Eghbal-Ahmadi M, Avishai-Eliner S, Hatalski C G, Baram T Z
Departments of Anatomy and Neurobiology and Pediatrics, University of California at Irvine, Irvine, California 92697-4475, USA.
J Neurosci. 1999 May 15;19(10):3982-91. doi: 10.1523/JNEUROSCI.19-10-03982.1999.
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.
激活2型促肾上腺皮质激素释放因子受体(CRF2)的生理后果尚未完全明确。该CRF受体家族成员的神经解剖分布与介导CRF及类似配体在食物摄入控制和应激相关行为的整合方面的作用一致。然而,成年大鼠中CRF2的表达不受应激、皮质酮(CORT)或食物摄入的影响。在未成熟大鼠中,我们已证明母婴分离24小时后,下丘脑腹内侧核(VMH)中CRF2mRNA显著下调,母婴分离是一种包含生理/心理应激和食物剥夺的模式。当前研究旨在通过分离食物摄入和离散的母体感觉线索对VMH以及相互连通的杏仁核核团中CRF2mRNA水平的影响,来区分母婴分离的哪些因素决定CRF2mRNA的表达。在母婴分离的幼崽中,VMH、基底内侧(BMA)和内侧(MEA)杏仁核核团中的CRF2mRNA水平分别为对照水平的62%、72%和102%。梳理和处理以及幼崽自身的吸吮活动的感觉输入——而非食物摄入——可完全恢复VMH中CRF2mRNA的表达。相比之下,所有操作都倾向于增加母婴分离大鼠BMA中的CRF2mRNA水平,替代梳理使CRF2mRNA表达显著高于未分离对照。CRF2mRNA的表达不受血浆促肾上腺皮质激素(ACTH)和CORT水平的显著影响。因此,在未成熟大鼠中,(1)CRF2在丘脑和杏仁核区域的表达受到不同调节,并且(2)VMH中的CRF2mRNA水平主要由母体或哺乳衍生的感觉输入决定,而非食物摄入或外周应激激素。这些发现表明CRF2mRNA存在区域特异性调节,支持该受体参与将感觉线索整合以影响特定行为和内脏功能的神经化学定义回路。