Rodent Models and Contemporary Molecular Techniques: Notable Feats yet Incomplete Explanations of Parkinson’ s Disease Pathogenesis Sharawan Yadav & Anubhuti Dixit & Sonal Agrawal & Ashish Singh & Garima Srivastava & Anand Kumar Singh & Pramod Kumar Srivastava & Om Prakash & Mahendra Pratap Singh Received: 14 May 2012 / Accepted: 13 June 2012 / Published online: 27 June 2012 # Springer Science+Business Media, LLC 2012 Abstract Rodent models and molecular tools, mainly omics and RNA interference, have been rigorously used to decode the intangible etiology and pathogenesis of Parkin- son’ s disease (PD). Although convention of contemporary molecular techniques and multiple rodent models paved imperative leads in deciphering the role of putative causa- tive factors and sequential events leading to PD, complete and clear-cut mechanisms of pathogenesis are still hard to pin down. The current article reviews the implications and pros and cons of rodent models and molecular tools in understanding the molecular and cellular bases of PD path- ogenesis based on the existing literature. Probable rationales for short of comprehensive leads and future possibilities in spite of the extensive applications of molecular tools and rodent models have also been discussed. Keywords Parkinson’ s disease . Rodent models . Genomics . Transcriptomics . Proteomics . RNA interference Introduction James Parkinson offered the first landmark portrayal on shaking palsy; however, the name Parkinson’s disease (PD) was given by Jean-Martin Charcot [1, 2]. PD is recognized as the most common progressive, baffling, and devastating neurodegenerative disorder in the elderly after the Alzheimer disease [3, 4]. This movement disorder is distinguished by the selective degeneration of the nigros- triatal dopaminergic neurons, accumulation of cytoplasmic protein aggregates and onset of phenotypic features, such as resting tremor, rigidity and bradykinesia, etc., leading to loss of control over the movement [3–6]. The degeneration of selective neurons is accountable for the decreased dopamine level in the striatum that ultimately results in the clinical manifestations [6]. Although an early diagnosis is dreadfully difficult, physical and clinical examinations and sympto- matic features are used to diagnose the patients after consid- erable dopaminergic neurodegeneration and manifestation of noticeable complications [7]. Moreover, the comprehensive explanations of pathogenesis and permanent cure are not yet established, and therapeutic and surgical procedures offer provisional aids [7, 8]. One of the most commonly accepted notions for the onset of symptomatic features of PD is the resultant interplay of the environmental factors, increased age, and genetic sus- ceptibility of an individual [3, 5, 9]. Administration of 6- hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), reserpine, methamphetamine, rotenone, maneb, zinc, manganese, paraquat, and cyper- methrin in rodents develop many symptomatic features mimicking PD [9–14]. These chemicals either alone or in combination inhibit mitochondrial function resulting in depleted energy metabolism, free radical generation, and neuroinflammation leading to programmed cell death and selective neurodegeneration [15–19]. Some environmentally relevant chemicals directly cross the blood–brain barrier (BBB) and enter the brain owing to their lipophilic nature, such as MPTP and rotenone. Others, those are hydrophilic in Authors Sharawan Yadav and Anubhuti Dixit contributed equally to this work. S. Yadav : A. Dixit : S. Agrawal : A. Singh : G. Srivastava : A. K. Singh : M. P. Singh (*) CSIR-Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Post Box 80, Lucknow - 226 001, Uttar Pradesh, India e-mail: singhmahendrapratap@rediffmail.com P. K. Srivastava : O. Prakash Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh, India Mol Neurobiol (2012) 46:495–512 DOI 10.1007/s12035-012-8291-8