Long-term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co-administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus.
antidepressant
galanin receptor 2
hippocampus
intranasal administration
neurogenesis
neuronal differentiation
neuropeptide Y Y1 receptor
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
15 Apr 2024
15 Apr 2024
Historique:
revised:
27
02
2024
received:
13
01
2024
accepted:
25
03
2024
medline:
4
4
2024
pubmed:
4
4
2024
entrez:
4
4
2024
Statut:
ppublish
Résumé
This study evaluates the sustained antidepressant-like effects and neurogenic potential of a 3-day intranasal co-administration regimen of galanin receptor 2 (GALR2) agonist M1145 and neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31, Pro34]NPY in the ventral hippocampus of adult rats, with outcomes analyzed 3 weeks post-treatment. Utilizing the forced swimming test (FST), we found that this co-administration significantly enhances antidepressant-like behaviors, an effect neutralized by the GALR2 antagonist M871, highlighting the synergistic potential of these neuropeptides in modulating mood-related behaviors. In situ proximity ligation assay (PLA) indicated a significant increase in GALR2/NPYY1R heteroreceptor complexes in the ventral hippocampal dentate gyrus, suggesting a molecular basis for the behavioral outcomes observed. Moreover, proliferating cell nuclear antigen (PCNA) immunolabeling revealed increased cell proliferation in the subgranular zone of the dentate gyrus, specifically in neuroblasts as evidenced by co-labeling with doublecortin (DCX), without affecting quiescent neural progenitors or astrocytes. The study also noted a significant uptick in the number of DCX-positive cells and alterations in dendritic morphology in the ventral hippocampus, indicative of enhanced neuronal differentiation and maturation. These morphological changes highlight the potential of these agonists to facilitate the functional integration of new neurons into existing neural circuits. By demonstrating the long-lasting effects of a brief, 3-day intranasal administration of GALR2 and NPY1R agonists, our findings contribute significantly to the understanding of neuropeptide-mediated neuroplasticity and herald novel therapeutic strategies for the treatment of depression and related mood disorders, emphasizing the therapeutic promise of targeting neurogenesis and neuronal maturation processes.
Identifiants
pubmed: 38572811
doi: 10.1096/fj.202400087R
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23595Subventions
Organisme : Andalusian Board | Consejería de Salud y Consumo, Junta de Andalucía (CSC)
ID : UMA18-FEDERJA-100
Organisme : Andalusian Board | Consejería de Salud y Consumo, Junta de Andalucía (CSC)
ID : ProyExcel_00613
Organisme : Andalusian Board | Consejería de Salud y Consumo, Junta de Andalucía (CSC)
ID : EMERGIA 2020-39318
Organisme : Royal Swedish Academy of Sciences (KVA)
ID : 62X-00715-50-3
Organisme : Åhlén-stiftelsen (Åhlén Foundation)
Organisme : Hjärnfonden
ID : F02018-0286
Organisme : Hjärnfonden
ID : F02019-0296
Organisme : Ministerio de ciencia, Innovación y universidades
ID : CNS2022-136008
Informations de copyright
© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Références
World Health Organization. Front matter. Depression and Other Common Mental Disorders. World Health Organization; 2017:2.
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Akinyemiju TF, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability‐adjusted life‐years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study. JAMA Oncol. 2018;4:1553‐1568.
Catala‐Lopez F, Genova‐Maleras R, Vieta E, Tabares‐Seisdedos R. The increasing burden of mental and neurological disorders. Eur Neuropsychopharmacol. 2013;23:1337‐1339.
McEwen BS, Bowles NP, Gray JD, et al. Mechanisms of stress in the brain. Nat Neurosci. 2015;18:1353‐1363.
Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci. 2007;10:1110‐1115.
Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta‐analysis of MRI studies. Am J Psychiatry. 2004;161:1957‐1966.
MacQueen GM, Campbell S, McEwen BS, et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA. 2003;100:1387‐1392.
Warner‐Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16:239‐249.
Boldrini M, Santiago AN, Hen R, et al. Hippocampal granule neuron number and dentate gyrus volume in antidepressant‐treated and untreated major depression. Neuropsychopharmacology. 2013;38:1068‐1077.
Tanti A, Rainer Q, Minier F, Surget A, Belzung C. Differential environmental regulation of neurogenesis along the septo‐temporal axis of the hippocampus. Neuropharmacology. 2012;63:374‐384.
Lehmann ML, Brachman RA, Martinowich K, Schloesser RJ, Herkenham M. Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis. J Neurosci. 2013;33:2961‐2972.
Drew LJ, Fusi S, Hen R. Adult neurogenesis in the mammalian hippocampus: why the dentate gyrus? Learn Mem. 2013;20:710‐729.
Boldrini M, Hen R, Underwood MD, et al. Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression. Biol Psychiatry. 2012;72:562‐571.
Anacker C, Zunszain PA, Cattaneo A, et al. Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol Psychiatry. 2011;16:738‐750.
Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805‐809.
Eliwa H, Belzung C, Surget A. Adult hippocampal neurogenesis: is it the alpha and omega of antidepressant action? Biochem Pharmacol. 2017;141:86‐99.
Huang GJ, Bannerman D, Flint J. Chronic fluoxetine treatment alters behavior, but not adult hippocampal neurogenesis, in BALB/cJ mice. Mol Psychiatry. 2008;13:119‐121.
Holick KA, Lee DC, Hen R, Dulawa SC. Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor. Neuropsychopharmacology. 2008;33:406‐417.
Mahar I, Bambico FR, Mechawar N, Nobrega JN. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev. 2014;38:173‐192.
Haroon E, Miller AH, Sanacora G. Inflammation, glutamate, and glia: a trio of trouble in mood disorders. Neuropsychopharmacology. 2017;42:193‐215.
Thorsell A, Mathe AA. Neuropeptide Y in alcohol addiction and affective disorders. Front Endocrinol (Lausanne). 2017;8:178.
Kask A, Harro J, von Horsten S, Redrobe JP, Dumont Y, Quirion R. The neurocircuitry and receptor subtypes mediating anxiolytic‐like effects of neuropeptide Y. Neurosci Biobehav Rev. 2002;26:259‐283.
Kormos V, Gaszner B. Role of neuropeptides in anxiety, stress, and depression: from animals to humans. Neuropeptides. 2013;47:401‐419.
Zaben MJ, Gray WP. Neuropeptides and hippocampal neurogenesis. Neuropeptides. 2013;47:431‐438.
Reichmann F, Holzer P. Neuropeptide Y: a stressful review. Neuropeptides. 2016;55:99‐109.
Cohen H, Liu T, Kozlovsky N, Kaplan Z, Zohar J, Mathe AA. The neuropeptide Y (NPY)‐ergic system is associated with behavioral resilience to stress exposure in an animal model of post‐traumatic stress disorder. Neuropsychopharmacology. 2012;37:350‐363.
Cohen H, Vainer E, Zeev K, Zohar J, Mathe AA. Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor. Eur Neuropsychopharmacol. 2018;28:159‐170.
Jimenez‐Vasquez PA, Diaz‐Cabiale Z, Caberlotto L, et al. Electroconvulsive stimuli selectively affect behavior and neuropeptide Y (NPY) and NPY Y(1) receptor gene expressions in hippocampus and hypothalamus of Flinders sensitive line rat model of depression. Eur Neuropsychopharmacol. 2007;17:298‐308.
Redrobe JP, Dumont Y, Fournier A, Quirion R. The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY‐induced antidepressant‐like activity in the mouse forced swimming test. Neuropsychopharmacology. 2002;26:615‐624.
Goyal SN, Upadhya MA, Kokare DM, Bhisikar SM, Subhedar NK. Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: involvement of NPY Y1 receptors. Brain Res. 2009;1266:45‐53.
Katsetos CD, Del Valle L, Geddes JF, et al. Aberrant localization of the neuronal class III beta‐tubulin in astrocytomas. Arch Pathol Lab Med. 2001;125:613‐624.
O'Donnell D, Ahmad S, Wahlestedt C, Walker P. Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. J Comp Neurol. 1999;409:469‐481.
Lu X, Mazarati A, Sanna P, Shinmei S, Bartfai T. Distribution and differential regulation of galanin receptor subtypes in rat brain: effects of seizure activity. Neuropeptides. 2005;39:147‐152.
Langel U. Galanin receptor ligands. Springerplus. 2015;4:L18.
Mohd Zahir I, Ogawa S, Dominic NA, Soga T, Parhar IS. Spexin and galanin in metabolic functions and social behaviors with a focus on non‐mammalian vertebrates. Front Endocrinol (Lausanne). 2022;13:882772.
Narvaez M, Millon C, Borroto‐Escuela D, et al. Galanin receptor 2‐neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions. Brain Struct Funct. 2015;220:2289‐2301.
Narvaez M, Borroto‐Escuela DO, Millon C, et al. Galanin receptor 2‐neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant‐like effects. Brain Struct Funct. 2016;221:4129‐4139.
Narvaez M, Borroto‐Escuela DO, Santin L, et al. A novel integrative mechanism in anxiolytic behavior induced by galanin 2/neuropeptide Y Y1 receptor interactions on medial paracapsular intercalated amygdala in rats. Front Cell Neurosci. 2018;12:119.
Mirchandani‐Duque M, Barbancho MA, Lopez‐Salas A, et al. Galanin and neuropeptide Y interaction enhances proliferation of granule precursor cells and expression of neuroprotective factors in the rat hippocampus with consequent augmented spatial memory. Biomedicine. 2022;10:1297.
Borroto‐Escuela DO, Pita‐Rodriguez M, Fores‐Pons R, Barbancho MA, Fuxe K, Narvaez M. Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus. J Cell Physiol. 2021;236:3565‐3578.
Borroto‐Escuela DO, Fores R, Pita M, et al. Intranasal delivery of galanin 2 and neuropeptide Y1 agonists enhanced spatial memory performance and neuronal precursor cells proliferation in the dorsal hippocampus in rats. Front Pharmacol. 2022;13:820210.
Diaz‐Sanchez E, Lopez‐Salas A, Mirchandani‐Duque M, et al. Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion. Biomed Pharmacother. 2023;161:114433.
Alvarez‐Contino JE, Diaz‐Sanchez E, Mirchandani‐Duque M, et al. GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant‐like effects involving BDNF actions. J Cell Physiol. 2023;238(2):459‐474.
Schmidt‐Hieber C, Jonas P, Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature. 2004;429:184‐187.
Bruel‐Jungerman E, Laroche S, Rampon C. New neurons in the dentate gyrus are involved in the expression of enhanced long‐term memory following environmental enrichment. Eur J Neurosci. 2005;21:513‐521.
Snyder JS, Choe JS, Clifford MA, et al. Adult‐born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice. J Neurosci. 2009;29:14484‐14495.
Fuzesi T, Wittmann G, Liposits Z, Lechan RM, Fekete C. Contribution of noradrenergic and adrenergic cell groups of the brainstem and agouti‐related protein‐synthesizing neurons of the arcuate nucleus to neuropeptide‐y innervation of corticotropin‐releasing hormone neurons in hypothalamic paraventricular nucleus of the rat. Endocrinology. 2007;148:5442‐5450.
Gelfo F, Tirassa P, De Bartolo P, et al. NPY intraperitoneal injections produce antidepressant‐like effects and downregulate BDNF in the rat hypothalamus. CNS Neurosci Ther. 2012;18:487‐492.
Serova L, Mulhall H, Sabban E. NPY1 receptor agonist modulates development of depressive‐like behavior and gene expression in hypothalamus in SPS rodent PTSD model. Front Neurosci. 2017;11:203.
Decressac M, Wright B, David B, et al. Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis. Hippocampus. 2011;21:233‐238.
Nahvi RJ, Tanelian A, Nwokafor C, Hollander CM, Peacock L, Sabban EL. Intranasal neuropeptide Y as a potential therapeutic for depressive behavior in the rodent single prolonged stress model in females. Front Behav Neurosci. 2021;15:705579.
Corvino V, Marchese E, Podda MV, et al. The neurogenic effects of exogenous neuropeptide Y: early molecular events and long‐lasting effects in the hippocampus of trimethyltin‐treated rats. PLoS One. 2014;9:e88294.
Silveira Villarroel H, Bompolaki M, Mackay JP, et al. NPY induces stress resilience via downregulation of I(h) in principal neurons of rat basolateral amygdala. J Neurosci. 2018;38:4505‐4520.
Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266:730‐732.
Planchez B, Surget A, Belzung C. Animal models of major depression: drawbacks and challenges. J Neural Transm (Vienna). 2019;126:1383‐1408.
Yankelevitch‐Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive‐like behavior. J Vis Exp. 2015;97:52587.
Kalynchuk LE, Gregus A, Boudreau D, Perrot‐Sinal TS. Corticosterone increases depression‐like behavior, with some effects on predator odor‐induced defensive behavior, in male and female rats. Behav Neurosci. 2004;118:1365‐1377.
Morales‐Medina JC, Dumont Y, Benoit CE, et al. Role of neuropeptide Y Y(1) and Y(2) receptors on behavioral despair in a rat model of depression with co‐morbid anxiety. Neuropharmacology. 2012;62:200‐208.
Morales‐Medina JC, Juarez I, Venancio‐Garcia E, et al. Impaired structural hippocampal plasticity is associated with emotional and memory deficits in the olfactory bulbectomized rat. Neuroscience. 2013;236:233‐243.
Ribeiro ACR, Zhu J, Kronfol MM, et al. Molecular mechanisms for the antidepressant‐like effects of a low‐dose ketamine treatment in a DFP‐based rat model for Gulf War Illness. Neurotoxicology. 2020;80:52‐59.
Narváez M, Crespo‐Ramírez M, Fores‐Pons R, et al. Study of GPCR homo‐ and heteroreceptor complexes in specific neuronal cell populations using the in situ proximity ligation assay. In: Lujan R, Ciruela F, eds. Receptor and Ion Channel Detection in the Brain. Springer US; 2021:117‐134.
Cohen H, Zohar J, Kaplan Z, Arnt J. Adjunctive treatment with brexpiprazole and escitalopram reduces behavioral stress responses and increase hypothalamic NPY immunoreactivity in a rat model of PTSD‐like symptoms. Eur Neuropsychopharmacol. 2018;28:63‐74.
Wadhwa M, Prabhakar A, Ray K, et al. Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation. J Neuroinflammation. 2017;14:222.
Plumpe T, Ehninger D, Steiner B, et al. Variability of doublecortin‐associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci. 2006;7:77.
Ramirez‐Rodriguez G, Ortiz‐Lopez L, Dominguez‐Alonso A, Benitez‐King GA, Kempermann G. Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. J Pineal Res. 2011;50:29‐37.
Yagi S, Splinter JEJ, Tai D, Wong S, Wen Y, Galea LAM. Sex differences in maturation and attrition of adult neurogenesis in the hippocampus. eNeuro. 2020;7:ENEURO.0468‐19.2020.
Striepens N, Kendrick KM, Hanking V, et al. Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Sci Rep. 2013;3:3440.
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69:29‐38.
Kageyama H, Shiba K, Hirako S, et al. Anti‐obesity effect of intranasal administration of galanin‐like peptide (GALP) in obese mice. Sci Rep. 2016;6:28200.
Mathe AA, Michaneck M, Berg E, Charney DS, Murrough JW. A randomized controlled trial of intranasal neuropeptide Y in patients with major depressive disorder. Int J Neuropsychopharmacol. 2020;23:783‐790.
Sasaki‐Hamada S, Nakamura R, Nakao Y, et al. Antidepressant‐like effects exerted by the intranasal administration of a glucagon‐like peptide‐2 derivative containing cell‐penetrating peptides and a penetration‐accelerating sequence in mice. Peptides. 2017;87:64‐70.
Langmia IM, Just KS, Yamoune S, Muller JP, Stingl JC. Pharmacogenetic and drug interaction aspects on ketamine safety in its use as antidepressant—implications for precision dosing in a global perspective. Br J Clin Pharmacol. 2022;88:5149‐5165.
Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004;38:213‐224.
Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci. 2003;24:580‐588.
Polis AJ, Fitzgerald PJ, Hale PJ, Watson BO. Rodent ketamine depression‐related research: finding patterns in a literature of variability. Behav Brain Res. 2019;376:112153.
Yun S, Reyes‐Alcaraz A, Lee YN, et al. Spexin‐based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight. Front Neurosci. 2019;13:391.
Sabban EL, Serova LI. Potential of intranasal neuropeptide Y (NPY) and/or melanocortin 4 receptor (MC4R) antagonists for preventing or treating PTSD. Mil Med. 2018;183:408‐412.
Borroto‐Escuela DO, Romero‐Fernandez W, Mudo G, et al. Fibroblast growth factor receptor 1‐5‐hydroxytryptamine 1A heteroreceptor complexes and their enhancement of hippocampal plasticity. Biol Psychiatry. 2012;71:84‐91.
Narvaez M, Andrade‐Talavera Y, Valladolid‐Acebes I, et al. Existence of FGFR1‐5‐HT1AR heteroreceptor complexes in hippocampal astrocytes. Putative link to 5‐HT and FGF2 modulation of hippocampal gamma oscillations. Neuropharmacology. 2020;170:108070.
Howell OW, Scharfman HE, Herzog H, Sundstrom LE, Beck‐Sickinger A, Gray WP. Neuropeptide Y is neuroproliferative for post‐natal hippocampal precursor cells. J Neurochem. 2003;86:646‐659.
Howell OW, Doyle K, Goodman JH, et al. Neuropeptide Y stimulates neuronal precursor proliferation in the post‐natal and adult dentate gyrus. J Neurochem. 2005;93:560‐570.
Deuel TA, Liu JS, Corbo JC, Yoo SY, Rorke‐Adams LB, Walsh CA. Genetic interactions between doublecortin and doublecortin‐like kinase in neuronal migration and axon outgrowth. Neuron. 2006;49:41‐53.
Nacher J, Crespo C, McEwen BS. Doublecortin expression in the adult rat telencephalon. Eur J Neurosci. 2001;14:629‐644.
Brandt MD, Jessberger S, Steiner B, et al. Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Mol Cell Neurosci. 2003;24:603‐613.
Steiner B, Kronenberg G, Jessberger S, Brandt MD, Reuter K, Kempermann G. Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice. Glia. 2004;46:41‐52.
Wang JW, David DJ, Monckton JE, Battaglia F, Hen R. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult‐born hippocampal granule cells. J Neurosci. 2008;28:1374‐1384.
Guirado R, Sanchez‐Matarredona D, Varea E, Crespo C, Blasco‐Ibanez JM, Nacher J. Chronic fluoxetine treatment in middle‐aged rats induces changes in the expression of plasticity‐related molecules and in neurogenesis. BMC Neurosci. 2012;13:5.
Heilig M, Soderpalm B, Engel JA, Widerlov E. Centrally administered neuropeptide Y (NPY) produces anxiolytic‐like effects in animal anxiety models. Psychopharmacology. 1989;98:524‐529.
Redrobe JP, Dumont Y, Fournier A, Baker GB, Quirion R. Role of serotonin (5‐HT) in the antidepressant‐like properties of neuropeptide Y (NPY) in the mouse forced swim test. Peptides. 2005;26:1394‐1400.