Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Intranasal insulin ameliorates prenatal LPS-induced learning and memory impairments in adolescent male rats: A behavioral, electrophysiological, and molecular study
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 21 February 2026

Intranasal insulin ameliorates prenatal LPS-induced learning and memory impairments in adolescent male rats: A behavioral, electrophysiological, and molecular study

  • Hadis Kariminejad-Farsangi1,
  • Haniyeh Kariminejad-Farsangi1,
  • Mohammad Amin Rajizadeh2,
  • Mahdiyeh Abbaspoor1,
  • Lily Mohammadipoor-Ghasemabad1,
  • Sara Joushi1 an1 &
  • …
  • Vahid Sheibani1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Neuroscience
  • Physiology

Abstract

Prenatal stress, including maternal immune activation (MIA), affects cognitive performance in the offspring. Since insulin could improve cognitive function in several aspects, we hypothesized that intranasal insulin would attenuate MIA-induced learning and memory deficits. In the present study, the pregnant Wistar rats received lipopolysaccharide (LPS, 250 µg/kg) intraperitoneally on gestational day 15. Intranasal insulin (2 IU, 7 days) was administered to male pups from PND 34–47. During late adolescence, the Morris Water Maze and in vivo electrophysiological recording were performed in male rats to assess spatial learning and memory and long-term potentiation (LTP), respectively. Also, the hippocampal expression of BDNF and PSD-95 was evaluated using real-time PCR. Our results demonstrated that MIA impaired spatial learning and memory in the male pups. Hippocampal synaptic plasticity was also impaired in the adolescent male rats. However, intranasal administration of insulin could overcome MIA-induced impairments and improve learning, memory, and synaptic plasticity in the male pups. Although BDNF and PSD-95 levels were not altered in the hippocampus of MIA pups, intranasal insulin increased PSD-95 expression. Taken together, these findings suggest that intranasal insulin promotes cognitive performance in MIA-exposed pups during adolescence; however, the underlying molecular mechanisms remain to be elucidated.

Similar content being viewed by others

Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Article Open access 29 July 2021

Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease

Article Open access 10 July 2024

Cognitive impairment in obese rat model: role of glial cells

Article 17 June 2021

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

References

  1. O’Connor, T. G. & Ciesla, A. A. Maternal immune activation hypotheses for human neurodevelopment: some outstanding questions. Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 7 (5), 471–479 (2022).

    Google Scholar 

  2. Csatlosova, K. et al. Maternal immune activation in rats attenuates the excitability of monoamine-secreting neurons in adult offspring in a sex-specific way. Eur. Neuropsychopharmacol. 43, 82–91 (2021).

    Google Scholar 

  3. Al-Haddad, B. J. S. et al. Long-term risk of neuropsychiatric disease after exposure to infection in utero. JAMA Psychiatry. 76 (6), 594–602 (2019).

    Google Scholar 

  4. Atladóttir, H. O. et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J. Autism Dev. Disord. 40 (12), 1423–1430 (2010).

    Google Scholar 

  5. Lee, B. K. et al. Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain Behav. Immun. 44, 100–105 (2015).

    Google Scholar 

  6. Lydholm, C. N. et al. Parental infections Before, During, and after pregnancy as risk factors for mental disorders in childhood and adolescence: A nationwide Danish study. Biol. Psychiatry. 85 (4), 317–325 (2019).

    Google Scholar 

  7. Vlasova, R. M. et al. Maternal immune activation during pregnancy alters postnatal brain growth and cognitive development in nonhuman primate offspring. J. Neurosci. 41 (48), 9971–9987 (2021).

    Google Scholar 

  8. Couch, A. C. M. et al. Maternal immune activation primes deficiencies in adult hippocampal neurogenesis. Brain Behav. Immun. 97, 410–422 (2021).

    Google Scholar 

  9. Knuesel, I. et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat. Rev. Neurol. 10 (11), 643–660 (2014).

    Google Scholar 

  10. Smolders, S., Notter, T., Smolders, S. M. T., Rigo, J-M. & Brône, B. Controversies and prospects about microglia in maternal immune activation models for neurodevelopmental disorders. Brain Behav. Immun. 73, 51–65 (2018).

    Google Scholar 

  11. Matteoli, M., Pozzi, D., Fossati, M. & Menna, E. Immune synaptopathies: how maternal immune activation impacts synaptic function during development. EMBO J. 42 (13), e113796 (2023).

    Google Scholar 

  12. Murray, K. N. et al. Evolution of a maternal immune activation (mIA) model in rats: early developmental effects. Brain Behav. Immun. 75, 48–59 (2019).

    Google Scholar 

  13. Oskvig, D. B., Elkahloun, A. G., Johnson, K. R., Phillips, T. M. & Herkenham, M. Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response. Brain Behav. Immun. 26 (4), 623–634 (2012).

    Google Scholar 

  14. Quagliato, L. A., de Matos, U. & Nardi, A. E. Maternal immune activation generates anxiety in offspring: A translational meta-analysis. Transl Psychiatry. 11 (1), 1–6 (2021).

    Google Scholar 

  15. Dutra, M. L. et al. Maternal immune activation induces autism-like behavior and reduces brain-derived neurotrophic factor levels in the hippocampus and offspring cortex of C57BL/6 mice. Neurosci Lett [Internet]. ;793:136974. (2023). Available from: https://www.sciencedirect.com/science/article/pii/S0304394022005353

  16. Perez-Palomar, B., Erdozain, A. M., Erkizia-Santamaría, I., Ortega, J. E. & Meana, J. J. Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring. J Neuroimmune Pharmacol [Internet]. ;18(3):348–65. (2023). Available from: https://doi.org/10.1007/s11481-023-10070-1

  17. Zhang, Y-M. et al. Resveratrol ameliorates maternal immune activation-associated cognitive impairment in adult male offspring by relieving inflammation and improving synaptic dysfunction. Front. Behav. Neurosci. 17, 1271653 (2023).

    Google Scholar 

  18. Glass, R., Norton, S., Fox, N. & Kusnecov, A. W. Maternal immune activation with Staphylococcal enterotoxin A produces unique behavioral changes in C57BL/6 mouse offspring. Brain Behav. Immun. 75, 12–25 (2019).

    Google Scholar 

  19. Khan, D. et al. Long-term effects of maternal immune activation on depression-like behavior in the mouse. Transl Psychiatry. 4 (2), e363 (2014).

    Google Scholar 

  20. Sal-Sarria, S., Conejo, N. M. & González-Pardo, H. Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review. Neurosci. Biobehav Rev. 164, 105844 (2024).

    Google Scholar 

  21. Zhao, Q. et al. Maternal immune activation-induced PPARγ-dependent dysfunction of microglia associated with neurogenic impairment and aberrant postnatal behaviors in offspring. Neurobiol. Dis. 125, 1–13 (2019).

    Google Scholar 

  22. Schaafsma, W. et al. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood. Neurobiol. Dis. 106, 291–300 (2017).

    Google Scholar 

  23. Talukdar, P. M. et al. Maternal immune activation causes Schizophrenia-like behaviors in the offspring through activation of immune-Inflammatory, oxidative and apoptotic Pathways, and Lowered antioxidant defenses and neuroprotection. Mol. Neurobiol. 57 (10), 4345–4361 (2020).

    Google Scholar 

  24. Giovanoli, S., Weber-Stadlbauer, U., Schedlowski, M., Meyer, U. & Engler, H. Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies. Brain Behav. Immun. 55, 25–38 (2016).

    Google Scholar 

  25. Andoh, M. et al. Exercise reverses behavioral and synaptic abnormalities after maternal inflammation. Cell. Rep. 27 (10), 2817–2825e5 (2019).

    Google Scholar 

  26. Yan S, Wang L, Samsom JN, Ujic D, Liu F. PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice, Leading to Decreased Synaptic Spine Density. Int J Mol Sci. 2024 May 17;25(10):5480. doi: 10.3390/ijms25105480. PMID: 38791517; PMCID: PMC11121703.

  27. Bourgeron, T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat. Rev. Neurosci. 16 (9), 551–563 (2015).

    Google Scholar 

  28. Sheibani, V. et al. The effects of neurosteroid allopregnanolone on synaptic dysfunction in the hippocampus in experimental parkinsonism rats: an electrophysiological and molecular study. Neuropeptides 92, 102229 (2022).

    Google Scholar 

  29. Joushi, S., Esmaeilpour, K., Masoumi-Ardakani, Y., Esmaeili-Mahani, S. & Sheibani, V. Effects of short environmental enrichment on early-life adversity induced cognitive alternations in adolescent rats. J. Neurosci. Res. 99 (12), 3373–3391 (2021).

    Google Scholar 

  30. Morris, R. G. M. Long-term potentiation and memory. Philos. Trans. R Soc. Lond. Ser. B Biol. Sci. 358 (1432), 643–647 (2003).

    Google Scholar 

  31. Kowiański, P. et al. BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity. Cell. Mol. Neurobiol. 38 (3), 579–593 (2018).

    Google Scholar 

  32. Colucci-D'Amato L, Speranza L, Volpicelli F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int J Mol Sci. 2020 Oct 21;21(20):7777. doi: 10.3390/ijms21207777. PMID: 33096634; PMCID: PMC7589016.

  33. Levy AM, Gomez-Puertas P, Tümer Z. Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners. Int J Mol Sci. 2022 Apr 15;23(8):4390. doi: 10.3390/ijms23084390. PMID: 35457207; PMCID: PMC9025546.

  34. Coley, A. A. & Gao, W-J. PSD95: A synaptic protein implicated in schizophrenia or autism? Prog Neuropsychopharmacol. Biol. Psychiatry. 82, 187–194 (2018).

    Google Scholar 

  35. Woods, R. M. et al. Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders. Neuronal Signal. 7 (2), NS20220064 (2023).

    Google Scholar 

  36. Craft, S. et al. Safety, Efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and alzheimer disease dementia: A randomized clinical trial. JAMA Neurol. 77 (9), 1099–1109 (2020).

    Google Scholar 

  37. Lv, H. et al. Intranasal insulin administration May be highly effective in improving cognitive function in mice with cognitive dysfunction by reversing brain insulin resistance. Cogn. Neurodyn. 14 (3), 323–338 (2020).

    Google Scholar 

  38. Rajasekar, N., Nath, C., Hanif, K. & Shukla, R. Intranasal insulin administration ameliorates streptozotocin (ICV)-Induced insulin receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and memory impairment in rats. Mol. Neurobiol. 54 (8), 6507–6522 (2017).

    Google Scholar 

  39. Reger, M. A. et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70 (6), 440–448 (2008).

    Google Scholar 

  40. Benedict, C. et al. Intranasal insulin improves memory in humans. Psychoneuroendocrinology 29 (10), 1326–1334 (2004).

    Google Scholar 

  41. Benedict, C., Kern, W., Schultes, B., Born, J. & Hallschmid, M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J. Clin. Endocrinol. Metab. 93 (4), 1339–1344 (2008).

    Google Scholar 

  42. Benedict, C. et al. Intranasal insulin improves memory in humans: superiority of insulin Aspart. Neuropsychopharmacol. Off Publ Am. Coll. Neuropsychopharmacol. 32 (1), 239–243 (2007).

    Google Scholar 

  43. Reger, M. A. et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J. Alzheimers Dis. 13 (3), 323–331 (2008).

    Google Scholar 

  44. Yang, L. et al. Intranasal insulin ameliorates cognitive impairment in a rat model of parkinson’s disease through Akt/GSK3β signaling pathway. Life Sci. 259, 118159 (2020).

    Google Scholar 

  45. Mao, Y-F. et al. Intranasal insulin alleviates cognitive deficits and amyloid pathology in young adult APPswe/PS1dE9 mice. Aging Cell. 15 (5), 893–902 (2016).

    Google Scholar 

  46. Ramos-Rodriguez, J. J. et al. Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring. Mol. Neurodegener. 12 (1), 57 (2017).

    Google Scholar 

  47. Smith, C. J. et al. Intranasal insulin helps overcome brain insulin deficiency and improves survival and post-stroke cognitive impairment in male mice. J. Neurosci. Res. 101 (11), 1757–1769 (2023).

    Google Scholar 

  48. Núñez Estevez, K. J., Rondón-Ortiz, A. N., Nguyen, J. Q. T. & Kentner, A. C. Environmental influences on placental programming and offspring outcomes following maternal immune activation. Brain Behav Immun [Internet]. ;83:44–55. (2020). Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073165171&doi=10.1016%2Fj.bbi.2019.08.192&partnerID=40&md5=5c284b925870a29a2fd9f09208adda22

  49. Kalish, B. T. et al. Maternal immune activation in mice disrupts proteostasis in the fetal brain. Nat. Neurosci. 24 (2), 204–213 (2021).

    Google Scholar 

  50. Wang, Y., Fu, A. K. Y. & Ip, N. Y. Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms. FEBS J. 289 (8), 2202–2218 (2022).

    Google Scholar 

  51. Tolias, K. F., Duman, J. G. & Um, K. Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog Neurobiol. 94 (2), 133–148 (2011).

    Google Scholar 

  52. Hao, L. Y., Hao, X. Q., Li, S. H. & Li, X. H. Prenatal exposure to lipopolysaccharide results in cognitive deficits in age-increasing offspring rats. Neuroscience [Internet]. ;166(3):763–70. (2010). Available from: https://www.sciencedirect.com/science/article/pii/S0306452210000072

  53. Zhang, T., Dolga, A. M., Eisel, U. L. M. & Schmidt, M. Novel crosstalk mechanisms between GluA3 and Epac2 in synaptic plasticity and memory in alzheimer’s disease. Neurobiol. Dis. 191, 106389 (2024).

    Google Scholar 

  54. Cieślik M, Gąssowska-Dobrowolska M, Jęśko H, Czapski GA, Wilkaniec A, Zawadzka A, Dominiak A, Polowy R, Filipkowski RK, Boguszewski PM, Gewartowska M, Frontczak-Baniewicz M, Sun GY, Beversdorf DQ, Adamczyk A. Maternal Immune Activation Induces Neuroinflammation and Cortical Synaptic Deficits in the Adolescent Rat Offspring. Int J Mol Sci. 2020 Jun 8;21(11):4097. doi: 10.3390/ijms21114097. PMID: 32521803; PMCID: PMC7312084.

  55. Vallejo, D., Codocedo, J. F. & Inestrosa, N. C. Posttranslational modifications regulate the postsynaptic localization of PSD-95. Mol. Neurobiol. 54 (3), 1759–1776 (2017).

    Google Scholar 

  56. Forrest, C. M. et al. Prenatal activation of Toll-like receptors-3 by administration of the viral mimetic poly(I:C) changes synaptic proteins, N-methyl-D-aspartate receptors and neurogenesis markers in offspring. Mol. Brain. 5, 22 (2012).

    Google Scholar 

  57. Schirmbeck, G. H. et al. Long-term LPS systemic administration leads to memory impairment and disturbance in astrocytic homeostasis. Neurotoxicology 99, 322–331 (2023).

    Google Scholar 

  58. Das, S., Mishra, K. P., Ganju, L. & Singh, S. B. Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment. J. Neuroimmunol. 313, 161–175 (2017).

    Google Scholar 

  59. Hemmerle, A. M. et al. Modulation of schizophrenia-related genes in the forebrain of adolescent and adult rats exposed to maternal immune activation. Schizophr Res. 168 (1–2), 411–420 (2015).

    Google Scholar 

  60. Han, M., Zhang, J-C., Huang, X-F. & Hashimoto, K. Intake of 7,8-dihydroxyflavone from pregnancy to weaning prevents cognitive deficits in adult offspring after maternal immune activation. Eur. Arch. Psychiatry Clin. Neurosci. 267 (5), 479–483 (2017).

    Google Scholar 

  61. Cieślik, M. et al. The synaptic dysregulation in adolescent rats exposed to maternal immune activation. Front. Mol. Neurosci. 13, 555290 (2020).

    Google Scholar 

  62. de la Monte, S. M. Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the Art. Expert Opin. Drug Deliv. 10 (12), 1699–1709 (2013).

    Google Scholar 

  63. Zhao, F., Siu, J. J., Huang, W., Askwith, C. & Cao, L. Insulin modulates excitatory synaptic transmission and synaptic plasticity in the mouse hippocampus. Neuroscience 411, 237–254 (2019).

    Google Scholar 

  64. Barutçu, Ö. et al. Insulin-induced long-term potentiation in the dentate gyrus of hippocampal formation. Psychoneuroendocrinology 157, 106343 (2023).

    Google Scholar 

  65. van der Heide, L. P., Kamal, A., Artola, A., Gispen, W. H. & Ramakers, G. M. J. Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. J. Neurochem. 94 (4), 1158–1166 (2005).

    Google Scholar 

  66. Chen, Y. et al. Intranasal insulin prevents Anesthesia-Induced cognitive impairment and chronic neurobehavioral changes. Front. Aging Neurosci. 9, 136 (2017).

    Google Scholar 

  67. Maimaiti, S. et al. Intranasal insulin improves Age-Related cognitive deficits and reverses electrophysiological correlates of brain aging. J. Gerontol. Biol. Sci. Med. Sci. 71 (1), 30–39 (2016).

    Google Scholar 

  68. Roque, P. S. et al. Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1. Sci. Rep. 11 (1), 15490 (2021).

    Google Scholar 

  69. Yu, Q. et al. Intranasal insulin increases synaptic protein expression and prevents Anesthesia-Induced cognitive deficits through mTOR-eEF2 pathway. J. Alzheimers Dis. 70 (3), 925–936 (2019).

    Google Scholar 

  70. Rajasekar, N., Nath, C., Hanif, K. & Shukla, R. Intranasal insulin improves cerebral blood flow, Nrf-2 expression and BDNF in STZ (ICV)-induced memory impaired rats. Life Sci. 173, 1–10 (2017).

    Google Scholar 

  71. Simon, K. U. et al. da RP,. Intranasal insulin treatment modulates the neurotropic, inflammatory, and oxidant mechanisms in the cortex and hippocampus in a low-grade inflammation model. Peptides. ;123:170175. (2020).

  72. Ivanov, A. D., Tukhbatova, G. R., Salozhin, S. V. & Markevich, V. A. NGF but not BDNF overexpression protects hippocampal LTP from beta-amyloid-induced impairment. Neuroscience 289, 114–122 (2015).

    Google Scholar 

  73. Cao, H. et al. High frequency repetitive transcranial magnetic stimulation alleviates cognitive deficits in 3xTg-AD mice by modulating the PI3K/Akt/GLT-1 axis. Redox Biol. 54, 102354 (2022).

    Google Scholar 

  74. Lee, C-C., Huang, C-C. & Hsu, K-S. Insulin promotes dendritic spine and synapse formation by the PI3K/Akt/mTOR and Rac1 signaling pathways. Neuropharmacology 61 (4), 867–879 (2011).

    Google Scholar 

  75. Akhtar, A. & Sah, S. P. Insulin signaling pathway and related molecules: role in neurodegeneration and alzheimer’s disease. Neurochem Int. 135, 104707 (2020).

    Google Scholar 

  76. Joushi, S., Esmaeilpour, K., Masoumi-Ardakani, Y., Esmaeili-Mahani, S. & Sheibani, V. Intranasal Oxytocin administration facilitates the induction of long-term potentiation and promotes cognitive performance of maternally separated rats. Psychoneuroendocrinology 123, 105044 (2021).

    Google Scholar 

  77. Marks, D. R., Tucker, K., Cavallin, M. A., Mast, T. G. & Fadool, D. A. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J. Neurosci. Off J. Soc. Neurosci. 29 (20), 6734–6751 (2009).

    Google Scholar 

  78. Rehman, N. U. et al. Effect of 4-Fluoro-N-(4-sulfamoylbenzyl) benzene sulfonamide on cognitive deficits and hippocampal plasticity during nicotine withdrawal in rats. Biomed. Pharmacother. 131, 110783 (2020).

    Google Scholar 

  79. Joushi, S. et al. Maternal separation impairs mother’s cognition 1 month beyond the separation. Int. J. Dev. Neurosci. Off J. Int. Soc. Dev. Neurosci. 81 (7), 605–615 (2021).

    Google Scholar 

  80. Rajizadeh, M. A., Esmaeilpour, K., Haghparast, E., Ebrahimi, M. N. & Sheibani, V. Voluntary exercise modulates learning & memory and synaptic plasticity impairments in sleep deprived female rats. Brain Res. 1729, 146598 (2020).

    Google Scholar 

  81. Khodamoradi, M., Asadi-Shekaari, M., Esmaeili-Mahani, S., Esmaeilpour, K. & Sheibani, V. Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat Kainic acid model of seizure. Eur. J. Pharmacol. 786, 1–9 (2016).

    Google Scholar 

  82. Shahraki, S. et al. Choline chloride modulates learning, memory, and synaptic plasticity impairments in maternally separated adolescent male rats. Int. J. Dev. Neurosci. Off J. Int. Soc. Dev. Neurosci. 82 (1), 19–38 (2022).

    Google Scholar 

  83. Salari, M. et al. Impact of sleep deprivation on the brain’s inflammatory response triggered by lipopolysaccharide and its consequences on Spatial learning and memory and Long-Term potentiation in male rats. Neuroimmunomodulation 31 (1), 12–24 (2024).

    Google Scholar 

  84. Fadaei-Kenarsary, M., Esmaeilpour, K., Shabani, M. & Sheibani, V. Chronic maternal morphine exposure and early-life adversity induce impairment in synaptic plasticity of adolescent male rats. Neurosci. Lett. 812, 137365 (2023).

    Google Scholar 

  85. Mohammadipoor-Ghasemabad, L., Sangtarash, M. H., Sheibani, V., Sasan, H. A. & Esmaeili-Mahani, S. Hippocampal microRNA-191a-5p regulates BDNF expression and shows correlation with cognitive impairment induced by Paradoxical sleep deprivation. Neuroscience 414, 49–59 (2019).

    Google Scholar 

Download references

Acknowledgements

This study was supported by Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Funding

In this project, funding for experiments was provided by Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Author information

Authors and Affiliations

  1. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Hadis Kariminejad-Farsangi, Haniyeh Kariminejad-Farsangi, Mahdiyeh Abbaspoor, Lily Mohammadipoor-Ghasemabad, Sara Joushi & Vahid Sheibani

  2. Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Amin Rajizadeh

Author notes

  1. Sara Joushi is the main corresponding author for this work.

    • Sara Joushi
Authors
  1. Hadis Kariminejad-Farsangi
    View author publications

    Search author on:PubMed Google Scholar

  2. Haniyeh Kariminejad-Farsangi
    View author publications

    Search author on:PubMed Google Scholar

  3. Mohammad Amin Rajizadeh
    View author publications

    Search author on:PubMed Google Scholar

  4. Mahdiyeh Abbaspoor
    View author publications

    Search author on:PubMed Google Scholar

  5. Lily Mohammadipoor-Ghasemabad
    View author publications

    Search author on:PubMed Google Scholar

  6. Sara Joushi
    View author publications

    Search author on:PubMed Google Scholar

  7. Vahid Sheibani
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Hadis.K. and Haniyeh.K. contributed to modeling, performed the behavioral experiments and molecular assessments, analyzed the data and wrote the manuscript. M.R. contributed to electrophysiological experiment. M.A. contributed to modeling and behavioral experiments. L.M. contributed to molecular assessments. S.J. designed and supervised the project and contributed to interpretation of the results, and revised the manuscript. V.Sh. supervised the project.

Corresponding authors

Correspondence to Sara Joushi or Vahid Sheibani.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics declarations

All experiments were done in accordance with the ARRIVE guidelines and National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80 − 23, revised 1996). All experimental procedures were conducted in accordance with institutional and international guidelines for animal care, as approved by the Institutional Animal Research Ethics Committee of Kerman University of Medical Sciences (Ethics code: IR.KMU.AEC.1402.84).

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 Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kariminejad-Farsangi, H., Kariminejad-Farsangi, H., Rajizadeh, M.A. et al. Intranasal insulin ameliorates prenatal LPS-induced learning and memory impairments in adolescent male rats: A behavioral, electrophysiological, and molecular study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40163-9

Download citation

  • Received: 18 July 2025

  • Accepted: 10 February 2026

  • Published: 21 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-40163-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Maternal immune activation (MIA)
  • Intranasal insulin
  • Long term potentiation (LTP)
  • Learning and memory
  • BDNF
  • PSD-95
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing