Dorsal hippocampal galanin modulates anxiety-like behaviours in rats

Funck, Vinícius Rafael; Fracalossi, Maria Paula; Vidigal, A.P.P.; Beijamini, Vanessa

doi:10.1016/j.brainres.2018.02.036

Cited by 12 publications

(6 citation statements)

References 73 publications

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“…Furthermore, in the future it would be of interest to assess the comparative behavioral and neurochemical effects of chronic RXFP3 activation in the dorsal hippocampus, as this region also receives a topographic relaxin‐3 innervation and expresses RXFP3 (Ma & Gundlach, ; Ma et al, ; Tanaka et al, ), and different amino acid, monoamine, and peptide transmitters have been implicated in the control of anxiety via actions in this area in several earlier and recent investigations (see e.g., File, Kenny, & Cheeta, ; Funck, Fracalossi, Vidigal, & Beijamini, ; Gunther, Luczak, Gruteser, Abel, & Baumann, ; McEown & Treit, ; Solati, Zarrindast, & Salari, ).…”

Section: Discussionmentioning

confidence: 99%

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

et al. 2019

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Anxiety disorders are highly prevalent in modern society and better treatments are required. Key brain areas and signaling systems underlying anxiety include prefrontal cortex, hippocampus, and amygdala, and monoaminergic and peptidergic systems, respectively. Hindbrain GABAergic projection neurons that express the peptide, relaxin‐3, broadly innervate the forebrain, particularly the septum and hippocampus, and relaxin‐3 acts via a Gi/o‐protein‐coupled receptor known as the relaxin‐family peptide 3 receptor (RXFP3). Thus, relaxin‐3/RXFP3 signaling is implicated in modulation of arousal, motivation, mood, memory, and anxiety. Ventral hippocampus (vHip) is central to affective and cognitive processing and displays a high density of relaxin‐3‐positive nerve fibers and RXFP3 binding sites, but the identity of target neurons and associated effects on behavior are unknown. Therefore, in adult, male rats, we assessed the neurochemical nature of hippocampal RXFP3 mRNA‐expressing neurons and anxiety‐like and social behavior following chronic RXFP3 activation in vHip by viral vector expression of an RXFP3‐selective agonist peptide, R3/I5. RXFP3 mRNA detected by fluorescent in situ hybridization was topographically distributed across the hippocampus in somatostatin‐ and parvalbumin‐mRNA expressing GABA neurons. Chronic RXFP3 activation in vHip increased anxiety‐like behavior in the light–dark box and elevated‐plus maze, but not the large open‐field test, and reduced social interaction with a conspecific stranger. Our data reveal disruptive effects of persistent RXFP3 signaling on hippocampal GABA networks important in anxiety; and identify a potential therapeutic target for anxiety disorders that warrants further investigation in relevant preclinical models.

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Section: Discussionmentioning

confidence: 99%

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

et al. 2019

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“…It is therefore proposed that after electrical stimulation of the injured median nerve, the induced expression of c-Fos in the CN thalamic projection neurons may exert an ascending influence on the thalamus for propagating the neuropathic pain signals. Taken together, injection of AR-M1896, via binding to GalR2, activates the G q/11 and subsequent Ca 2+ -phospholipase C-dependent protein kinase C pathway [ 48 , 50 ], which may lead to NPY and/or galanin release from primary afferent terminals and c-Fos expression in the thalamic projection neurons of the CN following electrical stimulation of the injured median nerve, and then provide the ascending thalamic transmission of neuropathic pain signals. On the contrary, application of M871, which competes with galanin for binding to GalR2 [ 27 , 51 ], intercepts the above signal transduction cascade.…”

Section: Discussionmentioning

confidence: 99%

Elevated galanin receptor type 2 primarily contributes to mechanical hypersensitivity after median nerve injury

et al. 2018

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In this study, we investigated temporal changes in galanin receptor type 2 (GalR2) expression in NF200-, galanin-, neuropeptide Y (NPY)-, and neuronal nitric oxide synthase (nNOS)-like immunoreactive (LI) dorsal root ganglion (DRG) neurons after median nerve chronic constriction injury (CCI), and the effects of GalR2 on c-Fos expression in the cuneate nucleus (CN). Double immunofluorescence labeling methods were used to appraise changes in GalR2 expression in NF200-LI, galanin-LI, NPY-LI, and nNOS-LI DRG neurons after CCI. The von Frey assay was used to assess the efficiency of intraplantar administration of saline, M871 (a GalR2 antagonist), or AR-M1896 (a GalR2 agonist) on neuropathic signs of rats with CCI. The effects of alterations in c-Fos expression were assessed in all treatments. The percentage of GalR2-LI neurons in lesioned DRGs increased and peaked at 1 week after CCI. We further detected that percentages of GalR2-LI neurons labeled for NF200, galanin, NPY, and nNOS significantly increased following CCI. Furthermore, M871 remarkably attenuated tactile allodynia, but the sensation was slightly aggravated by AR-M1896 after CCI. Consequentially, after electrical stimulation of the CCI-treated median nerve, the number of c-Fos-LI neurons in the cuneate nucleus (CN) was significantly reduced in the M871 group, whereas it increased in the AR-M1896 group. These results suggest that activation of GalR2, probably through NPY or nitric oxide, induces c-Fos expression in the CN and transmits mechanical allodynia sensations to the thalamus.

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“…GAL treatment reduces serotonin release into the ventral hippocampus, and receptor antagonist treatment blocks this effect ( 10 ). Similarly, pre-treatment with a GALR2 antagonist blocked the anxiogenic effects of GAL administration into the dorsal hippocampal area ( 111 ). It is likely that GAL affects serotonin synthesis, as GAL significantly reduces the mRNA expression of tryptophan hydroxylase in the dorsal raphe nucleus ( 10 ).…”

Section: Physiological Functions Of Spx and Galmentioning

confidence: 99%

Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates

et al. 2022

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Spexin (SPX) and galanin (GAL) are two neuropeptides that are phylogenetically related and have descended from a common ancestral gene. Considerable attention has been given to these two multifunctional neuropeptides because they share GAL receptors 1,2, and 3. Since GAL and SPX-synthesizing neurons have been detected in several brain areas, therefore, it can be speculated that SPX and GAL are involved in various neurophysiological functions. Several studies have shown the functions of these two neuropeptides in energy regulation, reproduction, and response to stress. SPX acts as a satiety factor to suppress food intake, while GAL has the opposite effect as an orexigenic factor. There is evidence that SPX acts as an inhibitor of reproductive functions by suppressing gonadotropin release, while GAL modulates the activity of gonadotropin-releasing hormone (GnRH) neurons in the brain and gonadotropic cells in the pituitary. SPX and GAL are responsive to stress. Furthermore, SPX can act as an anxiolytic factor, while GAL exerts anti-depressant and pro-depressive effects depending on the receptor it binds. This review describes evidence supporting the central roles of SPX and GAL neuropeptides in energy balance, reproduction, stress, and social behaviors, with a particular focus on non-mammalian vertebrate systems.

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Dorsal hippocampal galanin modulates anxiety-like behaviours in rats

Cited by 12 publications

References 73 publications

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

Elevated galanin receptor type 2 primarily contributes to mechanical hypersensitivity after median nerve injury

Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates

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