QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 24, 2005, 25(34):7805-7812; doi:10.1523/JNEUROSCI.2038-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (37) Citing Articles via Google Scholar Google Scholar Articles by Schütz, B. Articles by Heneka, M. T. Search for Related Content PubMed PubMed Citation Articles by Schütz, B. Articles by Heneka, M. T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Amyotrophic Lateral Sclerosis

 Previous Article  |  Next Article 

Neurobiology of Disease
The Oral Antidiabetic Pioglitazone Protects from Neurodegeneration and Amyotrophic Lateral Sclerosis-Like Symptoms in Superoxide Dismutase-G93A Transgenic Mice

Burkhard Schütz,¹ Jens Reimann,² Lucia Dumitrescu-Ozimek,² Karin Kappes-Horn,² Gary E. Landreth,³ Britta Schürmann,¹ Andreas Zimmer,¹ and Michael T. Heneka²

¹Laboratory of Molecular Neurobiology, Department of Psychiatry and Psychotherapy, and ²Laboratory of Neuroinflammation, Department of Neurology, University of Bonn, 53127 Bonn, Germany, and ³Alzheimer Research Laboratory, Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106-4928

Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Because accompanying inflammation may interact with and promote neurodegeneration, anti-inflammatory treatment strategies are being evaluated. Because peroxisome proliferator-activated receptor (PPAR) agonists act as potent anti-inflammatory drugs, we tested whether superoxide dismutase (SOD1)-G93A transgenic mice, a mouse model of ALS, benefit from oral treatment with the PPAR agonist pioglitazone (Pio). Pio-treated transgenic mice revealed improved muscle strength and body weight, exhibited a delayed disease onset, and survived significantly longer than nontreated SOD1-G93A mice. Quantification of motor neurons of the spinal cord at day 90 revealed complete neuroprotection by Pio, whereas nontreated SOD1-G93A mice had lost 30% of motor neurons. This was paralleled by preservation of the median fiber diameter of the quadriceps muscle, indicating not only morphological but also functional protection of motor neurons by Pio. Activated microglia were significantly reduced at sites of neurodegeneration in Pio-treated SOD1-G93A mice, as were the protein levels of cyclooxygenase 2 and inducible nitric oxide synthase. Interestingly, mRNA levels of the suppressor of cytokine signaling 1 and 3 genes were increased by Pio, whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected.

Key words: motor neurons; degeneration; neuroinflammation; peroxisome proliferator-activated receptor; microglia; glia

---

Received Jan 16, 2005; revised July 2, 2005; accepted July 5, 2005.

This article has been cited by other articles:

				R. A. Quintanilla, Y. N. Jin, K. Fuenzalida, M. Bronfman, and G. V. W. Johnson Rosiglitazone Treatment Prevents Mitochondrial Dysfunction in Mutant Huntingtin-expressing Cells: POSSIBLE ROLE OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-{gamma} (PPAR{gamma}) IN THE PATHOGENESIS OF HUNTINGTON DISEASE J. Biol. Chem., September 12, 2008; 283(37): 25628 - 25637. [Abstract] [Full Text] [PDF]

				D. J. Gifondorwa, M. B. Robinson, C. D. Hayes, A. R. Taylor, D. M. Prevette, R. W. Oppenheim, J. Caress, and C. E. Milligan Exogenous Delivery of Heat Shock Protein 70 Increases Lifespan in a Mouse Model of Amyotrophic Lateral Sclerosis J. Neurosci., November 28, 2007; 27(48): 13173 - 13180. [Abstract] [Full Text] [PDF]

				X. Hou, R. Liu, S. Ross, E. J. Smart, H. Zhu, and W. Gong Crystallographic Studies of Human MitoNEET J. Biol. Chem., November 16, 2007; 282(46): 33242 - 33246. [Abstract] [Full Text] [PDF]

				P. Fanara, J. Banerjee, R. V. Hueck, M. R. Harper, M. Awada, H. Turner, K. H. Husted, R. Brandt, and M. K. Hellerstein Stabilization of Hyperdynamic Microtubules Is Neuroprotective in Amyotrophic Lateral Sclerosis J. Biol. Chem., August 10, 2007; 282(32): 23465 - 23472. [Abstract] [Full Text] [PDF]

				S.-W. Park, J.-H. Yi, G. Miranpuri, I. Satriotomo, K. Bowen, D. K. Resnick, and R. Vemuganti Thiazolidinedione Class of Peroxisome Proliferator-Activated Receptor {gamma} Agonists Prevents Neuronal Damage, Motor Dysfunction, Myelin Loss, Neuropathic Pain, and Inflammation after Spinal Cord Injury in Adult Rats J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1002 - 1012. [Abstract] [Full Text] [PDF]

				J. Mojsilovic-Petrovic, G.-B. Jeong, A. Crocker, A. Arneja, S. David, D. Russell, and R. G. Kalb Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors J. Neurosci., September 6, 2006; 26(36): 9250 - 9263. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help