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Neurological Sciences

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22.11.2020 | Original Article

GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner

verfasst von: Taylor S. Trammell, Natalie L. Henderson, Haley S. Madkour, Gregg D. Stanwood, Devon L. Graham

Erschienen in: Neurological Sciences | Ausgabe 7/2021

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Abstract

Rationale

The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been purported to have antidepressant-like and cognitive-enhancing effects. Many people suffering from major depressive disorder (MDD) also experience deficits in cognition. While currently approved antidepressant pharmacotherapies can alleviate the mood symptoms in some patients, they do not treat the cognitive ones.

Objectives

We tested whether systemic administration of a GLP-1R agonist would alter location discrimination, a cognitive task that is diminished in humans with MDD.

Methods

Male and female laboratory mice (6–8 weeks old, N = 6–14/sex) were trained in a touchscreen operant task of location discrimination. Upon reaching baseline criterion, mice were administered vehicle or a GLP-1R agonist, Exendin-4, systemically prior to testing in probe trials of varying difficulty.

Results

Following GLP-1R activation, males showed modest yet non-significant performance in the location discrimination task. Females, however, showed enhanced performance during the most difficult probe tests following Exendin-4 administration.

Conclusions

GLP-1R activation appears to enhance overall performance in the location discrimination task and does so in a sex- and difficulty-dependent manner. These preliminary yet impactful data indicate that GLP-1R agonists may be useful as an adjunctive pharmacotherapy to treat cognitive deficits associated with MDD and/or multiple neurological disorders.

Dickson SL, Shirazi RH, Hansson C, Bergquist F, Nissbrandt H, Skibicka KP (2012) The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors. J Neurosci 32(14):4812–4820. https://doi.org/10.1523/JNEUROSCI.6326-11.2012CrossRefPubMedPubMedCentral

Egecioglu E, Steensland P, Fredriksson I, Feltmann K, Engel JA, Jerlhag E (2013) The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents. Psychoneuroendocrinology 38(8):1259–1270. https://doi.org/10.1016/j.psyneuen.2012.11.009CrossRefPubMed

Graham DL, Erreger K, Galli A, Stanwood GD (2013) GLP-1 analog attenuates cocaine reward. Mol Psychiatry 18(9):961–962. https://doi.org/10.1038/mp.2012.141CrossRefPubMed

Tweedie D, Rachmany L, Rubovitch V, Lehrmann E, Zhang Y, Becker KG, Perez E, Miller J, Hoffer BJ, Greig NH, Pick CG (2013) Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice. Exp Neurol 239:170–182. https://doi.org/10.1016/j.expneurol.2012.10.001CrossRefPubMed

During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN (2003) Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 9(9):1173–1179. https://doi.org/10.1038/nm919CrossRefPubMed

Huang HJ, Chen YH, Liang KC, Jheng YS, Jhao JJ, Su MT, Lee-Chen GJ, Hsieh-Li HM (2012) Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection. PLoS One 7(7):e39656. https://doi.org/10.1371/journal.pone.0039656CrossRefPubMedPubMedCentral

Bhalla RK, Butters MA, Mulsant BH, Begley AE, Zmuda MD, Schoderbek B, Pollock BG, Reynolds CF 3rd, Becker JT (2006) Persistence of neuropsychologic deficits in the remitted state of late-life depression. Am J Geriatr Psychiatry 14(5):419–427. https://doi.org/10.1097/01.JGP.0000203130.45421.69CrossRefPubMed

Weitz ES, Hollon SD, Twisk J, van Straten A, Huibers MJ, David D, DeRubeis RJ, Dimidjian S, Dunlop BW, Cristea IA, Faramarzi M, Hegerl U, Jarrett RB, Kheirkhah F, Kennedy SH, Mergl R, Miranda J, Mohr DC, Rush AJ, Segal ZV, Siddique J, Simons AD, Vittengl JR, Cuijpers P (2015) Baseline depression severity as moderator of depression outcomes between cognitive behavioral therapy vs pharmacotherapy: an individual patient data meta-analysis. JAMA Psychiatry 72(11):1102–1109. https://doi.org/10.1001/jamapsychiatry.2015.1516CrossRefPubMed

McDermott LM, Ebmeier KP (2009) A meta-analysis of depression severity and cognitive function. J Affect Disord 119(1–3):1–8. https://doi.org/10.1016/j.jad.2009.04.022CrossRefPubMed

10.

Shilyansky C, Williams LM, Gyurak A, Harris A, Usherwood T, Etkin A (2016) Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. Lancet Psychiatry 3(5):425–435. https://doi.org/10.1016/S2215-0366(16)00012-2CrossRefPubMedPubMedCentral

11.

Isacson R, Nielsen E, Dannaeus K, Bertilsson G, Patrone C, Zachrisson O, Wikstrom L (2011) The glucagon-like peptide 1 receptor agonist exendin-4 improves reference memory performance and decreases immobility in the forced swim test. Eur J Pharmacol 650(1):249–255. https://doi.org/10.1016/j.ejphar.2010.10.008CrossRefPubMed

12.

Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, Kortesmaa J, Mercer A, Nielsen E, Ronnholm H, Wikstrom L (2008) Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson’s disease. J Neurosci Res 86(2):326–338. https://doi.org/10.1002/jnr.21483CrossRefPubMed

13.

Hunter K, Holscher C (2012) Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 13:33. https://doi.org/10.1186/1471-2202-13-33CrossRefPubMedPubMedCentral

14.

Moller C, Sommer W, Thorsell A, Rimondini R, Heilig M (2002) Anxiogenic-like action of centrally administered glucagon-like peptide-1 in a punished drinking test. Prog Neuro-Psychopharmacol Biol Psychiatry 26(1):119–122CrossRef

15.

Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10(6):434–445. https://doi.org/10.1038/nrn2639CrossRefPubMed

16.

Chaves Filho AJM, Cunha NL, de Souza AG, Soares MV, Juca PM, de Queiroz T, Oliveira JVS, Valvassori SS, Barichello T, Quevedo J, de Lucena D, Macedo DS (2020) The GLP-1 receptor agonist liraglutide reverses mania-like alterations and memory deficits induced by D-amphetamine and augments lithium effects in mice: relevance for bipolar disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 99:109872. https://doi.org/10.1016/j.pnpbp.2020.109872CrossRef

17.

Bierman EJ, Comijs HC, Jonker C, Beekman AT (2005) Effects of anxiety versus depression on cognition in later life. Am J Geriatr Psychiatry 13(8):686–693. https://doi.org/10.1176/appi.ajgp.13.8.686CrossRefPubMed

18.

Greenberg DL, Rice HJ, Cooper JJ, Cabeza R, Rubin DC, Labar KS (2005) Co-activation of the amygdala, hippocampus and inferior frontal gyrus during autobiographical memory retrieval. Neuropsychologia 43(5):659–674. https://doi.org/10.1016/j.neuropsychologia.2004.09.002CrossRefPubMed

19.

Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325(5937):210–213. https://doi.org/10.1126/science.1173215CrossRefPubMedPubMedCentral

20.

Yassa MA, Stark CE (2011) Pattern separation in the hippocampus. Trends Neurosci 34(10):515–525. https://doi.org/10.1016/j.tins.2011.06.006CrossRefPubMedPubMedCentral

21.

Fujii T, Saito DN, Yanaka HT, Kosaka H, Okazawa H (2014) Depressive mood modulates the anterior lateral CA1 and DG/CA3 during a pattern separation task in cognitively intact individuals: a functional MRI study. Hippocampus 24(2):214–224. https://doi.org/10.1002/hipo.22216CrossRefPubMed

22.

Graham DL, Durai HH, Trammell T, Noble BL, Mortlock DP, Galli A, Stanwood GD (2020) A novel mouse model of glucagon-like peptide-1 receptor expression: a look at the brain. J Comp Neurol 528:2445–2470. https://doi.org/10.1002/cne.24905CrossRefPubMedPubMedCentral

23.

Oomen CA, Hvoslef-Eide M, Heath CJ, Mar AC, Horner AE, Bussey TJ, Saksida LM (2013) The touchscreen operant platform for testing working memory and pattern separation in rats and mice. Nat Protoc 8(10):2006–2021. https://doi.org/10.1038/nprot.2013.124CrossRefPubMedPubMedCentral

24.

Rock PL, Roiser JP, Riedel WJ, Blackwell AD (2014) Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med 44(10):2029–2040. https://doi.org/10.1017/S0033291713002535CrossRefPubMed

25.

Ledford H (2016) Drugmakers target depression’s cognitive fog. Nature 530(7588):17. https://doi.org/10.1038/530017aCrossRefPubMed

26.

Yagi S, Galea LAM (2019) Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology 44(1):200–213. https://doi.org/10.1038/s41386-018-0208-4CrossRefPubMed

27.

Jonasson Z (2005) Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data. Neurosci Biobehav Rev 28(8):811–825. https://doi.org/10.1016/j.neubiorev.2004.10.006CrossRefPubMed

28.

Yagi S, Chow C, Lieblich SE, Galea LA (2016) Sex and strategy use matters for pattern separation, adult neurogenesis, and immediate early gene expression in the hippocampus. Hippocampus 26(1):87–101. https://doi.org/10.1002/hipo.22493CrossRefPubMed

29.

Park J, Shin GI, Park YM, Kim IY, Jang DP (2017) Sex differences of cognitive load effects on object-location binding memory. Biomed Eng Lett 7(4):305–309. https://doi.org/10.1007/s13534-017-0038-zCrossRefPubMedPubMedCentral

30.

Tanapat P, Hastings NB, Reeves AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19(14):5792–5801CrossRefPubMedPubMedCentral

31.

Lagace DC, Fischer SJ, Eisch AJ (2007) Gender and endogenous levels of estradiol do not influence adult hippocampal neurogenesis in mice. Hippocampus 17(3):175–180. https://doi.org/10.1002/hipo.20265CrossRefPubMed

32.

Tzeng WY, Chen LH, Cherng CG, Tsai YN, Yu L (2014) Sex differences and the modulating effects of gonadal hormones on basal and the stressor-decreased newly proliferative cells and neuroblasts in dentate gyrus. Psychoneuroendocrinology 42:24–37. https://doi.org/10.1016/j.psyneuen.2014.01.003CrossRefPubMed

33.

Bangasser DA, Eck SR, Telenson AM, Salvatore M (2018) Sex differences in stress regulation of arousal and cognition. Physiol Behav 187:42–50. https://doi.org/10.1016/j.physbeh.2017.09.025CrossRefPubMed

34.

Rajab E, Alqanbar B, Naiser MJ, Abdulla HA, Al-Momen MM, Kamal A (2014) Sex differences in learning and memory following short-term dietary restriction in the rat. Int J Dev Neurosci 36:74–80. https://doi.org/10.1016/j.ijdevneu.2014.05.011CrossRefPubMed

35.

Erreger K, Davis AR, Poe AM, Greig NH, Stanwood GD, Galli A (2012) Exendin-4 decreases amphetamine-induced locomotor activity. Physiol Behav 106(4):574–578. https://doi.org/10.1016/j.physbeh.2012.03.014CrossRefPubMedPubMedCentral

36.

Knauf C, Cani PD, Ait-Belgnaoui A, Benani A, Dray C, Cabou C, Colom A, Uldry M, Rastrelli S, Sabatier E, Godet N, Waget A, Penicaud L, Valet P, Burcelin R (2008) Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure. Endocrinology 149(10):4768–4777. https://doi.org/10.1210/en.2008-0180CrossRefPubMed

37.

Brown E, Cuthbertson DJ, Wilding JP (2018) Newer GLP-1 receptor agonists and obesity-diabetes. Peptides 100:61–67. https://doi.org/10.1016/j.peptides.2017.12.009CrossRefPubMed

38.

Hsu TM, Noble EE, Liu CM, Cortella AM, Konanur VR, Suarez AN, Reiner DJ, Hahn JD, Hayes MR, Kanoski SE (2017) A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling. Mol Psychiatry 23:1555–1565. https://doi.org/10.1038/mp.2017.91CrossRefPubMedPubMedCentral

39.

Moser MB, Moser EI (1998) Functional differentiation in the hippocampus. Hippocampus 8(6):608–619. https://doi.org/10.1002/(SICI)1098-1063(1998)8:6<608::AID-HIPO3>3.0.CO;2-7CrossRefPubMed

40.

Substance Abuse and Mental Health Services (2013) Results from the 2012 National Survey on Drug Use and Health: mental health findings. NSDUH Series H-47, HHS Publication No. (SMA) 13–4805. Rockville, MD

Titel: GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner
verfasst von: Taylor S. Trammell
Natalie L. Henderson
Haley S. Madkour
Gregg D. Stanwood
Devon L. Graham
Publikationsdatum: 22.11.2020
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 7/2021
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-020-04910-8

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GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner

Abstract

Rationale

Objectives

Methods

Results

Conclusions

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Springer Medizin

Abstract

Rationale

Objectives

Methods

Results

Conclusions

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