title: Profilin-2 increased expression and its altered interaction with β-actin in the striatum of 3-nitropropionic acid-induced Huntington's disease in rats.
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 24h. 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.
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India.
authors.forename: J
authors.initials: J
authors.lastname: Chakraborty
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India; Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Plot I-24, Sector-J, E.M. Bypass, Kolkata 700 107, India. Electronic address: pandeym2@niddk.nih.gov.
authors.forename: M
authors.initials: M
authors.lastname: Pandey
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India. Electronic address: nammalkaidery@gru.edu.
authors.forename: A K
authors.initials: AK
authors.lastname: Navneet
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India. Electronic address: ambili.thoppuvalappil@florey.edu.au.
authors.forename: T A
authors.initials: TA
authors.lastname: Appukuttan
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India. Electronic address: m.varghese@rediffmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Varghese
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India; Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Plot I-24, Sector-J, E.M. Bypass, Kolkata 700 107, India. Electronic address: sreetama.senchandra@cnmc.org.
authors.forename: S C
authors.initials: SC
authors.lastname: Sreetama
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Plot I-24, Sector-J, E.M. Bypass, Kolkata 700 107, India. Electronic address: ushamvk@yahoo.co.in.
authors.forename: U
authors.initials: U
authors.lastname: Rajamma
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Division of Cell Biology & Physiology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India. Electronic address: mohankumar@iicb.res.in.
authors.forename: K P
authors.initials: KP
authors.lastname: Mohanakumar
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003292:Convulsants / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009574:Nitro Compounds / Q000494:pharmacology; D051304:Profilins / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D003292:Convulsants; D009574:Nitro Compounds; C495743:Pfn2 protein, rat; D051304:Profilins; D011422:Propionates; C015392:3-nitropropionic acid
keywords: dendritic spine density; medium spiny neurons; striatal neurodegeneration; suppression subtractive hybridization; synaptic phenotype; β-actin polymerization