Abstract
Microgliosis and inflammation are major wrongdoers in cypermethrin-induced Parkinsonism along with oxidative stress, mitochondrial dysfunction and α-synuclein aggregation. Dopamine depletion could alter dendritic morphology, length and spine number in the striatum. Present study investigated the effect of ibuprofen on the dendritic morphology, length and spine density in cypermethrin PD model. Male pups were treated intraperitoneally with cypermethrin during postnatal days followed by adulthood to induce Parkinsonism using standard procedure along with controls. Subsets of animals were pre-treated with ibuprofen 2 h prior to cypermethrin treatment during adulthood. Standard methods were used to confirm Parkinsonism/neuroprotection. Striatal dendritic morphology, length, spine number and expression of synaptophysin and postsynaptic density protein-95 (PSD-95) along with the nigrostriatal pro-inflammatory and apoptotic proteins were measured. Cypermethrin induced Parkinsonian traits and attenuated the dendritic length, spine number and expression of synaptophysin and PSD-95. While cypermethrin increased the expression of interleukin-1β, interleukin-4, interferon-γ, inducible nitric oxide synthase, caspase-3, caspase-9 and B-cell lymphoma (Bcl)-xl proteins, it attenuated Bcl-2 expression. Ibuprofen normalized the changes in dendritic morphology, length, spine number and expression of synaptophysin, PSD-95, and pro-inflammatory and apoptotic proteins. Results demonstrate that cypermethrin induces inflammation and alters dendritic morphology, length and spine number, which are encountered by ibuprofen.
Similar content being viewed by others
References
Singh AK, Tiwari MN, Prakash O, Singh MP (2012a) A current review of cypermethrin-induced neurotoxicity and nigrostriatal dopaminergic neurodegeneration. Curr Neuropharmacol 10:64–71
Mishra AK, Ur Rasheed MS, Shukla S, Tripathi MK, Dixit A, Singh MP (2015) Aberrant autophagy and Parkinsonism: does correction rescue from disease progression? Mol Neurobiol 51:893–908
Galli S, Lopes DM, Ammari R, Kopra J, Millar SE, Gibb A, Salinas PC (2014) Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice. Nat Commun 5:4992
Tripathi P, Singh A, Agrawal S, Prakash O, Singh MP (2014) Cypermethrin alters the status of oxidative stress in the peripheral blood: relevance to Parkinsonism. J Physiol Biochem 70:915–924
Singh AK, Tiwari MN, Upadhyay G, Patel DK, Singh D, Prakash O, Singh MP (2012b) Long term exposure to cypermethrin induces nigrostriatal dopaminergic neurodegeneration in adult rats: Postnatal exposure enhances the susceptibility during adulthood. Neurobiol Aging 33:404–415
Bartels AL, Leenders KL (2010) Cyclooxygenase and neuroinflammation in Parkinson's disease neurodegeneration. Curr Neuropharmacol 8:62–68
Tavosanis G (2012) Dendritic structural plasticity. Inc Develop Neurobiol 72:73–86
Hsieh YC, Mounsey RB, Teismann P (2011) MPP+-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress. Naunyn Schmiedeberg's Arch Pharmacol 384:157–167
Singh A, Tripathi P, Prakash O, Singh MP (2016) Ibuprofen abates cypermethrin-induced expression of pro-inflammatory mediators and mitogen-activated protein kinases and averts the nigrostriatal dopaminergic neurodegeneration. Mol Neurobiol 53:6849–6858
Kaufmann WE, Worley PF, Pegg J, Bremer M, Isakson P (1996) COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Natl Acad Sci U S A 93:2317–2321
Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (2002) Regulation of synaptophysin degradation by mammalian homologues of seven in absentia. J Biol Chem 277:10273–10282
Marquèze-Pouey B, Wisden W, Malosio ML, Betz H (1991) Differential expression of synaptophysin and synaptoporin mRNAs in the postnatal rat central nervous system. J Neurosci 1991:3388–33897
Wiedenmann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell 41:1017–1028
Han K, Kim E (2008) Synaptic adhesion molecules and PSD-95. Prog Neurobiol 84:263–283
Toy WA, Petzinger GM, Leyshon BJ, Akopian GK, Walsh JP, Hoffman MV, Vučković MG, Jakowec MW (2014) Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Neurobiol Dis 63:201–209
Shin MS, Jeong HY, An DI, Lee HY, Sung YH (2016) Treadmill exercise facilitates synaptic plasticity on dopaminergic neurons and fibers in the mouse model with Parkinson’s disease. Neurosci Lett 621:28–33
Singh AK, Tiwari MN, Dixit A, Upadhyay G, Patel DK, Singh D, Prakash O, Singh MP (2011) Nigrostriatal proteomics of cypermethrin-induced dopaminergic neurodegeneration: microglial activation-dependent and -independent regulations. Toxicol Sci 122:526–538
Tareke E, Bowyer JF, Doerge DR (2007) Quantification of rat brain neurotransmitters and metabolites using liquid chromatography/electrospraytandem mass spectrometry and comparison with liquid chromatography/electrochemical detection. Rapid Commun Mass Spectrom 21(23):3898–3904
Naskar A, Manivasagam T, Chakraborty J, Singh R, Thomas B, Dhanasekaran M, Mohanakumar KP (2013) Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism. J Pineal Res 55:304–312
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Agrawal S, Dixit A, Singh A, Tripathi P, Singh D, Patel DK, Singh MP (2015a) Cyclosporine a and MnTMPyP alleviate α-synuclein expression and aggregation in cypermethrin-induced Parkinsonism. Mol Neurobiol 52:1619–1628
Agrawal S, Singh A, Tripathi P, Mishra M, Singh PK, Singh MP (2015b) Cypermethrin-induced nigrostriatal dopaminergic neurodegeneration alters the mitochondrial function: A proteomics study. Mol Neurobiol 51:448–465
Soderstrom KE, O'Malley JA, Levine ND, Sortwell CE, Collier TJ, Steece-Collier K (2010) Impact of dendritic spine preservation in medium spiny neurons on dopamine graft efficacy and the expression of dyskinesias in Parkinsonian rats. Eur J Neurosci 3:478–490
Villalba RM, Smith Y (2013) Differential striatal spine pathology in Parkinson’s disease and cocaine addiction: a key role of dopamine? Neuroscience 251:2–20
Alamdary SZ, Digaleh H, Khodagholi F (2013) Dual contradictory effect of H-89 on neuronal retraction, death and inflammation in differentiated PC12 cells subjected to oxidative stress. J Mol Neurosci 51:1030–1037
Lin WM, Zhang YM, Moldzio R, Rausch WD (2007) Ginsenoside Rd attenuates neuroinflammation of dopaminergic cells in culture. J Neural Transm Suppl 72:105–112
Bai X, Strong R (2014) Expression of synaptophysin protein in different dopaminergic cell lines. J Biochem Pharmacol Res 2:185–190
El-Husseini AE, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1364–1368
Acknowledgements
Authors recognize the Council of Scientific and Industrial Research (CSIR), India for the financial support to the study (CSIR Network Project: BSC0115/miND). Indian Council of Medical Research, India, is gratefully acknowledged for extending the fellowship to Pratibha Tripathi and Ashish Singh. The CSIR-IITR communication number of this article is 3450.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tripathi, P., Singh, A., Bala, L. et al. Ibuprofen Protects from Cypermethrin-Induced Changes in the Striatal Dendritic Length and Spine Density. Mol Neurobiol 55, 2333–2339 (2018). https://doi.org/10.1007/s12035-017-0491-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-017-0491-9