Profilin-2 increased expression and its altered interaction with β-actin in the striatum of 3-nitropropionic acid-induced Huntington's disease in rats

J. Chakraborty, M. Pandey, A. K. Navneet, T. A. Appukuttan, M. Varghese, S. C. Sreetama, U. Rajamma, K. P. Mohanakumar

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Subacute systemic treatment with 3-nitropropionic acid (3-NP) causes specific lesions in the cortex and the striatum, and Huntington's disease behavioral phenotypes in rats. We investigated differentially expressed genes in the striatum, and examined status of a highly expressed huntingtin interacting protein, profilin 2 (Pfn2) in relation to 3-NP-induced striatal neurodegeneration, employing both in vivo animal model and in vitro primary striatal neuronal cultures. Golgi staining of 3-NP-treated rat brain revealed significantly altered dendritic spine morphology and decreased spine density in the cortex and the striatum, as compared to the control. We employed suppression subtractive hybridization (SSH) method to screen differentially expressed genes during striatal neurodegeneration in these animals. Forward and reverse SSH provided a library of 188 clones, which were used for reverse northern dot blot analysis to identify greatly altered striatal-specific genes. Sequence analysis of the clones identified 23 genes, expressions of which were ≥1.5-fold changed (16 up-regulated) in the striatum of 3-NP-treated rats. Immunoprecipitation assay showed decreased binding of Pfn2 with β-actin, the level of which remained unaffected in the striata and cortices of 3-NP-treated rats. Primary cultures of striatal glutamic acid decarboxylase-65/67 immunopositive GABAergic neurons revealed loss of co-existence of Pfn2 and β-actin in fluorescence imaging studies following 3-NP treatment for 24. h. Since Pfn2 is known to regulate dendritic spine dynamics by interacting with β-actin, the reduction in its binding affinity to Pfn2 following 3-NP neurotoxic insult, and the accompanying aberrations of the dendritic spine structure and loss of spine density in striatal neurons suggest that Pfn2 may be involved in neurodegeneration in 3-NP-treated rat model of HD.

Original languageEnglish
Pages (from-to)216-228
Number of pages13
JournalNeuroscience
Volume281
DOIs
StatePublished - Dec 5 2014

Bibliographical note

Publisher Copyright:
© 2014 IBRO.

Funding

J.C., M.P., A.T.A., and M.V. were recipients of Research Fellowships from the Council of Scientific and Industrial Research (CSIR), Govt. of India. S.C.S. received fellowship from the University Grants Commission, and in part from Manovikas Kendra. We acknowledge the financial support from Department of Science and Technology , Govt. of India vide Grant No. SR/FTP/LS-A-61/2001 to UR. A significant part of the study is supported by ‘ Neurodegenerative diseases: Causes and corrections ’ (miND; Grant # BSC-0115 ), funded by the CSIR as a Network Project under 12th Five Year Plan of the Govt. of India.

FundersFunder number
University Grants Commission
Bangladesh Council of Scientific and Industrial Research
Department of Science and Technology, Government of KeralaBSC-0115

    Keywords

    • Dendritic spine density
    • Medium spiny neurons
    • Striatal neurodegeneration
    • Suppression subtractive hybridization
    • Synaptic phenotype
    • β-actin polymerization

    ASJC Scopus subject areas

    • General Neuroscience

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