Metabolic Brain Disease

, Volume 33, Issue 5, pp 1761–1774 | Cite as

Calorie restriction protects against apoptosis, mitochondrial oxidative stress and increased calcium signaling through inhibition of TRPV1 channel in the hippocampus and dorsal root ganglion of rats

  • Fatih Gültekin
  • Mustafa NazıroğluEmail author
  • Hasan Basri Savaş
  • Bilal Çiğ
Original Article


The TRPV1 channel is activated in neurons by capsaicin, oxidative stress, acidic pH and heat factors, and these factors are attenuated by the antioxidant role of calorie restriction (CR). Hence, we investigated the hypothesis that the antioxidant roles of CR and food frequency (FF) may modulate TRPV1 activity and apoptosis through inhibition of mitochondrial oxidative stress in hippocampal (HIPPON) and dorsal root ganglion neurons (DRGN). We investigated the contribution of FF and CR to neuronal injury and apoptosis through inhibition of TRPV1 in rats. We assigned rats to control, FF and FF + CR groups. A fixed amount of food ad libitum was supplemented to the control and FF groups for 20 weeks, respectively. FF + CR group were fed the same amount of food as the control group but with 20% less calories during the same period. In major results, TRPV1 currents, intracellular Ca2+ levels, apoptosis, reactive oxygen species, mitochondrial depolarization, PARP-1 expression, caspase 3 and 9 activity and expression values were found to be increased in the HIPPON and DRGN following FF treatment, and these effects were decreased following FF + CR treatment. The FF-induced decrease in cell viability of HIPPO and DRGN, and vitamin E concentration of brain, glutathione peroxidase, vitamin A, and β-carotene values of the HIPPO, DRGN, plasma, liver and kidney were increased by FF + DR treatment, although lipid peroxidation levels in the same samples were decreased. In conclusion, CR reduces FF-induced increase of oxidative stress, apoptosis and Ca2+ entry through TRPV1 in the HIPPON and DRGN. Our findings may be relevant to the etiology and treatment of obesity following CR treatment.


Apoptosis Calorie restriction Food frequency Oxidative stress TRPV1 channel 



intracellular free calcium ion






calorie restriction




dorsal root ganglion neuron


food frequency


glutathione peroxidase


reduced glutathione


hippocampal neuron




Poly-ADPR polymerase 1


reactive oxygen species


transient receptor potential


transient receptor potential vanilloid 1


whole cell



The abstract of the study will be published in the 2nd International Brain Research School, 6-12 November 2017, Isparta, Turkey ( The study was supported by the Scientific Project Unit of Alanya Alaaddin Keykubat University (Protocol No: 2017-04-01-MAP01). All authors approved the final manuscript. There is no disclosure for the current study. MN and FG formulated the present hypothesis and were responsible for writing the report. HBŞ was responsible for animal experiments. BÇ was responsible for isolation of HIPPO and DRGN and analyses of intracellular Ca2+ concentration. The authors wish to thank Dr. Nady Braidy (School of Psychiatry, Faculty of Medicine, University of New South Wales, Randwick, Australia) and technician Fatih Şahin (Neuroscience Research Center, SDU, Isparta, Turkey) for helping with patch-clamp and polishing English, respectively.

Compliance with ethical standards


None of the authors have any to disclose. All authors approved the final manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fatih Gültekin
    • 1
  • Mustafa Nazıroğlu
    • 2
    • 3
    Email author
  • Hasan Basri Savaş
    • 4
  • Bilal Çiğ
    • 3
  1. 1.Department of Clinical Biochemistry, Faculty of MedicineUniversity of Health SciencesIstanbulTurkey
  2. 2.Neuroscience Research CenterSuleyman Demirel UniversityIspartaTurkey
  3. 3.Department of Biophysics, Faculty of MedicineSuleyman Demirel UniversityIspartaTurkey
  4. 4.Department of Clinical Biochemistry, Faculty of MedicineAlanya Alaaddin Keykubat UniversityAntalyaTurkey

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