Organization of Ovine Corticotropin-Releasing Factor Immunoreactive Cells and Fibers in the Rat Brain: An Immunohistochemical Study

Abstract

The distribution of corticotropin-releasing factor (CRF)-immunoreactive cells and fibers has been examined in the brains of normal adult rats, and in the brains of animals that had been pretreated with intraventricular injections of colchicine, or had been adrenalectomized 3-60 days before perfusion. The results suggest that CRF immunoreactivity is localized in at least three functionally distinct systems. First, most of the CRF-stained fibers in the neurohemal zone of the median eminence, which presumably modulate the release of ACTH and β-endorphin from the pituitary, appear to arise in the paraventricular nucleus of the hypothalamus (PVH). About 2,000 CRF-stained cells are distributed throughout all eight parts of the PVH, although a majority (80%) of the cells are concentrated in the parvocellular division, and a smaller number (about 15%) are found in parts of the magnocellular division in which oxytocinergic cells predominate. This appears to be the only CRF-stained pathway in the brain that is affected (increased staining intensity) by adrenalectomy. Second, a series of cell groups in the basal telencephalon, hypothalamus, and brain stem that are known to play a role in the mediation of autonomic responses contain CRF-stained neurons. These areas, which are interconnected by stained fibers in the medial forebrain bundle and the periventricular system, include the central nucleus of the amygdala, substantia innominata, bed nucleus of the stria terminalis, medial and lateral preoptic areas, lateral hypothalamic area, central gray, laterodorsal tegmental nucleus, locus ceruleus, parabrachial nucleus, dorsal vagal complex, and regions containing the Al and A5 catecholamine cell groups. And third, scattered CRF-stained cells are found throughout most areas of the cerebral cortex. Most such cells are confined to layers II and III in the neocortex, and their bipolar shape suggests that they are interneurons. These cells are most common in limbic regions including prefrontal areas, the cingulate gyrus, and areas bordering the rhinal fissure. Scattered immunoreactive cells are also found in dorsal parts of the dentate gyrus and Ammon’s horn. These results suggest that the PVH plays a critical role in the modulation of ACTH and β-endorphin release from the pituitary, and that CRF-containing pathways in the brain are involved in the mediation of autonomic responses.

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…CRF stellt, wie in Abschn. "Amygdala und CRF bei Sucht" dargelegt, ein anxiogenes Peptid dar, das in der zentralen Amygdala durch Angstreaktionen seine Wirkung entfaltet [2,8,9,16,27,36,39]. Die Wirkung von Oxytocin umschließt folglich die Senkung der CRF-induzierten Effekte zum einen im PVN, zum anderen in der zentralen Amygdala.…”

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

“…Therefore, central stress pathways, efficiently linking the brain and periphery, have evolved to form the hypothalamus–pituitary–adrenal axis (HPA) (Selye & Fortier, 1949; Bale & Vale, 2004; McEwen, 2008). By principle, corticotropin‐releasing hormone (CRH)‐containing( + ) neurons of the paraventricular hypothalamic nucleus (PVN) gate output from the central nervous system (Swanson & Sawchenko, 1980) with CRH (Swanson et al , 1983, 1986), through pituitary amplification steps, triggering corticosteroid release from the adrenal glands for immediate metabolic mobilization (Rivier & Vale, 1983; Kovacs & Sawchenko, 1996). Nevertheless, stress, whether due to, e.g., predation or competition for reproduction, is unlikely a singular event.…”

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

“…10,33 The source of endogenous CRH that may act on hippocampal CRH receptors has been a focus of investigation. Scattered CRH-immunoreactive neurons had been described in the hippocampal formation, 41,48,53 and recent double-labeling and ultrastructural studies have demonstrated a robust population of CRH-expressing GABAergic interneurons in the hippocampal formation of non-stressed developing rats. 59 A subpopulation of these neurons, co-expressing parvalbumin, has been identified as basket and chandelier cells.…”

“…40,54 Consistent with the functional role of hypothalamic and amygdala CRH in modulating stress responses, up-regulation of CRH expression in these two regions by challenges that activate the neuroendocrine stress response has been documented. 23,29 Teleologically, this mechanism for regulation of CRH levels should be advantageous, resulting in larger releasable pools of CRH upon subsequent challenges.In the hippocampus, the presence of CRH-expressing inter-neurons has been documented in both the mature and developing rat, 41,48,53,59 but the physiological functions of the peptide and the regulation of CRH levels at hippocampal synapses have not been fully established. Specifically, whether hippocampal CRH participates in the neuroendocrine stress response has been questioned.…”

“…21,22,24,43 CRH-producing neurons are widely but specifically distributed in the brain, 49 including a substantial CRH-expressing neuronal population located in the central nucleus of the amygdala (ACe), 22,53 a region considered as a major source for extra-endocrine CRH-mediated neurotransmission. 24 Abundant target neurons for CRH, expressing cognate receptors, have been demonstrated in the hippocampus.…”