Abstract
Foraging behavior is a species-specific behavior which is considered to involve the decision making and higher cognitive functions. We previously established a novel method to detect the foraging behavior in chronic unpredictable mild stress (CUMS)-induced depression mice, in which the food foraging activity of mice was significantly reduced. Furthermore, it is generally assumed that the bilateral anterior cingulate cortex (ACC) is related to foraging activity in rat. Brain-derived neurotrophic factor (BDNF) is widely expressed in many regions of the brain and is down-regulated in depressive patients. However, the relationship between the precursor of brain-derived neurotrophic factor (proBDNF) and depression has not been fully elucidated. The results showed that CUMS in mice induced anxiety- and depression-like behaviors and significant reduction in BDNF messenger RNA (mRNA) in the brain. In this study, we evaluated the effect of anti-BDNF and anti-proBDNF in the ACC on the CUMS-induced depression mice. In contrast to the normal IgG group (normal IgG microinjection into the ACC), bilateral ACC treatment with anti-proBDNF microinjection not only reversed depressive activity but also significantly increased the amount of foraged food and BDNF mRNA in the brain. There was no significant alteration in the group of anti-BDNF microinjection into the ACC. Our data indicate that the proBDNF signaling pathway might down-regulate the foraging activity in CUMS rodents and be involved in the depression.
Similar content being viewed by others
References
Bai YY, Ruan CS, Yang CR, Li JY, Kang ZL, Zhou L, Liu D, Zeng YQ, Wang TH, Tian CF, Liao H, Bobrovskaya L, Zhou XF (2016) ProBDNF signaling regulates depression-like behaviors in rodents under chronic stress. Neuropsychopharmacology
Bambico FR, Belzung C (2013) Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis? Curr Top Behav Neurosci 15:243–291
Barker PA (2009) Whither proBDNF? Nat Neurosci 12(2):105–106
Bartness TJ, Keen-Rhinehart E, Dailey MJ, Teubner BJ (2011) Neural and hormonal control of food hoarding. Am J Physiol Regul Integr Comp Physiol 301(3):R641–R655
Beilharz JE, Maniam J, Morris MJ (2015) Diet-induced cognitive deficits: the role of fat and sugar, potential mechanisms and nutritional interventions. Nutrients 7(8):6719–6738
Bissiere S, McAllister KH, Olpe HR, Cryan JF (2006) The rostral anterior cingulate cortex modulates depression but not anxiety-related behaviour in the rat. Behav Brain Res 175(1):195–199
Blokland A, Lieben C, Deutz NE (2002) Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat. J Psychopharmacol 16(1):39–49
Cheng Y, Su Q, Shao B, Cheng J, Wang H, Wang L, Lin Z, Ruan L, ZhuGe Q, Jin K (2013) 17 beta-estradiol attenuates poststroke depression and increases neurogenesis in female ovariectomized rats. Biomed Res Int 2013:392434
Chudasama Y, Daniels TE, Gorrin DP, Rhodes SE, Rudebeck PH, Murray EA (2013) The role of the anterior cingulate cortex in choices based on reward value and reward contingency. Cereb Cortex 23(12):2884–2898
Dai RP, Li CQ, Zhang JW, Li F, Shi XD, Zhang JY, Zhou XF (2011) Biphasic activation of extracellular signal-regulated kinase in anterior cingulate cortex distinctly regulates the development of pain-related anxiety and mechanical hypersensitivity in rats after incision. Anesthesiology 115(3):604–613
Dailey MJ, Bartness TJ (2010) Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding. Brain Res 1323:94–108
Day JJ, Jones JL, Wightman RM, Carelli RM (2010) Phasic nucleus accumbens dopamine release encodes effort- and delay-related costs. Biol Psychiatry 68(3):306–309
Elliott R, Sahakian BJ, McKay AP, Herrod JJ, Robbins TW, Paykel ES (1996) Neuropsychological impairments in unipolar depression: the influence of perceived failure on subsequent performance. Psychol Med 26(5):975–989
Fan YJ, Wu LL, Li HY, Wang YJ, Zhou XF (2008) Differential effects of pro-BDNF on sensory neurons after sciatic nerve transection in neonatal rats. Eur J Neurosci 27(9):2380–2390
Hagan CC, Graham JM, Tait R, Widmer B, van Nieuwenhuizen AO, Ooi C, Whitaker KJ, Simas T, Bullmore ET, Lennox BR, Sahakian BJ, Goodyer IM, Suckling J (2015) Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus. Neuroimage Clin 7:391–399
Hariri AR, Goldberg TE, Mattay VS, Kolachana BS, Callicott JH, Egan MF, Weinberger DR (2003) Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 23(17):6690–6694
Holec V, Pirot HL, Euston DR (2014) Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions. Front Behav Neurosci 8:12
Holroyd CB, Yeung N (2012) Motivation of extended behaviors by anterior cingulate cortex. Trends Cogn Sci 16(2):122–128
Jiang C, Salton SR (2013) The role of neurotrophins in major depressive disorder. Transl Neurosci 4(1):46–58
Juric DM, Miklic S, Carman-Krzan M (2006) Monoaminergic neuronal activity up-regulates BDNF synthesis in cultured neonatal rat astrocytes. Brain Res 1108(1):54–62
Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109(2):143–148
Kennerley SW, Walton ME, Behrens TE, Buckley MJ, Rushworth MF (2006) Optimal decision making and the anterior cingulate cortex. Nat Neurosci 9(7):940–947
Kong H, Zeng XN, Fan Y, Yuan ST, Ge S, Xie WP, Wang H, Hu G (2014) Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis. CNS Neurosci Ther 20(5):391–402
Kutiyanawalla A, Terry AV Jr, Pillai A (2011) Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment. PLoS One 6(10):e26153
Lee BH, Kim H, Park SH, Kim YK (2007) Decreased plasma BDNF level in depressive patients. J Affect Disord 101(1–3):239–244
Li F, Li M, Cao W, Xu Y, Luo Y, Zhong X, Zhang J, Dai R, Zhou XF, Li Z, Li C (2012a) Anterior cingulate cortical lesion attenuates food foraging in rats. Brain Res Bull 88(6):602–608
Li F, Cao WY, Li MB, Xu Y, Zhang JW, Zhang JY, Luo XG, Dai RP, Zhou XF, Li CQ (2012b) A simple method for detection of food foraging behavior in the rat: involvement of NMDA and dopamine receptors in the behavior. Neuroscience 205:73–80
Macedo IC, Rozisky JR, Oliveira C, Oliveira CM, Laste G, Nonose Y, Santos VS, Marques PR, Ribeiro MF, Caumo W, Torres IL (2015) Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats. Neuropeptides 51:75–81
Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, Murphy RA (2001) Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem 276(16):12660–12666
Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E (2005) Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 53(2):129–139
O’Brien JT, Lloyd A, McKeith I, Gholkar A, Ferrier N (2004) A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry 161(11):2081–2090
Pang PT, Teng HK, Zaitsev E, Woo NT, Sakata K, Zhen S, Teng KK, Yung WH, Hempstead BL, Lu B (2004) Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306(5695):487–491
Panza F, Frisardi V, Capurso C, D’Introno A, Colacicco AM, Imbimbo BP, Santamato A, Vendemiale G, Seripa D, Pilotto A, Capurso A, Solfrizzi V (2010) Late-life depression, mild cognitive impairment, and dementia: possible continuum? Am J Geriatr Psychiatry 18(2):98–116
Patricio P, Mateus-Pinheiro A, Sousa N, Pinto L (2013) Re-cycling paradigms: cell cycle regulation in adult hippocampal neurogenesis and implications for depression. Mol Neurobiol 48(1):84–96
Pollak DD, Rey CE, Monje FJ (2010) Rodent models in depression research: classical strategies and new directions. Ann Med 42(4):252–264
Richard E, Reitz C, Honig LH, Schupf N, Tang MX, Manly JJ, Mayeux R, Devanand D, Luchsinger JA (2013) Late-life depression, mild cognitive impairment, and dementia. JAMA Neurol 70(3):374–382
Ruan CS, Wang SF, Shen YJ, Guo Y, Yang CR, Zhou FH, Tan LT, Zhou L, Liu JJ, Wang WY, Xiao ZC, Zhou XF (2014) Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress. Eur J Neurosci 40(4):2680–2690
Ruan CS, Zhou FH, He ZY, Wang SF, Yang CR, Shen YJ, Guo Y, Zhao HB, Chen L, Liu D, Liu J, Baune BT, Xiao ZC, Zhou XF (2015) Mice deficient for wild-type p53-induced phosphatase 1 display elevated anxiety- and depression-like behaviors. Neuroscience 293:12–22
Rudebeck PH, Bannerman DM, Rushworth MF (2008) The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making. Cogn Affect Behav Neurosci 8(4):485–497
Sartori Oliveira CE, Gai BM, Godoi B, Zeni G, Nogueira CW (2012) The antidepressant-like action of a simple selenium-containing molecule, methyl phenyl selenide, in mice. Eur J Pharmacol 690(1–3):119–123
Shen X, Xu GZ (2007) Effect of interleukin-1 beta on glutamine synthetase in rat retinal Müller cell under high glucose conditions. Zhonghua Yan Ke Za Zhi 43(8):744–749
Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K (2015) Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist. Eur Neuropsychopharmacol
Su CL, Su CW, Hsiao YH, Gean PW (2016) Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. J Psychiatr Res 76:101–110
Sun Y, Lim Y, Li F, Liu S, Lu JJ, Haberberger R, Zhong JH, Zhou XF (2012) ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA. PLoS One 7(4):e35883
Svenningsson P, Tzavara ET, Qi H, Carruthers R, Witkin JM, Nomikos GG, Greengard P (2007) Biochemical and behavioral evidence for antidepressant-like effects of 5-HT6 receptor stimulation. J Neurosci 27(15):4201–4209
Swiergiel AH, Dunn AJ (2007) Effects of interleukin-1beta and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests. Pharmacol Biochem Behav 86(4):651–659
Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83(3):482–504
Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8(8):1069–1077
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6(7):736–742
Xu ZQ, Sun Y, Li HY, Lim Y, Zhong JH, Zhou XF (2011) Endogenous proBDNF is a negative regulator of migration of cerebellar granule cells in neonatal mice. Eur J Neurosci 33(8):1376–1384
Yang J, Harte-Hargrove LC, Siao CJ, Marinic T, Clarke R, Ma Q, Jing D, Lafrancois JJ, Bath KG, Mark W, Ballon D, Lee FS, Scharfman HE, Hempstead BL (2014a) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep 7(3):796–806
Yang CR, Zhang ZG, Bai YY, Zhou HF, Zhou L, Ruan CS, Li F, Li CQ, Zheng HY, Shen LJ, Zhou XF (2014b) Foraging activity is reduced in a mouse model of depression. Neurotox Res 25(3):235–247
Yang CR, Bai YY, Ruan CS, Zhou HF, Liu D, Wang XF, Shen LJ, Zheng HY, Zhou XF (2015) Enhanced aggressive behaviour in a mouse model of depression. Neurotox Res 27(2):129–142
Yoshida T, Ishikawa M, Niitsu T, Nakazato M, Watanabe H, Shiraishi T, Shiina A, Hashimoto T, Kanahara N, Hasegawa T, Enohara M, Kimura A, Iyo M, Hashimoto K (2012) Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS One 7(8):e42676
Zhang F, Luo J, Min S, Ren L, Qin P (2016) Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats. Brain Res
Zhong XL, Wei R, Zhou P, Luo YW, Wang XQ, Duan J, Bi FF, Zhang JY, Li CQ, Dai RP, Li F (2012) Activation of anterior cingulate cortex extracellular signal-regulated kinase-1 and -2 (ERK1/2) regulates acetic acid-induced, pain-related anxiety in adult female mice. Acta Histochem Cytochem 45(4):219–225
Zhou XF, Song XY, Zhong JH, Barati S, Zhou FH, Johnson SM (2004) Distribution and localization of pro-brain-derived neurotrophic factor-like immunoreactivity in the peripheral and central nervous system of the adult rat. J Neurochem 91(3):704–715
Zhou L, Xiong J, Lim Y, Ruan Y, Huang C, Zhu Y, Zhong JH, Xiao Z, Zhou XF (2013) Upregulation of blood proBDNF and its receptors in major depression. J Affect Disord 150(3):776–784
Acknowledgements
The animal experimental work was done in Kunming Medical University (KMU) and supported by a MOST grant 2011CB944200 and NHMRC grants APP1021408 and APP1021409. X.F.Z. is a visiting professor of KMU. F.H. Zhou was supported by NHMRC overseas bio-medical training fellowship.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
All animal ethics protocols were approved by KMU and met the standards of the Guide for Care and Use of Laboratory Animals established by the National Institutes of Health, USA.
Rights and permissions
About this article
Cite this article
Yang, C.R., Bai, Y.Y., Ruan, C.S. et al. Injection of Anti-proBDNF in Anterior Cingulate Cortex (ACC) Reverses Chronic Stress-Induced Adverse Mood Behaviors in Mice. Neurotox Res 31, 298–308 (2017). https://doi.org/10.1007/s12640-016-9687-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-016-9687-4