Skip to main content
SpringerLink
Log in

Protocatechuic acid attenuate depressive-like behavior in olfactory bulbectomized rat model: behavioral and neurobiochemical investigations

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

The main objective of the present study is to investigate potential effects of PCA in OBX induced depressive-like behavior in rat model. PCA was administered at a dose of 100 mg/kg and 200 mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) expression], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated. Experimental findings reveals that OBX subjected rats showed alteration in behaviors like, increase in immobility time, ambulatory and rearing behaviors significantly, reduced BDNF level, 5-HT, DA,NE and antioxidant parameters along with increased serum corticosterone, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex compared to sham operated rats. Administration of PCA significantly attenuated behavioral and neurobiochemical alterations, thus, its antidepressant-like activity is largely mediated through modulation of neurotransmitter, endocrine and immunologic systems, mainly by improvements of BDNF, 5-HT, DA, NE, reduced MDA, IL-6, and TNF-α in hippocampus and cerebral cortex.

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Antunes MS, Jesse CR, Ruff JR, de Oliveira Espinosa D, Gomes NS, Altvater EET, Donato F, Giacomeli R, Boeira SP (2016) Hesperidin reverses cognitive and depressive disturbances induced by olfactory bulbectomy in mice by modulating hippocampal neurotrophins and cytokine levels and acetylcholinesterase activity. Eur J Pharmacol 789:411–420

    Article  CAS  PubMed  Google Scholar 

  • Cairncross KD, Wren A, Cox B, Schnieden H (1977) Effects of olfactory bulbectomy and domicile on stress-induced corticosterone release in the rat. Physiol Behav 19:485–487

    Article  CAS  PubMed  Google Scholar 

  • Duman RS (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. NeuroMolecular Med 5:11–25

    Article  CAS  PubMed  Google Scholar 

  • Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry 28:435–451

    Article  CAS  PubMed  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–72

    Article  CAS  PubMed  Google Scholar 

  • Fernandes BS, Gama CS, Ceresér KM, Yatham LN, Fries GR, Colpo G et al (2011) Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res 45:995–1004

    Article  PubMed  Google Scholar 

  • Fuchs E, Czéh B, Kole MH et al (2004) Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol 14:S481–S490

    Article  CAS  PubMed  Google Scholar 

  • Jindal A, Mahesh R, Bhatt S (2015a) Type 4 phosphodiesterase enzyme inhibitor, rolipram rescues behavioral deficits in olfactory bulbectomy models of depression: involvement of hypothalamic–pituitary–adrenal axis, cAMP signaling aspects and antioxidant defense system. Pharmacol Biochem Behav 132:20–32

    Article  CAS  PubMed  Google Scholar 

  • Jindal A, Mahesh R, Bhatt S (2015b) Etazolate, a phosphodiesterase-4 enzyme inhibitor produces antidepressant-like effects by blocking the behavioral, biochemical, neurobiological deficits and histological abnormalities in hippocampus region caused by olfactory bulbectomy. Psychopharmacology (Berlin) 232:623–637

    Article  CAS  Google Scholar 

  • Kaster MP, Gadotti VM, Calixto JB (2012) Depressive-like behavior induced by tumor necrosis factor-α in mice. Neuropharmacol 62:419–426

    Article  CAS  Google Scholar 

  • Kim JH, Kim GH, Hwang KH (2012) Monoamine oxidase and dopamine b-hydroxylase inhibitors from the fruits of Gardenia jasminoides. BiomolTher 20:214–219

    CAS  Google Scholar 

  • Kim YS, Seo HW, Lee MH, Kim DK, Jeon H, Cha DS (2014) Protocatechuic acid extends lifespan and increases stress resistance in Caenorhabditis elegans. Archives of Pharmacal Research 37(2):245–252

  • Lovell MA, Xie C, Markesbery WR (1998) Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease. Neurology 51(6):1562–1566

  • Manji HK, Duman RS (2001) Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull l35:5–49

    Google Scholar 

  • Mao Q, Xian YF, Ip SP et al (2010) Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain. Behav Brain Res 210:171–177

    Article  CAS  PubMed  Google Scholar 

  • Mao QQ, Xian YF, Ip SP, Che CT (2011) Involvement of serotonergic system in the antidepressant-like effect of piperine. Prog Neuropsychopharmacol Biol Psychiatry 35:1144–1147

    Article  CAS  PubMed  Google Scholar 

  • Mao QQ, Huang Z, Zhong X et al (2014) Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice. Behav Brain Res 26:140–145

    Article  CAS  Google Scholar 

  • Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, Ruberto A, Tatarelli R, Nicoletti F, Girardi P, Shelton RC (2009) Changes in BDNF serum levels in patients with major depression disorder MDD after 6months treatment with sertraline escitalopram or venlafaxine. J Psychiatr Res 43:247–254

    Article  PubMed  Google Scholar 

  • Muley MM, Thakare VN, Patil RR, Kshirsagar AD, Naik SR (2012) Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: comparative evaluation with piracetam and protocatachuic acid. Pharmacol Biochem Behav 102:286–293

    Article  CAS  PubMed  Google Scholar 

  • Muley MM, Thakare VN, Patil RR, Bafna PA, Naik SR (2013) Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model. Life Sci 93:51–57

    Article  CAS  PubMed  Google Scholar 

  • Numakawa T, Matsumoto T, Numakawa Y, Richards M, Yamawaki S, Kunugi H (2011) Protective Action of Neurotrophic Factors and Estrogen against Oxidative Stress-Mediated Neurodegeneration. Journal of Toxicology 2011:1–12

  • Nutt DJ (2008) Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry 69:4–7

    Article  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468

    Article  CAS  PubMed  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    CAS  PubMed  Google Scholar 

  • Rang HP, Dale MM, Ritter JM, Flower RJ (2007) Selective serotonin reuptake inhibitors. Pharmacology, pp 566. Churchill Livingstone, Elsevier Publication

  • Rinwa P, Kumar A (2014) Panax quinquefolium involves nitric oxide pathway in olfactory bulbectomy rat model. Physiol Behav 129:142–151

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues ALS, Rocha JBT, Mello CF, Souza DO (1996) Effect of perinatal Lead exposure on rat behaviour in open-field and two-Wky avoidance tasks. Basic Clin Pharmacol Toxicol 79:150–156

    Article  CAS  Google Scholar 

  • Rosa JM, Dafre AL, Rodrigues AL (2013) Antidepressant-like responses in the forced swimming test elicited by glutathione and redox modulation. Behavioural Brain Research 253:165–172

  • Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29:201–217

    Article  CAS  PubMed  Google Scholar 

  • Shellenberger MK, Gordon JH (1971) A rapid, simplified procedure for simultaneous assay of norepinephrine, dopamine, and 5-hydroxytryptamine from discrete brain areas. Anal Biochem 39:356–372

    Article  CAS  PubMed  Google Scholar 

  • Shen J, Ma LG, Hu CY, Pei YY, Jin SL, Fang XY, Li YC (2016) Berberine up-regulates the BDNF expression in hippocampus and attenuates corticosterone-induced depressive-like behavior in mice. Neurosci Lett 614:77–82

    Article  CAS  PubMed  Google Scholar 

  • Shi GF, An LJ, Jiang B, Guan SI, Bao YM (2006) Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo. Neurosci Lett 403:206–210

    Article  CAS  PubMed  Google Scholar 

  • Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada SI, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75

    Article  CAS  PubMed  Google Scholar 

  • Song C, Leonard BE (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 29:627–647

    Article  PubMed  Google Scholar 

  • Tang MM, Lin WJ, Pan YQ, Guan XT, Li YC (2016) Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression. Physiol Behav 161:166–173

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Patel BM (2015) Potential targets for the development of novel antidepressants: future perspectives. CNS Neurol Disord Drug Targets 14:270–281

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Dhakane VD, Patel BM (2016) Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus. Pharmacol Rep 68:1020–1027

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Dhakane VD, Patel BM (2017a) Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice. Metab Brain Dis 32:401–413

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Aswar MK, Kulkarni YP, Patil RR, Patel BM (2017b) Silymarin ameliorates experimentally induced depressive like behavior in rats: involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response. Physiol Behav 179:401–410

    Article  CAS  PubMed  Google Scholar 

  • Van Reizen H, Leonard BE (1990) Effects of psychotropic drugs on the behavior and neurochemistry of olfactory bulbectomised rats. Pharmacol Ther 47:21–34

    Article  Google Scholar 

  • Youdim MB, Weinstock M (2004) Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation. Neurotoxicology 25:243–250

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Li G, Szeto S, Chong C, Quan Q et al (2015) Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson's disease. Free Radic Biol Med 84:331–333

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors are grateful to Prof. M. N. Navale, Founder President, STES, Pune, and Dr. R.N. Kane, Principal, Sinhgad Institute of Pharmaceutical Sciences, Lonavala for providing necessary infrastructural facility, and support in the completion of present research work.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Maharashtra, 410401, India

    Vishnu N. Thakare & Rajesh R. Patil

  2. Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, 382 481, India

    Vishnu N. Thakare & Bhoomika M. Patel

  3. Department of Pharmacology, Smt. Kashibai Navale College of Pharmacy, Kondhawa, Pune, Maharashtra, 411048, India

    Anupama A. Suralkar

  4. Research and Development, Astec Life Sciences, Mumbai, Maharashtra, India

    Valmik D. Dhakane

Authors
  1. Vishnu N. Thakare
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajesh R. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anupama A. Suralkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valmik D. Dhakane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bhoomika M. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bhoomika M. Patel.

Ethics declarations

Conflict of interests

The authors declare that there are no conflicts of interest.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thakare, V.N., Patil, R.R., Suralkar, A.A. et al. Protocatechuic acid attenuate depressive-like behavior in olfactory bulbectomized rat model: behavioral and neurobiochemical investigations. Metab Brain Dis 34, 775–787 (2019). https://doi.org/10.1007/s11011-019-00401-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-019-00401-8

Keywords

Search

Navigation