Skip to main content

Advertisement

SpringerLink
Log in

A Maternal High-Fat Diet Causes Anxiety-Related Behaviors by Altering Neuropeptide Y1 Receptor and Hippocampal Volumes in Rat Offspring: the Potential Effect of N-Acetylcysteine

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The children of obese mothers are known to have a high risk of obesity and metabolic disease and are prone to developing cognitive deficits, although the underlying mechanism is not yet fully understood. This study investigated the relationship between neuropeptide Y1 receptor (NPY1R) and anxiety-like behaviors in the hippocampi of male rat offspring exposed to maternal obesity and the potential neuroprotective effects of N-acetylcysteine (NAC). A maternal obesity model was created using a high-fat (60% k/cal) diet. NAC (150 mg/kg) was administered by intragastric gavage for 25 days in both the NAC and obesity + NAC (ObNAC) groups. All male rat offspring were subjected to behavioral testing on postnatal day 28, the end of the experiment. Stereological analysis was performed on hippocampal sections, while NPY1R expression was determined using immunohistochemical methods. Stereological data indicated significant decreases in the total volume of the hippocampus and CA1 and dentate gyrus (DG) regions in the obese (Ob) group (p < 0.01). Decreased NPY1R expression was observed in the Ob group hippocampus (p < 0.01). At behavioral assessments, the Ob group rats exhibited increased anxiety and less social interaction, although the ObNAC group rats exhibited stronger responses than the Ob group (p < 0.01). The study results show that NAC attenuated anxiety-like behaviors and NPY1R expression and also protected hippocampal volume against maternal obesity. The findings indicate that a decrease in NPY1R-positive neurons in the hippocampus of male rats due to maternal conditions may be associated with increased levels of anxiety and a lower hippocampal volume. Additionally, although there is no direct evidence, maintenance of NPY1R expression by NAC may be critical for regulating maternal obesity-induced anxiety-related behaviors and hippocampal structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Data are available on request from the authors. The data that support the findings of this study are available from the corresponding author, upon request.

References

  1. van der Burg JW, Sen S, Chomitz VR, Seidell JC, Leviton A, Dammann O (2015) The role of systemic inflammation linking maternal BMI to neurodevelopment in children. Pediatr Res 79(1):3–12. https://doi.org/10.1038/pr.2015.179

    Article  CAS  Google Scholar 

  2. Tozuka Y, Wada E, Wada K (2009) Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring. FASEB J 23(6):1920–1934. https://doi.org/10.1096/fj.08-124784

    Article  CAS  Google Scholar 

  3. Isaacs E, Oates J, ILSI Europe a.i.s.b.l (2008) Nutrition and cognition: assessing cognitive abilities in children and young people. Eur J Nutr 47(Suppl 3):4–24. https://doi.org/10.1007/s00394-008-3002-y

    Article  Google Scholar 

  4. Cordner ZA, Tamashiro KL (2015) Effects of high-fat diet exposure on learning & memory. Physiol Behav 152(Pt B):363–371. https://doi.org/10.1016/j.physbeh.2015.06.008

    Article  CAS  Google Scholar 

  5. Contu L, Hawkes CA (2017) A review of the impact of maternal obesity on the cognitive function and mental health of the offspring. Int J Mol Sci 18(5):1093. https://doi.org/10.3390/ijms18051093

    Article  CAS  Google Scholar 

  6. Bilder DA, Bakian AV, Viskochil J, Clark EA, Botts EL, Smith KR, Pimentel R, McMahon WM, Coon H (2013) Maternal prenatal weight gain and autism spectrum disorders. Pediatrics 132(5):e1276-1283. https://doi.org/10.1542/peds.2013-1188

    Article  Google Scholar 

  7. Dodds L, Fell DB, Shea S, Armson BA, Allen AC, Bryson S (2011) The role of prenatal, obstetric and neonatal factors in the development of autism. J Autism Dev Disord 41(7):891–902. https://doi.org/10.1007/s10803-010-1114-8

    Article  Google Scholar 

  8. Page KA, Luo S, Wang X, Alves J, Martinez MP, Xiang A (2018) Maternal obesity is associated with reduced hippocampal volume in children. Diabetes 67:227-OR

    Article  Google Scholar 

  9. Niculescu MD, Lupu DS (2009) High fat diet-induced maternal obesity alters fetal hippocampal development. Int J Dev Neurosci 27(7):627–633. https://doi.org/10.1016/j.ijdevneu.2009.08.005

    Article  CAS  Google Scholar 

  10. Ledreux A, Wang X, Schultzberg M, Granholm AC, Freeman LR (2016) Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats. Behav Brain Res 312:294–304. https://doi.org/10.1016/j.bbr.2016.06.012

    Article  CAS  Google Scholar 

  11. Winocur G, Greenwood CE (1999) The effects of high fat diets and environmental influences on cognitive performance in rats. Behav Brain Res 101(2):153–161. https://doi.org/10.1016/s0166-4328(98)00147-8

    Article  CAS  Google Scholar 

  12. Hargrave SL, Davidson TL, Lee TJ, Kinzig KP (2015) Brain and behavioral perturbations in rats following Western diet access. Appetite 93:35–43. https://doi.org/10.1016/j.appet.2015.03.037

    Article  Google Scholar 

  13. Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A (2012) Neuroimaging and obesity: current knowledge and future directions. Obes Rev 13(1):43–56. https://doi.org/10.1111/j.1467-789X.2011.00927.x

    Article  CAS  Google Scholar 

  14. Gotzsche CR, Woldbye DP (2016) The role of NPY in learning and memory. Neuropeptides 55:79–89. https://doi.org/10.1016/j.npep.2015.09.010

    Article  CAS  Google Scholar 

  15. Paterlini S, Panelli R, Gioiosa L, Parmigiani S, Franceschini P, Bertocchi I, Oberto A, Bartolomucci A, Eva C, Palanza P (2021) Conditional inactivation of limbic neuropeptide Y-1 receptors increases vulnerability to diet-induced obesity in male mice. Int J Mol Sci 22(16):8745. https://doi.org/10.3390/ijms22168745

  16. Eva C, Serra M, Mele P, Panzica G, Oberto A (2006) Physiology and gene regulation of the brain NPY Y1 receptor. Front Neuroendocrinol 27(3):308–339. https://doi.org/10.1016/j.yfrne.2006.07.002

    Article  CAS  Google Scholar 

  17. Eva C, Oberto A, Longo A, Palanza P, Bertocchi I (2020) Sex differences in behavioral and metabolic effects of gene inactivation: the neuropeptide Y and Y receptors in the brain. Neurosci Biobehav Rev 119:333–347. https://doi.org/10.1016/j.neubiorev.2020.09.020

    Article  CAS  Google Scholar 

  18. Zammaretti F, Panzica G, Eva C (2007) Sex-dependent regulation of hypothalamic neuropeptide Y-Y1 receptor gene expression in moderate/high fat, high-energy diet-fed mice. J Physiol 583(Pt 2):445–454. https://doi.org/10.1113/jphysiol.2007.133470

    Article  CAS  Google Scholar 

  19. Matera MG, Calzetta L, Cazzola M (2016) Oxidation pathway and exacerbations in COPD: the role of NAC. Expert Rev Respir Med 10(1):89–97. https://doi.org/10.1586/17476348.2016.1121105

    Article  CAS  Google Scholar 

  20. Parsanathan R, Jain SK (2019) Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci Rep 9(1):14784. https://doi.org/10.1038/s41598-019-51377-5

    Article  CAS  Google Scholar 

  21. Sedlak TW, Paul BD, Parker GM, Hester LD, Snowman AM, Taniguchi Y, Kamiya A, Snyder SH, Sawa A (2019) The glutathione cycle shapes synaptic glutamate activity. Proc Natl Acad Sci U S A 116(7):2701–2706. https://doi.org/10.1073/pnas.1817885116

    Article  CAS  Google Scholar 

  22. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA (2007) N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 7(4):355–359. https://doi.org/10.1016/j.coph.2007.04.005

    Article  CAS  Google Scholar 

  23. Souza GA, Ebaid GX, Seiva FR, Rocha KH, Galhardi CM, Mani F, Novelli EL (2011) N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects. Evid Based Complement Alternat Med 2011:643269. https://doi.org/10.1093/ecam/nen070

    Article  Google Scholar 

  24. Menting MD, van de Beek C, Mintjens S, Wever KE, Korosi A, Ozanne SE, Limpens J, Roseboom TJ, Hooijmans C, Painter RC (2019) The link between maternal obesity and offspring neurobehavior: a systematic review of animal experiments. Neurosci Biobehav Rev 98:107–121. https://doi.org/10.1016/j.neubiorev.2018.12.023

    Article  Google Scholar 

  25. Hanson MA, Gluckman PD (2014) Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev 94(4):1027–1076. https://doi.org/10.1152/physrev.00029.2013

    Article  CAS  Google Scholar 

  26. Hart AM, Terenghi G, Kellerth JO, Wiberg M (2004) Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury. Neuroscience 125(1):91–101. https://doi.org/10.1016/j.neuroscience.2003.12.040

    Article  CAS  Google Scholar 

  27. Altunkaynak ME, Ozbek E, Altunkaynak BZ, Can I, Unal D, Unal B (2008) The effects of high-fat diet on the renal structure and morphometric parametric of kidneys in rats. J Anat 212(6):845–852. https://doi.org/10.1111/j.1469-7580.2008.00902.x

    Article  Google Scholar 

  28. Tumentemur G, Altunkaynak BZ, Kaplan S (2020) Is melatonin, leptin or their combination more effective on oxidative stress and folliculogenesis in the obese rats? J Obstet Gynaecol 40(1):116–127. https://doi.org/10.1080/01443615.2019.1657816

    Article  CAS  Google Scholar 

  29. Kim KC, Kim P, Go HS, Choi CS, Yang SI, Cheong JH, Shin CY, Ko KH (2011) The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats. Toxicol Lett 201(2):137–142. https://doi.org/10.1016/j.toxlet.2010.12.018

    Article  CAS  Google Scholar 

  30. Kumar H, Sharma BM, Sharma B (2015) Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder. Neurochem Int 91:34–45. https://doi.org/10.1016/j.neuint.2015.10.007

    Article  CAS  Google Scholar 

  31. Yurt KK, Kaplan S, Kivrak EG (2018) The neuroprotective effect of melatonin on the hippocampus exposed to diclofenac sodium during the prenatal period. J Chem Neuroanat 87:37–48. https://doi.org/10.1016/j.jchemneu.2017.05.006

    Article  CAS  Google Scholar 

  32. Gundersen HJ (1986) Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R Thompson. J Microsc 143(1):3–45

    Article  CAS  Google Scholar 

  33. Gundersen HJ, Jensen EB (1987) The efficiency of systematic sampling in stereology and its prediction. J Microsc 147(Pt 3):229–263. https://doi.org/10.1111/j.1365-2818.1987.tb02837.x

    Article  CAS  Google Scholar 

  34. Tuncdemir M, Ozturk M (2011) The effects of angiotensin-II receptor blockers on podocyte damage and glomerular apoptosis in a rat model of experimental streptozotocin-induced diabetic nephropathy. Acta Histochem 113(8):826–832. https://doi.org/10.1016/j.acthis.2010.12.003

    Article  CAS  Google Scholar 

  35. Bilbo SD, Tsang V (2010) Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J 24(6):2104–2115. https://doi.org/10.1096/fj.09-144014

    Article  CAS  Google Scholar 

  36. Peleg-Raibstein D, Luca E, Wolfrum C (2012) Maternal high-fat diet in mice programs emotional behavior in adulthood. Behav Brain Res 233(2):398–404. https://doi.org/10.1016/j.bbr.2012.05.027

    Article  CAS  Google Scholar 

  37. Wright T, Langley-Evans SC, Voigt JP (2011) The impact of maternal cafeteria diet on anxiety-related behaviour and exploration in the offspring. Physiol Behav 103(2):164–172. https://doi.org/10.1016/j.physbeh.2011.01.008

    Article  CAS  Google Scholar 

  38. Balsevich G, Baumann V, Uribe A, Chen A, Schmidt MV (2016) Prenatal exposure to maternal obesity alters anxiety and stress coping behaviors in aged mice. Neuroendocrinology 103(3–4):354–368. https://doi.org/10.1159/000439087

    Article  CAS  Google Scholar 

  39. Langley-Evans SC (2009) Nutritional programming of disease: unravelling the mechanism. J Anat 215(1):36–51. https://doi.org/10.1111/j.1469-7580.2008.00977.x

    Article  Google Scholar 

  40. Tajaddini A, Kendig MD, Prates KV, Westbrook RF, Morris MJ (2022) Male rat offspring are more impacted by maternal obesity induced by cafeteria diet than females-additive effect of postweaning diet. Int J Mol Sci 23(3):1442. https://doi.org/10.3390/ijms23031442

    Article  CAS  Google Scholar 

  41. Kang SS, Kurti A, Fair DA, Fryer JD (2014) Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J Neuroinflammation 11:156. https://doi.org/10.1186/s12974-014-0156-9

    Article  CAS  Google Scholar 

  42. Hayashi R, Kasahara Y, Hidema S, Fukumitsu S, Nakagawa K, Nishimori K (2020) Oxytocin ameliorates impaired behaviors of high fat diet-induced obese mice. Front Endocrinol (Lausanne) 11:379. https://doi.org/10.3389/fendo.2020.00379

    Article  Google Scholar 

  43. Hasebe K, Kendig MD, Morris MJ (2021) Mechanisms underlying the cognitive and behavioural effects of maternal obesity. Nutrients 13(1):240. https://doi.org/10.3390/nu13010240

    Article  CAS  Google Scholar 

  44. Abuaish S, Spinieli RL, McGowan PO (2018) Perinatal high fat diet induces early activation of endocrine stress responsivity and anxiety-like behavior in neonates. Psychoneuroendocrinology 98:11–21. https://doi.org/10.1016/j.psyneuen.2018.08.003

    Article  CAS  Google Scholar 

  45. Sasaki A, de Vega W, Sivanathan S, St-Cyr S, McGowan PO (2014) Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring. Neuroscience 272:92–101. https://doi.org/10.1016/j.neuroscience.2014.04.012

    Article  CAS  Google Scholar 

  46. Sasaki A, de Vega WC, St-Cyr S, Pan P, McGowan PO (2013) Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood. Neuroscience 240:1–12. https://doi.org/10.1016/j.neuroscience.2013.02.044

    Article  CAS  Google Scholar 

  47. Winther G, Elfving B, Muller HK, Lund S, Wegener G (2018) Maternal high-fat diet programs offspring emotional behavior in adulthood. Neuroscience 388:87–101. https://doi.org/10.1016/j.neuroscience.2018.07.014

    Article  CAS  Google Scholar 

  48. Bertocchi I, Oberto A, Longo A, Mele P, Sabetta M, Bartolomucci A, Palanza P, Sprengel R, Eva C (2011) Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care. Proc Natl Acad Sci U S A 108(48):19395–19400. https://doi.org/10.1073/pnas.1109468108

    Article  Google Scholar 

  49. Heilig M (2004) The NPY system in stress, anxiety and depression. Neuropeptides 38(4):213–224. https://doi.org/10.1016/j.npep.2004.05.002

    Article  CAS  Google Scholar 

  50. Karl T, Burne TH, Herzog H (2006) Effect of Y1 receptor deficiency on motor activity, exploration, and anxiety. Behav Brain Res 167(1):87–93. https://doi.org/10.1016/j.bbr.2005.08.019

    Article  CAS  Google Scholar 

  51. Goyal SN, Upadhya MA, Kokare DM, Bhisikar SM, Subhedar NK (2009) Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: involvement of NPY Y1 receptors. Brain Res 1266:45–53. https://doi.org/10.1016/j.brainres.2009.02.033

    Article  CAS  Google Scholar 

  52. Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev 17(1):51–68. https://doi.org/10.1016/s0149-7634(05)80230-1

    Article  CAS  Google Scholar 

  53. Caberlotto L, Fuxe K, Overstreet DH, Gerrard P, Hurd YL (1998) Alterations in neuropeptide Y and Y1 receptor mRNA expression in brains from an animal model of depression: region specific adaptation after fluoxetine treatment. Brain Res Mol Brain Res 59(1):58–65. https://doi.org/10.1016/s0169-328x(98)00137-5

    Article  CAS  Google Scholar 

  54. Reuss S, Hurlbut EC, Speh JC, Moore RY (1990) Neuropeptide Y localization in telencephalic and diencephalic structures of the ground squirrel brain. Am J Anat 188(2):163–174. https://doi.org/10.1002/aja.1001880206

    Article  CAS  Google Scholar 

  55. Li Q, Bartley AF, Dobrunz LE (2017) Endogenously released neuropeptide Y suppresses hippocampal short-term facilitation and is impaired by stress-induced anxiety. J Neurosci 37(1):23–37. https://doi.org/10.1523/JNEUROSCI.2599-16.2016

    Article  Google Scholar 

  56. Flood JF, Hernandez EN, Morley JE (1987) Modulation of memory processing by neuropeptide Y. Brain Res 421(1–2):280–290. https://doi.org/10.1016/0006-8993(87)91297-2

    Article  CAS  Google Scholar 

  57. Holmes PV, Davis RC, Masini CV, Primeaux SD (1998) Effects of olfactory bulbectomy on neuropeptide gene expression in the rat olfactory/limbic system. Neuroscience 86(2):587–596. https://doi.org/10.1016/s0306-4522(98)00029-3

    Article  CAS  Google Scholar 

  58. Overstreet DH, Rezvani AH, Janowsky DS (1992) Genetic animal models of depression and ethanol preference provide support for cholinergic and serotonergic involvement in depression and alcoholism. Biol Psychiatry 31(9):919–936. https://doi.org/10.1016/0006-3223(92)90118-j

    Article  CAS  Google Scholar 

  59. Thorsell A, Michalkiewicz M, Dumont Y, Quirion R, Caberlotto L, Rimondini R, Mathe AA, Heilig M (2000) Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression. Proc Natl Acad Sci U S A 97(23):12852–12857. https://doi.org/10.1073/pnas.220232997

    Article  CAS  Google Scholar 

  60. Dimitrov EL, DeJoseph MR, Brownfield MS, Urban JH (2007) Involvement of neuropeptide Y Y1 receptors in the regulation of neuroendocrine corticotropin-releasing hormone neuronal activity. Endocrinology 148(8):3666–3673. https://doi.org/10.1210/en.2006-1730

    Article  CAS  Google Scholar 

  61. Baudrand R, Vaidya A (2015) Cortisol dysregulation in obesity-related metabolic disorders. Curr Opin Endocrinol Diabetes Obes 22(3):143–149. https://doi.org/10.1097/MED.0000000000000152

    Article  CAS  Google Scholar 

  62. Incollingo Rodriguez AC, Epel ES, White ML, Standen EC, Seckl JR, Tomiyama AJ (2015) Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: a systematic review. Psychoneuroendocrinology 62:301–318. https://doi.org/10.1016/j.psyneuen.2015.08.014

    Article  CAS  Google Scholar 

  63. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB (1995) MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 152(7):973–981. https://doi.org/10.1176/ajp.152.7.973

    Article  CAS  Google Scholar 

  64. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157(1):115–118. https://doi.org/10.1176/ajp.157.1.115

    Article  CAS  Google Scholar 

  65. Villarreal G, Hamilton DA, Petropoulos H, Driscoll I, Rowland LM, Griego JA, Kodituwakku PW, Hart BL, Escalona R, Brooks WM (2002) Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder. Biol Psychiatry 52(2):119–125. https://doi.org/10.1016/s0006-3223(02)01359-8

    Article  Google Scholar 

  66. Yau SY, Lee TH, Li A, Xu A, So KF (2018) Adiponectin mediates running-restored hippocampal neurogenesis in streptozotocin-induced type 1 diabetes in mice. Front Neurosci 12:679. https://doi.org/10.3389/fnins.2018.00679

    Article  Google Scholar 

  67. Hwang IK, Kim IY, Kim DW, Yoo KY, Kim YN, Yi SS, Won MH, Lee IS, Yoon YS, Seong JK (2008) Strain-specific differences in cell proliferation and differentiation in the dentate gyrus of C57BL/6N and C3H/HeN mice fed a high fat diet. Brain Res 1241:1–6. https://doi.org/10.1016/j.brainres.2008.08.024

    Article  CAS  Google Scholar 

  68. Beauquis J, Saravia F, Coulaud J, Roig P, Dardenne M, Homo-Delarche F, De Nicola A (2008) Prominently decreased hippocampal neurogenesis in a spontaneous model of type 1 diabetes, the nonobese diabetic mouse. Exp Neurol 210(2):359–367. https://doi.org/10.1016/j.expneurol.2007.11.009

    Article  CAS  Google Scholar 

  69. Lindqvist A, Mohapel P, Bouter B, Frielingsdorf H, Pizzo D, Brundin P, Erlanson-Albertsson C (2006) High-fat diet impairs hippocampal neurogenesis in male rats. Eur J Neurol 13(12):1385–1388. https://doi.org/10.1111/j.1468-1331.2006.01500.x

    Article  CAS  Google Scholar 

  70. Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Laye S, Ferreira G (2012) Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice. Hippocampus 22(11):2095–2100. https://doi.org/10.1002/hipo.22032

    Article  CAS  Google Scholar 

  71. Ho N, Sommers MS, Lucki I (2013) Effects of diabetes on hippocampal neurogenesis: links to cognition and depression. Neurosci Biobehav Rev 37(8):1346–1362. https://doi.org/10.1016/j.neubiorev.2013.03.010

    Article  CAS  Google Scholar 

  72. Wolak ML, DeJoseph MR, Cator AD, Mokashi AS, Brownfield MS, Urban JH (2003) Comparative distribution of neuropeptide Y Y1 and Y5 receptors in the rat brain by using immunohistochemistry. J Comp Neurol 464(3):285–311. https://doi.org/10.1002/cne.10823

    Article  CAS  Google Scholar 

  73. Pedrazzini T, Seydoux J, Kunstner P, Aubert JF, Grouzmann E, Beermann F, Brunner HR (1998) Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor. Nat Med 4(6):722–726. https://doi.org/10.1038/nm0698-722

    Article  CAS  Google Scholar 

  74. Mahmoodzadeh Y, Mahmoudi J, Gorgani-Firuzjaee S, Mohtavinejad N, Namvaran A (2021) Effects of N-acetylcysteine on noise exposure-induced oxidative stress and depressive- and anxiety-like behaviors in adult male mice. Basic Clin Neurosci 12(4):499–510. https://doi.org/10.32598/bcn.2021.2026.1

    Article  CAS  Google Scholar 

  75. Mocelin R, Herrmann AP, Marcon M, Rambo CL, Rohden A, Bevilaqua F, de Abreu MS, Zanatta L, Elisabetsky E, Barcellos LJ, Lara DR, Piato AL (2015) N-Acetylcysteine prevents stress-induced anxiety behavior in zebrafish. Pharmacol Biochem Behav 139(Pt B):121–126

    Article  CAS  Google Scholar 

  76. Santos P, Herrmann AP, Benvenutti R, Noetzold G, Giongo F, Gama CS, Piato AL, Elisabetsky E (2017) Anxiolytic properties of N-acetylcysteine in mice. Behav Brain Res 317:461–469. https://doi.org/10.1016/j.bbr.2016.10.010

    Article  CAS  Google Scholar 

  77. Vukovic R, Kumburovic I, JoksimovicJovic J, Jovicic N, KatanicStankovic JS, Mihailovic V, Djuric M, Velickovic S, Arnaut A, Selakovic D, Rosic G (2019) N-Acetylcysteine protects against the anxiogenic response to cisplatin in rats. Biomolecules 9(12):892. https://doi.org/10.3390/biom9120892

    Article  CAS  Google Scholar 

  78. Kitamura Y, Ushio S, Sumiyoshi Y, Wada Y, Miyazaki I, Asanuma M, Sendo T (2021) N-Acetylcysteine attenuates the anxiety-like behavior and spatial cognition impairment induced by doxorubicin and cyclophosphamide combination treatment in rats. Pharmacology 106(5–6):286–293. https://doi.org/10.1159/000512117

    Article  CAS  Google Scholar 

  79. Martins J, Elvas F, Brudzewsky D, Martins T, Kolomiets B, Tralhao P, Gotzsche CR, Cavadas C, Castelo-Branco M, Woldbye DP, Picaud S, Santiago AR, Ambrosio AF (2015) Activation of neuropeptide Y receptors modulates retinal ganglion cell physiology and exerts neuroprotective actions in vitro. ASN Neuro 7(4):1759091415598292. https://doi.org/10.1177/1759091415598292

    Article  CAS  Google Scholar 

  80. Hansel DE, Eipper BA, Ronnett GV (2001) Neuropeptide Y functions as a neuroproliferative factor. Nature 410(6831):940–944. https://doi.org/10.1038/35073601

    Article  CAS  Google Scholar 

  81. Howell OW, Scharfman HE, Herzog H, Sundstrom LE, Beck-Sickinger A, Gray WP (2003) Neuropeptide Y is neuroproliferative for post-natal hippocampal precursor cells. J Neurochem 86(3):646–659. https://doi.org/10.1046/j.1471-4159.2003.01895.x

    Article  CAS  Google Scholar 

  82. Milenkovic I, Weick M, Wiedemann P, Reichenbach A, Bringmann A (2004) Neuropeptide Y-evoked proliferation of retinal glial (Muller) cells. Graefes Arch Clin Exp Ophthalmol 242(11):944–950. https://doi.org/10.1007/s00417-004-0954-3

    Article  CAS  Google Scholar 

  83. Movafagh S, Hobson JP, Spiegel S, Kleinman HK, Zukowska Z (2006) Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors. FASEB J 20(11):1924–1926. https://doi.org/10.1096/fj.05-4770fje

    Article  CAS  Google Scholar 

  84. Agasse F, Bernardino L, Kristiansen H, Christiansen SH, Ferreira R, Silva B, Grade S, Woldbye DP, Malva JO (2008) Neuropeptide Y promotes neurogenesis in murine subventricular zone. Stem Cells 26(6):1636–1645. https://doi.org/10.1634/stemcells.2008-0056

    Article  CAS  Google Scholar 

  85. Calzadilla P, Gomez-Serrano M, Garcia-Santos E, Schiappacasse A, Abalde Y, Calvo JC, Peral B, Guerra LN (2013) N-Acetylcysteine affects obesity-related protein expression in 3T3-L1 adipocytes. Redox Rep 18(6):210–218. https://doi.org/10.1179/1351000213Y.0000000066

    Article  CAS  Google Scholar 

  86. Dwir D, Cabungcal JH, Xin L, Giangreco B, Parietti E, Cleusix M, Jenni R, Klauser P, Conus P, Cuenod M, Steullet P, Do KQ (2021) Timely N-acetyl-cysteine and environmental enrichment rescue oxidative stress-induced parvalbumin interneuron impairments via MMP9/RAGE pathway: a translational approach for early intervention in psychosis. Schizophr Bull 47(6):1782–1794. https://doi.org/10.1093/schbul/sbab066

    Article  Google Scholar 

  87. Alba M, Garcia-Serrano JPPV, Veronika Fleischhart, João MN (2022) Taurine or N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice. bioRxiv 17(Suppl.4):e053779. https://doi.org/10.1101/2022.02.02.478774

Download references

Funding

This study was supported by a grant from the Scientific Research Foundation of Kastamonu University (Kıymet Kübra Tüfekci; KUBAP01/2021–03).

Author information

Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Kastamonu University, Kastamonu, Turkey

    Kıymet Kübra Tüfekci

  2. Department of Histology and Embryology, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey

    Elfide Gizem Bakirhan

  3. Department of Pathology, Faculty of Veterinary Medicine, Kastamonu University, Kastamonu, Turkey

    Funda Terzi

Authors
  1. Kıymet Kübra Tüfekci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elfide Gizem Bakirhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Funda Terzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to designing, writing, and editing the manuscript. Kıymet Kübra Tüfekci and Elfide Gizem Bakırhan performed the experiments and behavior tests analyzed as well as interpreted the data and contributed to writing the paper. Funda Terzi wrote and revised the paper. Kıymet Kübra Tüfekci contributed to experimental design, supervised the data writing, and revised the whole manuscript.

Corresponding author

Correspondence to Kıymet Kübra Tüfekci.

Ethics declarations

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Adıyaman University (Dated 25.02.2021/No. 2021/001).

Consent to Participate

Not applicable.

Consent for Publication

All authors read and approved the final manuscript.

Competing Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 83 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tüfekci, K.K., Bakirhan, E.G. & Terzi, F. A Maternal High-Fat Diet Causes Anxiety-Related Behaviors by Altering Neuropeptide Y1 Receptor and Hippocampal Volumes in Rat Offspring: the Potential Effect of N-Acetylcysteine. Mol Neurobiol 60, 1499–1514 (2023). https://doi.org/10.1007/s12035-022-03158-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-022-03158-x

Keywords

Search

Navigation