Dietary restriction prevents dendritic changes of pyramidal neurons in hippocampal and prefrontal cortex in diabetic rat

Document Type : Research Paper


1 School of Medicine, Shahed University, Tehran, Iran

2 Department of Anatomy, School of Medicine, Shahed University, Tehran, Iran.

3 Neurophysiology Research Center, Shahed University, Tehran, Iran


Background and Objective: Diabetes mellitus (DM) is a common endocrine disorder with cognition decline. Dietary restriction (DR), also known as calorie restriction (CR), and reduction of foodstuff intake in rodents result in increased lifespan with protective potential. The aim of this study was to analyze the effect of DR on dendritic spine loss in streptozotocin (STZ) diabetic rats.
Materials and Methods: Rats were grouped into control, diabetic, and diabetic with DR. For induction of diabetes, STZ (i.p.) at a dose of 60 mg/kg was used. DR was applied from one month before till 2 months after diabetes induction. Finally, dendritic changes of pyramidal neurons in hippocampal and prefrontal cortex were assessed using Golgi impregnation method.
Results: Our histochemical findings showed a significant reduction of dendritic mushroom spines of pyramidal neurons of hippocampal CA1 and prefrontal areas in the diabetic rats that was significantly attenuated in the presence of DR.
Conclusion: DR application could appropriately prevent dendritic spine loss and in this way may have a beneficial effect on cognitive abilities in diabetic condition.


  1. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science (New York, N.Y.) 2010;328(5976):321-6.
  2. Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, et al. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes 2013;62(9):3027-32.
  3. Weiss EP, Fontana L. Caloric restriction: powerful protection for the aging heart and vasculature. American journal of physiology. Heart and circulatory physiology 2011;301(4):H1205-19.
  4. Pallavi R, Giorgio M, Pelicci PG. Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life. Frontiers in Physiology 2012;3:318.
  5. Willette AA, Coe CL, Colman RJ, Bendlin BB, Kastman EK, Field AS, et al. Calorie restriction reduces psychological stress reactivity and its association with brain volume and microstructure in aged rhesus monkeys. Psychoneuroendocrinology 2012;37(7):903-16.
  6. Sandhir R, Gupta S. Molecular and biochemical trajectories from diabetes to Alzheimer's disease: A critical appraisal. World Journal of Diabetes 2015;6(12):1223-42.
  7. Fradkin JE, Cowie CC, Hanlon MC, Rodgers GP. Celebrating 30 years of research accomplishments of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes 2013;62(12):3963-7.
  8. Rathmann W, Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(10):2568-9; author reply 9.
  9. Zhou Y, Luo Y, Dai J. Axonal and dendritic changes are associated with diabetic encephalopathy in rats: an important risk factor for Alzheimer's disease. Journal of Alzheimer's disease : JAD 2013;34(4):937-47.
  10. Joghataie MT, Roghani M, Jalali MR, Baluchnejadmojarad T, Sharayeli M. Dendritic spine changes in medial prefrontal cortex of male diabetic rats using Golgi-impregnation method. Archives of Iranian Medicine 2007;10(1):54-8.
  11. Fallahi F, Roghani M, Moghadami S. Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats. Indian Journal of Pharmacology 2012;44(3):382-6.
  12. Roghani-Dehkordi F, Roghani M, Baluchnejadmojarad T. Diosgenin Mitigates Streptozotocin Diabetes-induced Vascular Dysfunction of the Rat Aorta: The Involved Mechanisms. Journal of Cardiovascular Pharmacology 2015;66(6):584-92.
  13. Roghani M, Taghi Joghataie M, Jalali Nadoushan MR, Baluchnejadmojarad T, Roghani Dehkordi F. Morphological Changes in Hippocampal Ca1 Area in Diabetic Rats: A Golgi-impregnation Study. Iranian Journal of Pathology 2006;1(4):135-40.
  14. Harris Y, Gorelick PB, Freels S, Billingsley M, Brown N, Robinson D. Neuroepidemiology of vascular and Alzheimer's dementia among African-American women. Journal of the National Medical Association 1995;87(10):741-5.
  15. Parihar MS, Chaudhary M, Shetty R, Hemnani T. Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera. Journal of Clinical Neuroscience 2004;11(4):397-402.
  16. Kalalian-Moghaddam H, Baluchnejadmojarad T, Roghani M, Goshadrou F, Ronaghi A. Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats. European Journal of Pharmacology 2013;698(1-3):259-66.
  17. Nitta A, Murai R, Suzuki N, Ito H, Nomoto H, Katoh G, et al. Diabetic neuropathies in brain are induced by deficiency of BDNF. Neurotoxicology and Teratology 2002;24(5):695-701.
  18. Gregosa A, Vinuesa A, Todero MF, Pomilio C, Rossi SP, Bentivegna M, et al. Periodic dietary restriction ameliorates amyloid pathology and cognitive impairment in PDAPP-J20 mice: Potential implication of glial autophagy. Neurobiology of Disease 2019:104542.
  19. Mattson MP. Energy intake, meal frequency, and health: a neurobiological perspective. Annual Review of Nutrition 2005;25(1):237-60.
  20. Liu Y, Wang R, Zhao Z, Dong W, Zhang X, Chen X, et al. Short-term caloric restriction exerts neuroprotective effects following mild traumatic brain injury by promoting autophagy and inhibiting astrocyte activation. Behavioral Brain Research 2017;331:135-42.
  21. Ma L, Wang R, Dong W, Zhao Z. Caloric restriction can improve learning and memory in C57/BL mice probably via regulation of the AMPK signaling pathway. Experimental Gerontology 2018;102:28-35.
  22. Moroi-Fetters SE, Mervis RF, London ED, Ingram DK. Dietary restriction suppresses age-related changes in dendritic spines. Neurobiology of Aging 1989;10(4):317-22.
  23. Hadem IKH, Sharma R. Differential Regulation of Hippocampal IGF-1-Associated Signaling Proteins by Dietary Restriction in Aging Mouse. Cellular and Molecular Neurobiology 2017;37(6):985-93.
  24. Goyary D, Sharma R. Dietary restriction prevents diabetogenic effect of streptozotocin in mice. Indian Journal of Biochemistry & Biophysics 2010;47(4):254-6.