Lack of adrenomedullin affects growth and differentiation of adult neural stem/progenitor cells

Vergaño-Vera, Eva; Fernández, Ana Patricia; Hurtado-Chong, Anahí; Vicario‐Abejón, Carlos; Martı́nez, Alfredo

doi:10.1007/s00441-010-0934-3

Cited by 23 publications

(20 citation statements)

References 60 publications

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“…Previous studies (5,6) have demonstrated that the T␣-1 promoter can drive Cre expression in the CNS from an early phase (high Cre expression observed at embryonic day 11.5). Here, we have shown that this expression occurs also in the neurons of the DRG and the spinal cord.…”

Section: Discussionmentioning

confidence: 98%

“…This conditional KO of the CNS was obtained by crossing animals whose adm gene was flanked by LoxP sequences with transgenic mice expressing Cre recombinase under the T␣-1 promoter. This promoter would drive Cre expression in all cells with a neural origin from an early developmental stage, thus effectively eliminating AM expression from the CNS but allowing normal expression in other tissues (5,6). All experiments were performed with 3-to 5-month-old male littermates whose genotypes where either f/f CreϪ (named here as WT) or f/f Creϩ (conditional KOs).…”

Section: Animalsmentioning

confidence: 99%

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Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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Adrenomedullin (AM) is a regulatory peptide, coded by the adm gene, which is involved in numerous physiological processes, including pain sensitivity. Previous studies have shown that intrathecal injection of AM induced hyperalgesia in the rat. Here, we explore pain sensitivity in a mouse conditional knockout for adm in neurons of the central nervous system, including the spinal cord and dorsal root ganglia. Double immunofluorescence in wild-type (WT) animals shows that AM immunoreactivity is found in calcitonin gene-related peptide-positive neurons of the dorsal root ganglia but not in neurons that bind isolectin B4. Mice lacking adm had modified expression of canonical sensorial neuropeptides, having significantly more calcitonin gene-related peptide and less substance P and enkephalin than their WT littermates. Furthermore, the spinal cord of adm knockout mice expressed higher levels of the AM receptor components, suggesting a compensation attempt to deal with the lack of afferent AM signaling. Behavioral nociceptive tests also found differences between genotypes. In the tail-flick test, which measures mostly spinal reflexes, the adm-null animals had a longer latency than their WT counterparts. On the other hand, in the hotplate test, which requires encephalic processing, mice lacking adm had shorter latencies than normal littermates. These results suggest that AM acts as a nociceptive modulator in spinal reflexes, whereas it may have an analgesic function at higher cognitive levels. This study confirms the important role of AM in pain sensitivity processing but unveils a more complex scenario than previously surmised.

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Section: Discussionmentioning

confidence: 98%

Section: Animalsmentioning

confidence: 99%

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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“…Mice with no brain AM were less resistant to hypobaric hypoxia than wild-type mice. Using neural stem/progenitor cells prepared from the mice with no brain AM, Vergaño-Vera et al (2010) showed that the lack of AM affected growth and differentiation of adult neural stem/progenitor cells. Thus, AM2/IMD appears not to compensate for the AM defect in the brain completely, although there may be a compensatory mechanism in cell proliferation (Vergaño-Vera et al 2010).…”

Section: Difference In the (Patho)-physiological Significance Betweenmentioning

confidence: 99%

Adrenomedullin 2/Intermedin in the Hypothalamo–Pituitary–Adrenal Axis

et al. 2010

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Adrenomedullin 2/intermedin (AM2/IMD) is a new member of the calcitonin/calcitonin gene-related peptide (CGRP) family. CGRP, adrenomedullin (AM), and AM2/IMD share the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP). The CRLR/RAMP2 or CRLR/RAMP3 complex forms the AM receptor, whereas the CRLR/RAMP1 forms the CGRP receptor. AM2/IMD binds non-selectively to all three CRLR/RAMP complexes. AM2/IMD has various actions, such as a potent vasodilator action and a protective action against oxidative stress, like AM and CGRP. When administered intracerebroventricularly, AM2/IMD stimulates the sympathetic nervous system and increases blood pressure. In human hypothalamus, AM2/IMD is expressed in the paraventricular and supraoptic nuclei and colocalized with arginine vasopressin. Anterior pituitary cells were diffusely immunostained for AM2/IMD. AM2/IMD stimulates the release of ACTH, prolactin, and oxytocin, but suppresses GH release. Some of these pituitary actions of AM2/IMD have been supposed to be mediated by an unidentified unique receptor for AM2/IMD. In the adrenal gland, immunoreactive (IR)-AM2/IMD and IR-AM were detected in the medulla, while the degree of IR-AM2/IMD and IR-AM in the cortex was relatively weak or undetectable. Furthermore, AM2/IMD and AM were expressed in adrenocortical tumors, such as aldosterone-secreting adenomas, and pheochromocytomas. CRLR and RAMPs are expressed in the hypothalamus, pituitaries, adrenal glands, and adrenal tumors. Thus, AM2/IMD is expressed in every endocrine organ of the hypothalamo-pituitary-adrenal axis together with its receptor. AM2/IMD may act as a neurotransmitter or modulator in the brain and as a paracrine/autocrine regulator in the hypothalamo-pituitary-adrenal axis.

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“…The study of neuronal morphology remains important to many areas of basic neuroscience, including neuritogenesis (Da Silva and Dotti, 2002;Gupton and Gertler, 2010), development (Budd et al, 2010;Ristanovich et al, 2010), synaptogenesis and plasticity (Banker and Cowan, 1977;Krivosheya et al, 2008;Sutton and Schuman, 2006), as well as axon specification and polarity (de Anda et al, 2008;Dertinger et al, 2002;Fukata et al, 2002;Vogt et al, 2004). It is also critical for areas of applied neuroscience, including stem cell transplantation (Lanfer et al, 2010;Vergano-Vera et al, 2010) and the study of neuronal response to regeneration scaffolds that rely on novel biomaterials, the focus of our laboratory and that of many others (Chew et al, 2008;Corey et al, 2007Corey et al, , 2008Gertz et al, 2010;Kim et al, 2008;Wang et al, 2009;Johnson et al, 2010).…”

Section: Introductionmentioning

confidence: 95%