specific behavioral and visceral functions.

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

“…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.…”

“…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.However, absence of the mother influences critical physiological parameters such as nutrition (and thus cannot be used chronically), and eliminates maternal contact and grooming [46]. Importantly, maternal separation fails to reproduce the chronic early-life psychological stress that is found in humans and typically results from abnormal interactions with a present mother.…”

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat

“…19,20 In brief, 20-μm coronal sections were collected on gelatin-coated slides and stored at −80°C. Sections were thawed, air-dried, fixed in paraformaldehyde, dehydrated and rehydrated through graded ethanols, exposed to 0.25% acetic anhydride in 0.1 M triethanolamine (pH 8) and dehydrated.…”

“…16 After hybridization, sections were digested with 200 μg/ml RNase A (Calbiochem, La Jolla, CA) for 30 min at 37°C. Sections underwent serial washes of increasing stringency at 55°C, the most stringent at 0.03 × standard saline citrate for 1 h. 19,20 Hybridized sections were apposed to film (Hyperfilm βMax, Amersham, IL) for seven to 14 days. Selected sections were also dipped in emulsion (NTB-2, Eastman Kodak, Rochester, NY) and exposed for four to six weeks.…”

“…19,23 Digitized images of each brain section were acquired using a StudioStar scanner (AGFA, resolution 1200 × 1200 dots per inch) and analysed using the ImageTool software program (University of Texas Health Science Center, San Antonio, TX, version 1.25). Densities were calibrated using 14 C standards and are expressed in μCi/g after correcting for background by subtracting the density of the hybridization signal over the corpus callosum.…”