Developmental profile of messenger RNA for the corticotropin-releasing hormone receptor in the rat limbic system

Abstract

The ontogeny of corticotropin-releasing hormone (CRH) receptor messenger ribonucleic acid (mRNA) in rat brain, using in situ hybridization, is the focus of this study. The developmental profile of CRH receptor using binding assays and receptor autoradiography has been reported, but may be confounded by the presence of a binding protein. The recent cloning of the rat CRH receptor gene has permitted the use of in situ hybridization histochemistry to map the distribution of cells expressing CRH receptor mRNA in the developing brain. We used antisense 35 S-labeled oligodeoxynucleotide probes for the two reported splice-variants of the CRH receptor mRNA, which yielded essentially identical localization patterns. CRH receptor mRNA was clearly detectable in infant brain starting on the second postnatal day. Signal in hippocampal CA1, CA2 and CA3a increased to 300-600% of adult levels by postnatal day 6 with a subsequent gradual decline. In the amygdala, in contrast, CRH receptor mRNA abundance increased steadily between the second and the ninth postnatal days, to levels twice higher than those in the adult. In the cortex, CRH receptor mRNA levels were high on postnatal day 2 and decreased to adult levels by day 12. Transient signal over the hypothalamic paraventricular nucleus, observed on the second postnatal day, was not evident at older ages. These results demonstrate robust synthesis of CRH receptor as early as on the second postnatal day and unique region-specific developmental profiles for CRH receptor gene expression.

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

“…In addition, CRH receptors, particularly corticotropinreleasing factor-1, shown to mediate the excitation-promoting actions of CRH, 4 are abundantly expressed in hippocampal pyramidal cells. 2,13,15 These data support the notion that, in the hippocampus, CRH modulates synaptic neurotransmission; in turn, expression of the CRH gene is controlled by hippocampal circuit activation.…”

“…In addition, CRH receptors, particularly corticotropinreleasing factor-1, shown to mediate the excitation-promoting actions of CRH, 4 are abundantly expressed in hippocampal pyramidal cells. 2,13,15 These data support the notion that, in the hippocampus, CRH modulates synaptic neurotransmission; in turn, expression of the CRH gene is controlled by hippocampal circuit activation.The requirement for stimulation of hippocampal neurons 4,14,56 for up-regulation of hippocampal CRH expression, suggested in the current study, is further illustrated by the effects of barbiturates: hyperthermia-induced hippocampal CRH mRNA expression was abolished (in CA1) or attenuated (in CA3) by barbiturate pretreatment, providing clues for the mechanisms for CRH mRNA activation in the hippocampus: Pentobarbital interferes with polysynaptic neurotransmission by modulating GABA A receptors. Indeed, it eliminated the hyperthermia-induced intense hippocampal neuronal stimulation, as evident from behavioral and electrophysiological criteria (Fig.…”

“…24 Abundant target neurons for CRH, expressing cognate receptors, have been demonstrated in the hippocampus. 2,13,15 In addition, physiological effects of CRH on hippocampal neurons have been found, including facilitation of memory retention and increased protein phosphorylation. 10,33 Conversely, abnormalities of CRH-mediated limbic neurotransmission may contribute to neurological disorders such as depression 43 or Alzheimer's disease.…”

The developmental profile of the corticotropin releasing factor receptor (CRF2) in rat brain predicts distinct age-specific functions

“…Two major types of CRF receptors have been characterized and named CRF 1 and CRF 2 [10,23,30]. The CRF 2 receptor exists in at least two isoforms [22].…”

“…Two major types of CRF receptors have been characterized and named CRF 1 and CRF 2 [10,23,30]. The CRF 2 receptor exists in at least two isoforms [22]. The distribution and expression of the two CRF receptors have been documented in the adult rat brain [10,31,47].…”