Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

He, Ben; Counts, Scott; Pérez, Silvia E.; Hohmann, John G.; Koprich, James B.; Lipton, Jack W.; Steiner, Robert A.; Crawley, Jacqueline N.; Mufson, Elliott J.

doi:10.1016/j.neuroscience.2005.01.068

Cited by 31 publications

(25 citation statements)

References 48 publications

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“…First, among the three galanin receptors that are distributed in the central nervous system, GalR1 subtype predominates and accounts for approximately 90% of all 125 I-galanin-binding sites in the PVN, with the residual 10% being either GalR2 or GalR3 [32,33] . In addition, the expression of GalR1 mRNA is positively correlated with galanin level, but there is no such correlation with GalR2 or GalR3 expression in the hypothalamic nuclei of galanin transgenic mice [34] . Second, GalR1 knockout (GalR1-KO) mice show abnormal adaptation to dietary challenges under high-fat and high-glucose conditions, while showing normal regulation with chow diets [35][36][37] .…”

Section: Effects Of Galanin On Food Intake and Energy Expenditurementioning

confidence: 89%

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Fang

et al. 2011

Neurosci. Bull.

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Abstract:Galanin is a neuropeptide widely expressed in the brain. It is implicated in energy expenditure, feeding, and the regulation of body weight. Numerous studies have revealed that galanin regulates food intake via galanin receptors, 5-HT 1A receptor and adrenergic α-2 receptor. In this review, we summarize recent findings that reveal the essential role of galanin in increasing food intake as well as body weight and that identify the individual galanin receptor subtypes involved in the brain's modulation of food intake and energy expenditure, to provide a theoretical basis for further studies of different aspects of galanin action.

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Section: Effects Of Galanin On Food Intake and Energy Expenditurementioning

confidence: 89%

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Fang

et al. 2011

Neurosci. Bull.

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“…Furthermore, nonspecific effects of SNAP 37889 cannot be excluded. In the mouse brain, GAL 3 receptor mRNA and protein are prominently expressed in the periaqueductal gray, thalamus, hypothalamus, amygdala, hippocampal formation, and prefrontal cortex (10,11), which are brain areas that play an important role in emotional regulation and stress sensitivity. It is likely that GAL modulates stress and anxiety through GAL 3 receptors located in the hypothalamus, either by directly modulating neuronal circuitries involving the amygdala, hippocampus, raphe nucleus, and locus coeruleus or by interfering with the hypothalamic-pituitary-adrenal axis (33).…”

Section: Discussionmentioning

confidence: 99%

“…GAL 1 receptor is additionally expressed in the brainstem (medulla oblongata and lateral parabrachial nucleus) and in the dorsal horn of the spinal cord, and GAL 2 receptor expression is further found in the cerebral cortex, cerebellum, and spinal cord. Expression of GAL 3 receptor in the CNS is more limited, with mRNA being preferably detected in the hypothalamus (10,11). This differential localization of the three GAL receptors in the brain, as determined by in situ hybridization, suggests that different functions of GAL might be mediated by individual receptor subtypes.…”

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confidence: 99%

GAL ₃ receptor KO mice exhibit an anxiety-like phenotype

Brunner¹,

Farzi

Locker³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL 1-3 receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL 1 and GAL 2 receptors in anxiety-and depression-related behavior. However, to date, there is sparse literature implicating GAL 3 receptors in behavioral functions. Therefore, we studied the behavior of GAL 3 receptor-deficient (GAL 3 -KO) mice to elucidate whether GAL 3 receptors are involved in mediating behavior-associated actions of GAL. The GAL 3 -KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL 3 -KO mice exhibited an anxietylike phenotype in the elevated plus maze, open field, and light/ dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL 3 receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders.T hirty years ago, Tatemoto et al. (1) isolated the neuropeptide galanin (GAL), a 29-aa (30-aa in humans) peptide, from porcine intestine. The peptide is highly conserved throughout evolution and found in many other species. GAL is widely distributed in the CNS and peripheral nervous system, and it has a variety of biological and physiological functions, ranging from energy homeostasis, reproduction, and feeding to cognition and learning (2). In the murine brain, GAL mRNA is extensively expressed in the hypothalamic and brainstem areas. The highest expression levels were observed in the preoptic, periventricular, and dorsomedial hypothalamic nuclei; bed nucleus of the stria terminalis (BNST); medial and lateral amygdala; locus coeruleus; and nucleus of the solitary tract (3). Furthermore, GAL coexists with the serotonin and norepinephrine systems in the rodent brain and acts as an inhibitory neuromodulator of norepinephrine, serotonin, dopamine, glutamate, and acetylcholine function (4). The expression pattern and neuromodulatory functions of GAL suggest a role for this neuropeptide in mood disorders like anxiety and depression. Accordingly, administration of GAL via the intracerebroventricular (i.c.v.) route or into the dopaminergic ventral tegmental area induced depression-like behavior in the rat forced swim test (FST) (5, 6). Several studies in GAL-overexpressing transgenic mice reported an increased depression-like behavior in the FST (7, 8) but found no differences in anxiety-related behavior und...

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“…Jacoby and coworkers (2002) demonstrated normal GalR2 receptor levels in GalR1 null mutant mice, suggesting that functional loss of one receptor may not trigger compensatory changes in other receptor levels. In contrast, mice chronically overexpressing galanin (Gal-tg) display increased GalR1 mRNA levels in the CA1 region of the hippocampus while levels of GalR2 and GalR3 mRNA were unchanged (He et al, 2005). One way to further test for compensatory interactions between GalR1 and GalR2 is to generate double knockouts deficient in both of these receptor subtypes.…”

Section: Discussionmentioning

confidence: 99%

Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze

Bailey

Pavlova²,

Rohde³

et al. 2007

Pharmacology Biochemistry and Behavior

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The neuropeptide galanin has been implicated in anxiety-related behaviors, cognition, analgesia, and feeding in rodents. Neuromodulatory actions of galanin are mediated by three G-protein coupled receptors, GalR1, GalR2, and GalR3. The present study investigates the role of the GalR2 receptor by evaluating behavioral phenotypes of mice with a targeted mutation in the GalR2 gene. A threetiered behavioral phenotyping approach first examined control measures of general health, body weight, neurological reflexes, sensory abilities and motor function. Mice were then assessed on several tests for cognitive and anxiety-like behaviors. GalR2 null mutants and heterozygotes were not significantly different from wildtype littermates on two cognitive tests previously shown to be sensitive to galanin manipulation: acquisition of the Morris water maze spatial task, and trace cued and contextual fear conditioning, an emotional learning and memory task. Two independent cohorts of GalR2 null mutant mice demonstrated an anxiogenic-like phenotype in the elevated plus-maze. No genotype differences were detected on several other measures of anxiety-like behavior. The discovery of an anxiogenic phenotype specific to the elevated plus-maze, similar to findings in GalR1 null mutants, highlights the potential therapeutic efficacy of targeting GalR1 and GalR2 receptors in treating anxiety disorders. Keywords galanin; GalR2 null mutant; anxiogenic-like; mice; learning; memory; nociception; neuropeptide Converging evidence from many laboratories implicates galanin and galanin receptors in anxiety-like and depression-related behaviors, via modulation of neuroendocrine and noradrenergic systems (Barrera et al., 2005;Echevarria et al., 2005;Holmes et al., 2002Holmes et al., , 2003 Khoshbouei et al., 2002a,b). Rats administered galanin intracerebroventricularly (ICV) showed a significant increase in punished responding in the Vogel punished drinking test (Bing et al., 1993). Conversely, intra-amygdala administration of galanin produced a dose dependent decrease in punished drinking without affecting unpunished drinking or behavior in a second conflict-based test, the elevated plus-maze (Möller et al., 1999). Restraint stress in rats induced anxiogenic-like behavior in a social recognition task and in the elevated plus-maze

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Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Cited by 31 publications

References 48 publications

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

GAL ₃ receptor KO mice exhibit an anxiety-like phenotype

Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze

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Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Cited by 31 publications

References 48 publications

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

GAL 3 receptor KO mice exhibit an anxiety-like phenotype

Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze

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GAL ₃ receptor KO mice exhibit an anxiety-like phenotype