Journal of Kerman University of Medical Sciences

Crocin Administration from Childhood to Adulthood Increases Hippocampal Neurogenesis and Synaptogenesis in Male Mice

Document Type : Original Article

Authors

Babak Ebrahimi 1
Shayan Vafaei 2
Seyed Hamid Reza Rastegar-Moghaddam 2
Mahmoud Hosseini 3
Fatemeh Tajik Yabr 2
Abbas Mohammadipour 2

1 Department of Anatomy, School of Medicine, Tehran University of medical sciences, Tehran, Iran

2 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

https://doi.org/10.22062/jkmu.2021.91664
Abstract
Background: Adult hippocampal neurogenesis and synaptogenesis play a critical role in learning and memory. Crocin as a carotenoid has many neuroprotective effects but its effect on neurogenesis and synaptogenesis is unknown. In this study, the effects of crocin administration from post-lactation period to adulthood on the mice hippocampal neurogenesis and synaptogenesis were investigated.
Methods: 12 mice offspring were divided into 2 groups of control and crocin. Animals in the crocin group received 30 mg/kg of crocin from postnatal day 30 to 75 through drinking water. At the same time, the control group received drinking water without crocin. At the end of the treatment, animals were sacrificed and their brains were removed. The brains were sectioned and stained by immunohistochemical technique to evaluate the effect of crocin on hippocampal doublecortin (DCX) positive cells and synaptophysin expression.
Results: The results of the immunohistochemistry showed that the mean number of DCX+ cells in the dentate gyrus (DG) of the crocin group was significantly higher than that in the control group. In addition, the synaptophysin expression was higher in the cornu ammonis (CA) of the hippocampus in the crocin group.
Conclusion: According to the results, consumption of crocin from childhood to adulthood may increase hippocampal neurogenesis and synaptogenesis.

Keywords

Crocin
Dentate gyrus
Hippocampus
Neurogenesis
Synaptogenesis
  1. Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 2010; 11(5):339-50.
  2. Lieberwirth C, Pan Y, Liu Y, Zhang Z, Wang Z. Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory. Brain Res 2016; 1644:127-40.
  3. Ebrahimzadeh Bideskan A, Mohammadipour A, Fazel A, Haghir H, Rafatpanah H, Hosseini M, et al. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis. Exp Toxicol Pathol 2017; 69(6):329-37.
  4. Mahar I, MacIsaac A, Kim JJ, Qiang C, Davoli MA, Turecki G, et al. Effects of neuregulin-1 administration on neurogenesis in the adult mouse hippocampus, and characterization of immature neurons along the septotemporal axis. Scientific Reports 2016; 6:30467.
  5. Rastegar-Moghaddam SH, Mohammadipour A, Hosseini M, Bargi R, Ebrahimzadeh-Bideskan, A. Maternal exposure to atrazine induces the hippocampal cell apoptosis in mice offspring and impairs their learning and spatial memory. Toxin Reviews 2019; 38(4):298-306.
  6. Kase Y, Otsu K, Shimazaki T, Okano H. Involvement of p38 in age-related decline in adult neurogenesis via modulation of wnt signaling. Stem Cell Reports 2019; 12(6):1313-28.
  7. Faure A, Verret L, Bozon B, El Tannir El Tayara N, Ly M, Kober F, et al. Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease. Neurobiol Aging 2011; 32(3):407-18.
  8. Zielińska MA, Białecka A, Pietruszka B, Hamułka J. Vegetables and fruit, as a source of bioactive substances, and impact on memory and cognitive function of elderly. Postepy Hig Med Dosw (Online) 2017; 71:267-80.
  9. Fani M, Mohammadipour A, Ebrahimzadeh-Bideskan A. The effect of crocin on testicular tissue and sperm parameters of mice offspring from mothers exposed to atrazine during pregnancy and lactation periods: An experimental study. Int J Reprod Biomed 2018; 16(8):519-28.
  10. Haeri P, Mohammadipour A, Heidari Z, Ebrahimzadeh-Bideskan A. Neuroprotective effect of crocin on substantia nigra in MPTP-induced Parkinson's disease model of mice. Anat Sci Int 2019; 94(1):119-27.
  11. Baghishani F, Mohammadipour A, Hosseinzadeh H, Hosseini M, Ebrahimzadeh-Bideskan A. The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Metab Brain Dis 2018; 33(3):907-16.
  12. Farshid A, Tamaddonfard E. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats. Avicenna J Phytomed 2015; 5(5):469-78.
  13. Sarshoori JR, Asadi MH, Mohammadi MT. Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat. Iran J Basic Med Sci 2014; 17(11):895-902.
  14. Asadi F, Jamshidi AH, Khodagholi F, Yans A, Azimi L, Faizi M, et al. Reversal effects of crocin on amyloid β-induced memory deficit: modification of autophagy or apoptosis markers. Pharmacol Biochem Behav 2015; 139(Pt A):47-58.
  15. Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi S, Khosravi V, Rahman B, et al. Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats. Iran J Basic Med Sci 2013; 16(1):91-100.
  16. Abe K, Saito H. Effects of saffron extract and its constituent crocin on learning behaviour and long‐term potentiation. Phytother Res 2000; 14(3):149-52.
  17. Motaghinejad M, Safari S, Feizipour S, Sadr S. Crocin may be useful to prevent or treatment of alcohol induced neurodegeneration and neurobehavioral sequels via modulation of CREB/BDNF and Akt/GSK signaling pathway. Med Hypotheses 2019; 124:21-5.
  18. Dorri SA, Hosseinzadeh H, Abnous K, Hasani FV, Robati RY, Razavi BM. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iran J Basic Med Sci 2015; 18(10):958-66.
  19. Seo HS, Yang M, Song MS, Kim JS, Kim SH, Kim JC, et al. Toluene inhibits hippocampal neurogenesis in adult mice. Pharmacol Biochem Behav 2010; 94(4):588-94.
  20. Couillard‐Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 2005; 21(1):1-14.
  21. Hai J, Su SH, Lin Q, Zhang L, Wan JF, Li H, et al. Cognitive impairment and changes of neuronal plasticity in rats of chronic cerebral hypoperfusion associated with cerebral arteriovenous malformations. Acta Neurol Belg 2010; 110(2):180-5.
  22. Wang Y, Chen W, Hou B, Gao Y, Li Z, Li X, et al. Altered expression of thrombospondin-1/-2 in the cortex and synaptophysin in the hippocampus after middle cerebral artery occlusion and reperfusion. Int J Clin Exp Pathol 2018; 11(7):3267-76.
  23. Robinson JL, Molina-Porcel L, Corrada MM, Raible K, Lee EB, Lee VM, et al. Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest-old. Brain 2014; 137(Pt 9):2578-87.
  24. Bigham M, Mohammadipour A, Hosseini M, Malvandi AM, Ebrahimzadeh-Bideskan A. Neuroprotective effects of garlic extract on dopaminergic neurons of substantia nigra in a rat model of Parkinson's disease: motor and non-motor outcomes. Metab Brain Dis 2021; 36(5):927-37.
  25. Yang SQ, Tian Q, Li D, He SQ, Hu M, Liu SY, et al. Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect. Neurochem Int 2020; 135:104692.
  26. Heidari Z, Mohammadipour A, Haeri P, Ebrahimzadeh-Bideskan A. The effect of titanium dioxide nanoparticles on mice midbrain substantia nigra. Iran J Basic Med Sci 2019; 22(7):745-51.
  27. Karimooy FN, Bideskan AE, Pour AM, Hoseini SM. Neurotoxic effects of stanozolol on male rats' hippocampi: does stanozolol cause apoptosis? Biomol Concepts 2019; 10(1):73-81.
  28. Baradaran R, Khoshdel-Sarkarizi H, Kargozar S, Hami J, Mohammadipour A, Sadr-Nabavi A, et al. Developmental regulation and lateralisation of the α7 and α4 subunits of nicotinic acetylcholine receptors in developing rat hippocampus. Int J Dev Neurosci 2020; 80(4):303-18.
  29. Abbasi F, Baradaran R, Khoshdel-Sarkarizi H, Kargozar S, Hami J. Mohammadipour A, et al. Distribution pattern of nicotinic acetylcholine receptors in developing cerebellum of rat neonates born of diabetic mothers. J Chem Neuroanat 2020; 108:101819.
  30. Khoshdel-Sarkarizi H, Hami J, Mohammadipour A, Sadr-Nabavi A, Mahmoudi M, Kheradmand H, et al. Developmental regulation and lateralization of GABA receptors in the rat hippocampus. Int J Dev Neurosci 2019; 76:86-94.
  31. Vilar M, Mira H. Regulation of neurogenesis by neurotrophins during adulthood: expected and unexpected roles. Front Neurosci 2016; 10:26.
  32. Hassani FV, Naseri V, Razavi BM, Mehri S, Abnous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru 2014; 22(1):16.
  33. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4(4):299-309.
  34. Ng YP, Wu Z, Wise H, Tsim KW, Wong YH, Ip NY. Differential and synergistic effect of nerve growth factor and cAMP on the regulation of early response genes during neuronal differentiation. Neurosignals 2009; 17(2):111-20.
  35. Ergin V, Erdogan M, Menese A. Regulation of shootin1 gene expression involves ngf-induced alternative splicing during neuronal differentiation of PC12 cells. Scientific Reports 2015; 5:17931.
  36. Scardigli R, Capelli P, Vignone D, Brandi R, Ceci M, La F, et al. Neutralization of nerve growth factor impairs proliferation and differentiation of adult neural progenitors in the subventricular zone. Stem Cells 2014; 32(9):2516-28.
  37. Colangelo AM, Follesa P, Mocchetti I. Differential induction of nerve growth factor and basic fibroblast growth factor mRNA in neonatal and aged rat brain. Brain Res Mol Brain Res 1998; 53(1-2):218-25.
  38. Herold S, Jagasia R, Merz K, Wassmer K, Lie DC. CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventricular zone neurogenesis. Mol Cell Neurosci 2011; 46(1):79-88.
  39. Baptista P, Andrade JP. Adult hippocampal neurogenesis: regulation and possible functional and clinical correlates. Front Neuroanat 2018; 12:44.
  40. Mohammadipour A, Haghir H, Ebrahimzadeh Bideskan A. A link between nanoparticles and Parkinson's disease. Which nanoparticles are most harmful? Rev Environ Health 2020; 35(4):545-56.
  41. Soleimani S, Pirmoradloo E, Farmani F, Moein S, Yousefzadi M. Antidiabetic and Antioxidant Properties of Sea Urchin Echinometra mathaei from the Persian Gulf. Journal of Kerman University of Medical Sciences. 2021; 28(1):104-115.
  42. Akbari M, Dabiri S, Moeini-Aghtaei M, Nazari-Robati M. Thermostabilized chondroitinase ABC Promotes Neuroprotection after Contusion Spinal Cord Injury. Journal of Kerman University of Medical Sciences 2020; 27(5):369-379.
  43. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, et al. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol 2011; 667(1-3):222-9.
  44. Ito N, Yabe T, Gamo Y, Nagai T, Oikawa T, Yamada H, et al. Icv administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation. Neuroscience 2008; 157(4):720-32.
  45. Mavanji V, Butterick TA, Duffy CM, Nixon JP, Billington CJ, Kotz CM. Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice. Neurobiol Learn Mem 2017; 146:21-30.
  46. Chen XY, Chen L, Du YF. Orexin‐A increases the firing activity of hippocampal CA1 neurons through orexin‐1 receptors. J Neurosci Res 2017; 95(7):1415-26.
  47. Xu L, Long J, Su Z, Xu B, Lin M, Chen Y, et al. Restored presynaptic synaptophysin and cholinergic inputs contribute to the protective effects of physical running on spatial memory in aged mice. Neurobiol Dis 2019; 132:104586.
  48. Nemes AD, Ayasoufi K, Ying Z, Zhou QG, Suh H, Najm IM. Growth associated protein 43 (GAP-43) as a novel target for the diagnosis, treatment and prevention of epileptogenesis. Scientific Reports 2017; 7:17702.
  49. Alkadhi KA. Cellular and molecular differences between area ca1 and the dentate gyrus of the hippocampus. Mol Neurobiol 2019; 56(9):6566-80.
  50. Mercer A, Thomson AM. Cornu ammonis regions-antecedents of cortical layers? Front Neuroanat 2017; 11:83.

Journal of Kerman University of Medical Sciences
Volume 28, Issue 3
May and June 2021
Pages 243-251

Home

Editorial Board

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us