Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considerable recent evidence suggests that in addition to its neuromodulatory role, galanin, like several other neuropeptides, also plays an important trophic role during development and after adult neural injury. Studies in our laboratory have identified high levels of galanin and galanin receptor expression in the subventricular zone, rostral migratory stream, subgranular zone of dentate gyrus and the medial corpus callosum--which include the main sites for continuing cell proliferation in both adult and developing rat brain. Galanin expression was also strongly and transiently induced in oligodendrocyte progenitor cells (OPCs) throughout the neocortex and corpus callosum by a benign physiological stimulus, cortical spreading depression (CSD). SD-like depolarization also occurs in peri-infarction areas following cerebral ischemia and is associated with proliferation of OPCs and transiently increased galanin expression. Together, these data suggest a putative role for galanin in regulating progenitor or 'stem cell' proliferation, migration and/or differentiation. Cultured adult and embryonic stem cells or 'neurospheres' express galanin and galanin receptor mRNA and preliminary studies suggest that sub-acute galanin treatment of cultured neurospheres decreases cell proliferation/survival, possibly by effects on the rate of apoptosis via GalR2 receptors.
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PMID:Galanin in neuro(glio)genesis: expression of galanin and receptors by progenitor cells in vivo and in vitro and effects of galanin on neurosphere proliferation. 1594 12

This paper reviews progress made in testing the idea that depression-related behavioral changes can arise from hyperactivity of locus coeruleus (LC) neurons which consequently inhibits activity of mesocorticolimbic dopamine neurons in the ventral tegmentum (VTA) via release of galanin from terminals on LC axons in VTA. Results from pre-clinical testing are described, including the most recent findings indicating that, in an animal model that shows long-lasting symptoms of depression, recovery to normal activity in the home cage is accelerated by infusion of a galanin receptor antagonist, galantide (M15), into VTA. Data are also described suggesting that all effective antidepressant treatments decrease activity of LC neurons.
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PMID:Testing the hypothesis that locus coeruleus hyperactivity produces depression-related changes via galanin. 1594 23

Galanin (GAL) is a potential target for novel antidepressant or anti-anxiety drug development. However, no integrated role for a "brain galanin system" in anxiety has yet emerged. It is possible that such a function may be revealed by examining the interaction of GAL with norepinephrine (NE), with which it is prominently co-localized. We showed previously that enhancing stress-activation of the NE system by yohimbine (YOH) pretreatment induced the release of GAL in central amygdala (CeA) to exert an anxiolytic effect on the elevated plus-maze. However, it remained to be demonstrated conclusively that GAL was co-released from NE terminals in CeA in this context, or if a multi-synaptic circuit activated GAL release from another afferent to CeA, or from local GAL neurons in the vicinity of CeA. In studies presented at the Third International Symposium on Galanin and Its Receptors, we utilized a combination of behavioral pharmacological approaches, testing the effects of YOH on the behavioral response to stress on the plus-maze after lesioning NE afferents to CeA with 6-OHDA, and anatomical approaches to identify GAL afferents to CeA that are activated in the context of stress with yohimbine pretreatment, to address these alternatives. Our results suggest that GAL was not co-released from noradrenergic terminals innervating CeA to exert an anxiolytic influence when noradrenergic activation was amplified by yohimbine pretreatment. Rather, it most likely originated from GAL neurons immediately adjacent to CeA that were activated by a non-noradrenergic afferent arising from elsewhere in the brain, itself activated by increasing NE activity. Thus, any role for brain GAL in anxiety remains region-specific, pathway specific, response specific and context-specific, which is likely to continue to present challenges to the development of novel agents targeting brain GAL for treatment of depression or anxiety.
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PMID:One for all or one for one: does co-transmission unify the concept of a brain galanin "system" or clarify any consistent role in anxiety? 1594 24

The behavioural phenotype of transgenic mice (3-5-months old) overexpressing galanin (GalOE mice) under the platelet-derived growth factor B (PDGF-B) promoter was evaluated in a battery of tests, including locomotor cages, light-dark exploration test, elevated plus-maze and the Porsolt forced swim test. Learning and memory were assessed in the Morris water maze task. GalOE mice showed a slight increase in spontaneous locomotor activity assessed in the locomotor cages, but the amphetamine-induced increase in locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in light-dark exploration and elevated plus-maze tests did not differ between genotypes. In the Porsolt forced swim test, GalOE mice displayed an increased time of immobility, indicative of increased learned helplessness possibly reflecting increased stress-susceptibility and/or depression-like behaviour. GalOE mice showed normal learning and memory retention in the Morris water maze tasks. These data support the hypothesis that galanin may have a role in functions related to mood states, including affective disorders.
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PMID:Behavioural characterisation of transgenic mice overexpressing galanin under the PDGF-B promoter. 1594 26

Galanin is a highly inducible neuropeptide, showing distinct up-regulation after pathological disturbance within the nervous system. Significant increase in galanin expression is observed after peripheral nerve injury, in the basal forebrain in Alzheimer's disease (AD), during neuronal development, and after stimulation with estrogen, while seizure activity deplete galanin in the hippocampus. A wide distribution of galanin and its receptors is seen in the nervous system, often in co-localization with classical neurotransmitters and other neuromodulators. Galanin acts predominantly as an inhibitory, hyperpolarizing neuromodulator on neurotransmitter and glucose-induced insulin release and stimulates growth hormone and prolactin secretion. Galanin has been implicated in several higher order physiological functions including cognition, feeding, nociception, mood regulation, and neuroendocrine modulation. The effects of galanin are mediated via three G protein-coupled receptors with different functional coupling. Moderate to low pharmacological effects are seen by galanin under physiological conditions, in contrast to its dramatic effects on the nervous system after neuronal disturbance. This pathophysiological heavy function of the galaninergic system renders it an interest for disorders such as AD, depression, and epilepsy in terms of side effects. Some properties of the galaninergic system are of particular importance in the context of neurodegeneration. Galanin is highly inducible, 10- to 100-fold, upon nerve injury, whereas most neuropeptides are induced 1.5- to 2-fold. Galanin is strongly neurotrophic during development as well as subsequent to injury. Whereas other neurotrophic neuropeptides like VIP and PACAP activate cAMP synthesis, galanin suppresses its synthesis, yet it is a strong neurotrophic as well as neuroprotective agent. As we delineate which galanin receptor subtype mediates neuroprotective and neurotrophic effects and which mediates synaptic inhibition, pharmacological use of receptor- selective galaninergic ligands for treatment in neurodegenerative diseases are coming closer.
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PMID:Galanin and its receptors in neurological disorders. 1605 44

The neurochemistry of feeding was a highlight of this meeting. A number of peptides are now known to participate in the control of nutrient balance, and many of them featured in the meeting, including the feeding suppressors alpha-melanocyte-stimulating hormone, leptin and corticotrophin releasing hormone, and the orexigenic agents, melanin-concentrating hormone, Agouti-related peptide, orexin A and neuropeptide Y. Other substances that play a role in feeding are amylin and its antagonist, AC-187, histamine, dopamine, serotonin, opiates, galanin and CART peptides. The hypothalamic and extrahypothalamic localization of these feedingrelated substances and their interactions with one another, and other brain regions, are beginning to be understood. Another symposium focused on sigma receptor ligands, such as (+)-pentazocine, PRE-084, the neurosteroid pregnanolone sulfate, NE-100, igmesine (JO-1784) and BD-1008 and related compounds. Results showed that sigma ligands may affect Ca(2+) signaling via two modes of action, one being at the endoplasmic reticulum and the other at the plasma membrane. Sigma receptors have been implicated in learning and memory, and may play a role in anxiety and depression.
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PMID:International Behavioral Neuroscience Society - Ninth meeting. Neurochemistry of feeding. 1608 42

The neuropeptide galanin mediates its effects through the receptor subtypes Gal(1), Gal(2), and Gal(3) and has been implicated in anxiety- and depression-related behaviors. Nevertheless, the receptor subtypes relevant to these behaviors are not known because of the lack of available galanin-selective ligands. In this article, we use behavioral, neurochemical, and electrophysiological approaches to investigate the anxiolytic- and antidepressant-like effects of two potent small-molecule, Gal(3)-selective antagonists, SNAP 37889 and the more soluble analog SNAP 398299. Acute administration of SNAP 37889 or SNAP 398299 enhanced rat social interaction. Furthermore, acute SNAP 37889 was also shown to reduce guinea pig vocalizations after maternal separation, to attenuate stress-induced hyperthermia in mice, to increase punished drinking in rats, and to decrease immobility and increase swimming time during forced swim tests with rats. Moreover, SNAP 37889 increased the social interaction time after 14 days of treatment and maintained its antidepressant effects during forced swim tests with rats after 21 days of treatment. In microdialysis studies, SNAP 37889 partially antagonized the galanin-evoked reduction in hippocampal serotonin (5-hydroxytryptamine, 5-HT), as did the 5-HT(1A) receptor antagonist WAY100635. Their combination produced a complete reversal of the effect of galanin. SNAP 398299 partially reversed the galanin-evoked inhibition of dorsal raphe cell firing and galanin-evoked hyperpolarizing currents. These results indicate that Gal(3)-selective antagonists produce anxiolytic- and antidepressant-like effects, possibly by attenuating the inhibitory influence of galanin on 5-HT transmission at the level of the dorsal raphe nucleus.
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PMID:Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. 1628 67

Galanin is a neuropeptide synthesized in many neuronal types including brainstem norepinephrine-producing cells of the locus coeruleus and the serotonin-producing neurons of the dorsal raphe nucleus. Galanin inhibits the firing of rodent norepinephrine, serotonin and dopamine neurons and reduces release of these neurotransmitters in forebrain target regions. The distribution of galanin and its receptors and its actions on monoamine signaling has fostered interest in this neuropeptide in the field of behavioral pharmacology and the potential role of galanin in the pathophysiology of neurological diseases such as Alzheimer's disease, epilepsy, stroke, and in psychiatric disorders such as anxiety, depression, and drug addiction, particularly withdrawal. In rodent models, expression of galanin in brain is altered by various stressors, while administration of galanin can modulate anxiety-like responses to stress. Emerging evidence further supports a role for galanin in the mediation of depression-related behaviors in rodents. Recently, galanin agonists have been shown to decrease behavioral signs of opiate withdrawal, which are thought to result from hyperactivation of brain stress pathways. Studies using genetically modified mice suggest that galanin normally plays a protective role against opiate reinforcement and withdrawal. The present article reviews current evidence on a potential role for galanin in modulating stress-related neural pathways and behaviors, and speculates on the therapeutic potential of targeting this galanin system for emotional disorders and opiate addiction.
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PMID:Galanin: a novel therapeutic target for depression, anxiety disorders and drug addiction? 1661 Oct 95

Galanin is a 29 amino-acid (30 in humans) neuropeptide with a close functional relationship with neurotransmitter systems implicated in the pathophysiology and treatment of depression and anxiety disorders. In rodent models of depression-related behavior, treatment with galanin or compounds with agonist actions at galanin receptors has been shown to affect depression-related behaviors and the behavioral and neurochemical effects of antidepressants. Treatment with clinically efficacious antidepressants alters galanin and galanin receptor gene expression in rodents. Rodent anxiety-like behaviors appear to be modulated by galanin in a complex manner, with studies showing either increases, decreases and no effects of galanin treatments and galanin mutations on anxiety-like behavior in various tasks. One concept to emerge from this literature is that galanin recruitment during extreme behavioral and physiological provocations such as stress and opiate withdrawal may serve to attenuate negative emotional states caused by noradrenergic hyperactivation. The specific galanin receptor subtypes mediating the anxiety- and depression-related effects of galanin remains to be determined, with evidence supporting a possible contribution of GalR1, GalR2 and GalR3. While our understanding of the role of galanin as a modulator of emotion remains at an early stage, recent progress in this rapidly evolving field raise possibility of that galanin may represent a target for the development of novel antidepressant and anxiolytic drug treatments.
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PMID:Galanin as a modulator of anxiety and depression and a therapeutic target for affective disease. 1673 16

This review summarizes recent developments in the field of sleep regulation, particularly in the role of hormones, and of synthetic GABA(A) receptor agonists. Certain hormones play a specific role in sleep regulation. A reciprocal interaction of the neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. At least in males GHRH is a common stimulus of non-rapid-eye-movement sleep (NREMS) and GH and inhibits the hypothalamo-pituitary adrenocortical (HPA) hormones, whereas CRH exerts opposite effects. Furthermore CRH may enhance rapid-eye-movement sleep (REMS). Changes in the GHRH:CRH ratio in favor of CRH appear to contribute to sleep EEG and endocrine changes during depression and normal ageing. In women, however, CRH-like effects of GHRH were found. Besides CRH somatostatin impairs sleep, whereas ghrelin, galanin and neuropeptide Y promote sleep. Vasoactive intestinal polypeptide appears to be involved in the temporal organization of human sleep. Beside of peptides, steroids participate in sleep regulation. Cortisol appears to promote REMS. Various neuroactive steroids exert specific effects on sleep. The beneficial effect of estrogen replacement therapy in menopausal women suggests a role of estrogen in sleep regulation. The GABA(A) receptor or GABAergic neurons are involved in the action of many of these hormones. Recently synthetic GABA(A) agonists, particularly gaboxadol and the GABA reuptake inhibitor tiagabine were shown to differ distinctly in their action from allosteric modulators of the GABA(A) receptor like benzodiazepines as they promote slow-wave sleep, decrease wakefulness and do not affect REMS.
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PMID:Neurochemical regulation of sleep. 1677 43


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