Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions

Narváez, Manuel; Millón, Carmelo; Borroto-Escuela, Dasiel O.; Flores-Burgess, Antonio; Santín, Luis J.; Parrado, Concepción; Gago, Belén; Puigcerver, Araceli; Narváez, José Ángel; Dı́az-Cabiale, Zaida

doi:10.1007/s00429-014-0788-7

Cited by 30 publications

(53 citation statements)

References 39 publications

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“…In the open field, in agreement with other authors ( Narvaez et al, 2014 ) the dose of 3 nmol of GAL did not affect the time spent in and number of entries into the central square in the open field ( Figure 2C and D ). In view of the fact that GAL(1–15) at 3 nmol significantly decreased the time ( t = 2.318, p < 0.05, df = 13) and number ( t = 3.379, p < 0.01, df = 16) of entries in the open field, our results indicate than only GAL(1–15) and not GAL modifies the anxiety parameters in the present model.…”

Section: Resultssupporting

confidence: 93%

“…After each trial, all surfaces were cleaned with a paper towel and 70% ethanol solution. For the open-field (100 x 100 x 50cm), total time spent in and entries into the inner square were recorded ( Grivas et al, 2013 ; Narvaez et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…The procedures have been previously used ( Narváez et al, 2014 ) . Primary antibody rabbit anti-GAL 2 receptor (Alomone Lab, 1/250) was incubated for 12 hours at 4ºC and detected with the red secondary antibody mouse anti-rabbit DyLight 549 (Jackson inmunoResearch Laboratories, 1/100).…”

Section: Methodsmentioning

confidence: 99%

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A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

Millón

Flores-Burgess

Narváez

et al. 2015

International Journal of Neuropsychopharmacology

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110

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Background:Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1–15)] in anxiety- and depression-related behavioral tests in rats.Methods:The effect of GAL(1–15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1–15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1–15) were also studied in the cell line RN33B.Results:GAL(1–15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1–15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1–15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1–15) decreased 5-HT immunoreactivity more strongly than GAL.Conclusions:Our results indicate that GAL(1–15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety.

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Section: Resultssupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

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A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

Millón

Flores-Burgess

Narváez

et al. 2015

International Journal of Neuropsychopharmacology

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110

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“…Certain neuropeptide systems participate in the behaviors associated with anxiety. It has been shown that long-term dysregulation of these systems contributes to the development of anxiety disorders, including PTSD [9, 10]. …”

Section: Introductionmentioning

confidence: 99%

“…There is evidence that Galanin (Gal) and its three general receptor subtypes known as GalR1, GalR2 and Gal R3, play a significant role in anxiety, depression, and stress-like behaviors through modulation of neuroendocrine, serotonergic and noradrenergic systems [10–13]There are also reports suggesting that Gal has antidepressant effects[14] [15]…”

Section: Introductionmentioning

confidence: 99%

Changes in Galanin Systems in a Rat Model of Post-Traumatic Stress Disorder (PTSD)

et al. 2016

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Post-traumatic stress disorder (PTSD) is a chronic syndrome triggered by exposure to trauma and a failure to recover from a normal negative emotional reaction to traumatic stress. The neurobiology of PTSD and the participation of neuropeptides in the neural systems and circuits that control fear and anxiety are not fully understood. The long-term dysregulation of neuropeptide systems contributes to the development of anxiety disorders, including PTSD. The neuropeptide galanin (Gal) and its receptors participate in anxiety-like and depression-related behaviors via the modulation of neuroendocrine and monoaminergic systems. The objective of this research was to investigate how Gal expression changes in the brain of rats 2 weeks after exposure to footshock. Rats exposed to footshocks were subdivided into high responders (HR; immobility>60%) and low responders (LR; immobility<40%) based on immobility elicited by a novel tone one day after exposure. On day 14, rats were anesthetized, and the amygdala, hypothalamus, pituitary and adrenal glands were removed for analysis using real-time polymerase chain reaction (RT-PCR). Gal mRNA levels were increased in the amygdala and hypothalamus of HR compared with the control and LR. In contrast, Gal mRNA levels were decreased in the adrenal and pituitary glands of HR compared with the control and LR. Thus, the differential regulation (dysregulation) of the neuropeptide Gal in these tissues may contribute to anxiety and PTSD development.

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Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

Borroto-Escuela

Pita-Rodríguez

Fores-Pons

et al. 2020

Journal Cellular Physiology

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A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5‐Bromo‐2'‐deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG). We employed in situ proximity ligation assay to manifest GALR2/NPYY1R heteroreceptor complexes. Additionally, the expression pattern of GALR2 and the activation of the extracellular‐regulated kinases (ERK) pathway after GALR2 and NPYY1R costimulation in cell cultures were examined. GALR2 and NPYY1R coactivation resulted in sustained antidepressant behaviors in the FST after 24 h, linked to increased cell proliferation in the vDG. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was observed in vDG, on doublecortin‐expressing neuroblasts. Recruitment of the GALR2 expression to the plasma membrane was observed upon the coactivation of GALR2 and NPYY1R in cell cultures, presumably associated to the enhanced effects on the activation of ERK pathway. GALR2 may promote the GALR2/NPYY1R heteroreceptor complexes formation in the ventral hippocampus. It may induce a transformation of cell proliferation toward a neuronal lineage by enhancement of ERK pathway. Thus, it may give the mechanism for the antidepressant behavior observed. These results may provide the basis for the development of heterobivalent agonist pharmacophores, targeting GALR2/NPYY1R heteromers, especially in the neuronal precursor cells of the dentate gyrus in the ventral hippocampus for the novel treatment of depression.

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Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions

Cited by 30 publications

References 39 publications

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

Changes in Galanin Systems in a Rat Model of Post-Traumatic Stress Disorder (PTSD)

Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus

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