Disease relevance of Gal

• These results demonstrate that galanin acts an endogenous neuroprotective factor to the hippocampus and imply that a galanin agonist might have therapeutic uses in some forms of brain injury [1].
• Neuropeptide Y (NPY) and galanin have both been implicated in the regulation of body weight, yet mice bearing deletions of either of these molecules have unremarkable metabolic phenotypes [2].
• Obesity and endocrine dysfunction in mice with deletions of both neuropeptide Y and galanin [2].
• Galanin is a 29-amino-acid peptide expressed in dorsal root ganglion (DRG) neurones and spinal dorsal horn neurones [3].
• Acute hypoxia (5% O(2) for 60 min) elicited increases in TH and GAL mRNA levels in the LC after 24 h [4].

Psychiatry related information on Gal

• The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease [5].
• GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task [5].
• The neuropeptide galanin and its receptors are expressed in the locus coeruleus (LC), a brain area associated with drug dependence and withdrawal [6].
• These data support the hypothesis that galanin may have a role in functions related to mood states including affective disorders [7].
• In the activity cage test, galanin overexpression counteracted the age-induced decrease in exploratory behavior [8].

High impact information on Gal

• Galanin is widely distributed in enteric nerve terminals lining the gastrointestinal tract [9].
• The hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin, CRH (ref. 3) and GLP-1 (ref. 4), have been implicated in the mediation of these effects [10].
• To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Gal alpha-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the alpha-1,2-fucosyl lactosamine moiety (H-epitope) [11].
• The mechanisms whereby hormones and neurotransmitters such as adrenaline, galanin and somatostatin, which are released by intraislet nerve endings and the pancreatic D cells, produce inhibition of insulin secretion are not clear [12].
• Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor [13].

Chemical compound and disease context of Gal

• The administration of estradiol-17beta induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph [14].
• The effects of galanin, somatostatin, and clonidine on [Ca2+]i were abolished in beta-cells treated with pertussis toxin [15].
• Receptor activation by galanin in COS-7 cells stimulated phosphoinositide metabolism, which was not reversed by pertussis toxin [16].
• Galanin contributes to the excess colonic fluid secretion observed in dextran sulfate sodium murine colitis [17].
• Neither GALP((1-21)) (the fragment containing the galanin-homologous sequence) nor GALP((22-60)) (the C-terminal portion of the GALP molecule lacking sequence identity with galanin) had any discernable effect on food intake, body weight or circulating LH [18].

Biological context of Gal

• We therefore hypothesized that galanin might also act in a similar manner in the CNS, reducing cell death in hippocampal models of excitotoxicity [1].
• Estradiol treatment for one week elevated GAL gene expression 30-40 fold in the wild-type mouse pituitary [19].
• Perinatal nicotine attenuates the hypoxia-induced up-regulation of tyrosine hydroxylase and galanin mRNA in locus ceruleus of the newborn mouse [4].
• Both c-fos immunoreactivity, a marker of neuronal activity, and phosphorylation of tyrosine hydroxylase at Ser-40, a marker of cAMP levels, are decreased in the locus coeruleus by galnon treatment after morphine withdrawal, suggesting a possible molecular mechanism for the behavioral effects of galanin [20].
• Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release [21].

Anatomical context of Gal

• Galanin acts as a neuroprotective factor to the hippocampus [1].
• We have recently demonstrated that peripheral sensory neurons depend on galanin for neurite extension after injury, mediated by activation of the second galanin receptor subtype (GALR2) [1].
• The expression of the neuropeptide galanin is markedly up-regulated in many areas of the central and peripheral nervous system after injury [1].
• Galanin mRNA was increased in the hypothalamus of NPY(-/-) mice, providing evidence of compensatory regulation in single mutants [2].
• Galanin also plays a trophic role in the adult animal, and the rate of peripheral nerve regeneration and neurite outgrowth is reduced in adult Gal-KO mice [22].

Associations of Gal with chemical compounds

• Similarly, exposure to glutamate or staurosporine induced significantly more neuronal cell death in galanin knockout organotypic and dispersed primary hippocampal cultures than in WT controls [1].
• Kainate-induced hippocampal cell death was greater in both the CA1 and CA3 regions of galanin knockout animals than in WT controls [1].
• Neurokinin A and galanin in the thyroid gland: neuronal localization [23].
• Galanin, substance P and dynorphin were also co-localized with serotonin in a few axons of the deep dorsal horn and in the gray matter around the central canal [24].
• Moreover, hypoxia-induced increases in TH and GAL mRNA levels in the LC were not observed in nicotine-treated pups [4].

Physical interactions of Gal

• In the DG, 57+/-5% of the galanin binding sites were GalR2, and the remaining population corresponded to GalR1 [25].
• Moreover, the increase in galanin binding sites seems to be caused by increased transcription or stabilization of the galanin receptor 1 (GalR1) gene, because there is a dramatic increase in mRNA levels following withdrawal in the LC [6].
• Galanin attenuates cyclic AMP regulatory element-binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures [26].

Co-localisations of Gal

• The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents [27].

Regulatory relationships of Gal

• Galanin inhibits gastric acid secretion through a somatostatin-independent mechanism in mice [28].
• Unlike in rats, the proportion of GnRH cells coexpressing galanin in mice was high following ovariectomy (OVX) and the treatment of OVX mice with estrogen decreased the number of GnRH cells with galanin-IR [29].
• The present results show that overexpression of galanin under the control of the DBH promoter does not only occur, as expected in these mice, in noradrenline/adrenaline neurons but also in DRG neurons, particularly in large and medium-sized NPs [30].
• The ER in GT1-7 cells is biologically active because 17beta-estradiol enhances both endogenous GAL gene expression and an ERE-driven reporter gene [31].
• Galanin down-regulates microglial tumor necrosis factor-alpha production by a post-transcriptional mechanism [32].

Other interactions of Gal

• Adult GalR2-MUT animals also have a one third reduction in neurite outgrowth from cultured DRG neurons that cannot be rescued by either galanin or a high-affinity GalR2/3 agonist [22].
• Estradiol induces galanin gene expression in the pituitary of the mouse in an estrogen receptor alpha-dependent manner [19].
• Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice [33].
• Somatostatin antibody injected i.v. increased acid secretion by 3.5-fold over basal levels but did not modify the antisecretory effects of galanin [28].
• Urethane-anesthetized SSTR2 knockout mice had a basal secretion 14-fold higher than wild-type animals, that was inhibited by galanin (10 and 20 microg/kg/h) by 49 and 31% respectively [28].

Analytical, diagnostic and therapeutic context of Gal

• Cervical vagotomy (extirpation of the nodose ganglion) reduced the number of NKA- and GAL-containing fibers in the thyroid by approximately 50% [23].
• Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and TH-LI and that galanin in these baskets is strongly influenced by peripheral axotomy [34].
• Galanin acts at three G-protein-coupled receptors, galanin receptors (GalR1-3), each expressed in the DRGs as suggested by in situ hybridization and/or reverse transcriptase-polymerase chain reaction [3].
• After lumbar sympathectomy both galanin- and TH-immunoreactive baskets disappeared, suggesting a sympathetic origin [34].
• RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice [21].

References