Faculty

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Michael Jakowec, PhD
Associate Professor of Research Neurology
Neurology
MCA 243 Health Sciences Campus Los Angeles
+1 323 442 1057

Overview

The primary focus of research in Dr. Jakowec's laboratory is to better understand the molecular mechanisms involved in neuroplasticity in the injured brain with the emphasis on the basal ganglia, a region of the brain responsible for motor behavior. Currently, his laboratory is exploring the interactions between the neurotransmitter systems involving dopamine, glutamate and serotonine and finding ways to manipulate them to enhance motor behavior. To achieve this goal, animal models of basal gagnglia injury using the neurotoxicant MPTP are being used to investigate intrinsic neuroplasticity as well as using both pharmacological and behavioral modification including intensive treadmill exercise to alter the course of response to injury. Techniques and approaches used in the lab to examine alterations in genes and proteins of interest include immunocytochemistry, in situ hybridization histochemistry, western immunoblotting, light microscopy, gene array, protein profiling, neurochemistry, electrophysiology (with John Walsh), PET imaging (with Giselle Petzinger), blood flow studies (with Daniel Holschneider), immune analysis (with Brett Lund), and behavior (with Ruth Wood). A major goal of these studies is to translate their findings to develop new therapeutic treatments for Parkinson's disease and to possibly alter disease progression and demonstrated in our recent publication (Fisher et al, 2008)

Publications

Wang Z, Stefanko DP, Guo Y, Toy WA, Petzinger GM, Jakowec MW, Holschneider DP. Evidence of functional brain reorganization on the basis of blood flow changes in the CAG140 knock-in mouse model of Huntington's disease. Neuroreport. 2016 Jun 15; 27(9):632-9. View in: PubMed

Toy WA, Petzinger GM, Leyshon BJ, Akopian GK, Walsh JP, Hoffman MV, Vuckovic MG, Jakowec MW. 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. 2014 Mar; 63:201-9. View in: PubMed

Franklin KM, Asatryan L, Jakowec MW, Trudell JR, Bell RL, Davies DL. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. Front Neurosci. 2014; 8:176. View in: PubMed

Kintz N, Petzinger GM, Akopian G, Ptasnik S, Williams C, Jakowec MW, Walsh JP. Exercise modifies a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor expression in striatopallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse. J Neurosci Res. 2013 Nov; 91(11):1492-507. View in: PubMed

Wyatt LR, Godar SC, Khoja S, Jakowec MW, Alkana RL, Bortolato M, Davies DL. Sociocommunicative and sensorimotor impairments in male P2X4-deficient mice. Neuropsychopharmacology. 2013 Sep; 38(10):1993-2002. View in: PubMed

Fisher BE, Li Q, Nacca A, Salem GJ, Song J, Yip J, Hui JS, Jakowec MW, Petzinger GM. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson's disease. Neuroreport. 2013 Jul 10; 24(10):509-14. View in: PubMed

Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease. Lancet Neurol. 2013 Jul; 12(7):716-26. View in: PubMed

Wood RI, Armstrong A, Fridkin V, Shah V, Najafi A, Jakowec M. 'Roid rage in rats? Testosterone effects on aggressive motivation, impulsivity and tyrosine hydroxylase. Physiol Behav. 2013 Feb 17; 110-111:6-12. View in: PubMed

Beeler JA, Petzinger G, Jakowec MW. The Enemy within: Propagation of Aberrant Corticostriatal Learning to Cortical Function in Parkinson's Disease. Front Neurol. 2013; 4:134. View in: PubMed

Wang Z, Myers KG, Guo Y, Ocampo MA, Pang RD, Jakowec MW, Holschneider DP. Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism. PLoS One. 2013; 8(11):e80058. View in: PubMed

Akopian G, Crawford C, Petzinger G, Jakowec MW, Walsh JP. Brief mitochondrial inhibition causes lasting changes in motor behavior and corticostriatal synaptic physiology in the Fischer 344 rat. Neuroscience. 2012 Jul 26; 215:149-59. View in: PubMed

Crawford CA, Akopian G, Ring J, Jakowec MW, Petzinger GM, Andersen JK, Vittozzi-Wong P, Wang K, Farley CM, Charntikov S, Mitroi D, Beal MF, Chow R, Walsh JP. Acute and long-term response of dopamine nigrostriatal synapses to a single, low-dose episode of 3-nitropropionic acid-mediated chemical hypoxia. Synapse. 2011 Apr; 65(4):339-50. View in: PubMed

Antzoulatos E, Jakowec MW, Petzinger GM, Wood RI. MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse. Parkinsons Dis. 2011; 2011:138471. View in: PubMed

Vuckovic MG, Li Q, Fisher B, Nacca A, Leahy RM, Walsh JP, Mukherjee J, Williams C, Jakowec MW, Petzinger GM. Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: in vivo imaging with [¹8F]fallypride. Mov Disord. 2010 Dec 15; 25(16):2777-84. View in: PubMed

Gorton LM, Vuckovic MG, Vertelkina N, Petzinger GM, Jakowec MW, Wood RI. Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse. Behav Brain Res. 2010 Dec 1; 213(2):253-62. View in: PubMed

Antzoulatos E, Jakowec MW, Petzinger GM, Wood RI. Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease. Pharmacol Biochem Behav. 2010 Jun; 95(4):466-72. View in: PubMed

VanLeeuwen JE, Petzinger GM, Walsh JP, Akopian GK, Vuckovic M, Jakowec MW. Altered AMPA receptor expression with treadmill exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. J Neurosci Res. 2010 Feb 15; 88(3):650-68. View in: PubMed

Petzinger GM, Fisher BE, Van Leeuwen JE, Vukovic M, Akopian G, Meshul CK, Holschneider DP, Nacca A, Walsh JP, Jakowec MW. Enhancing neuroplasticity in the basal ganglia: the role of exercise in Parkinson's disease. Mov Disord. 2010; 25 Suppl 1:S141-5. View in: PubMed

Vuckovic MG, Wood RI, Holschneider DP, Abernathy A, Togasaki DM, Smith A, Petzinger GM, Jakowec MW. Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. Neurobiol Dis. 2008 Nov; 32(2):319-27. View in: PubMed

Akopian G, Crawford C, Beal MF, Cappelletti M, Jakowec MW, Petzinger GM, Zheng L, Gheorghe SL, Reichel CM, Chow R, Walsh JP. Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 h after 3-nitropropionic-acid-induced chemical hypoxia. J Neurosci. 2008 Sep 17; 28(38):9585-97. View in: PubMed

Fisher BE, Wu AD, Salem GJ, Song J, Lin CH, Yip J, Cen S, Gordon J, Jakowec M, Petzinger G. The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson's disease. Arch Phys Med Rehabil. 2008 Jul; 89(7):1221-9. View in: PubMed

Petzinger GM, Walsh JP, Akopian G, Hogg E, Abernathy A, Arevalo P, Turnquist P, Vuckovic M, Fisher BE, Togasaki DM, Jakowec MW. Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. J Neurosci. 2007 May 16; 27(20):5291-300. View in: PubMed

Lund BT, Chakryan Y, Ashikian N, Mnatsakanyan L, Bevan CJ, Aguilera R, Gallaher T, Jakowec MW. Association of MBP peptides with Hsp70 in normal appearing human white matter. J Neurol Sci. 2006 Nov 15; 249(2):122-34. View in: PubMed

Petzinger GM, Fisher B, Hogg E, Abernathy A, Arevalo P, Nixon K, Jakowec MW. Behavioral motor recovery in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned squirrel monkey (Saimiri sciureus): changes in striatal dopamine and expression of tyrosine hydroxylase and dopamine transporter proteins. J Neurosci Res. 2006 Feb 1; 83(2):332-47. View in: PubMed

Shakil SS, Holmer HK, Moore C, Abernathy AT, Jakowec MW, Petzinger GM, Meshul CK. High and low responders to novelty show differential effects in striatal glutamate. Synapse. 2005 Dec 1; 58(3):200-7. View in: PubMed

Hughes-Davis EJ, Cogen JP, Jakowec MW, Cheng HW, Grenningloh G, Meshul CK, McNeill TH. Differential regulation of the growth-associated proteins GAP-43 and superior cervical ganglion 10 in response to lesions of the cortex and substantia nigra in the adult rat. Neuroscience. 2005; 135(4):1231-9. View in: PubMed

Jakowec MW, Petzinger GM. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned model of parkinson's disease, with emphasis on mice and nonhuman primates. Comp Med. 2004 Oct; 54(5):497-513. View in: PubMed

Fisher BE, Petzinger GM, Nixon K, Hogg E, Bremmer S, Meshul CK, Jakowec MW. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia. J Neurosci Res. 2004 Aug 1; 77(3):378-90. View in: PubMed

Jakowec MW, Nixon K, Hogg E, McNeill T, Petzinger GM. Tyrosine hydroxylase and dopamine transporter expression following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration of the mouse nigrostriatal pathway. J Neurosci Res. 2004 May 15; 76(4):539-50. View in: PubMed

Liker MA, Petzinger GM, Nixon K, McNeill T, Jakowec MW. Human neural stem cell transplantation in the MPTP-lesioned mouse. Brain Res. 2003 May 9; 971(2):168-77. View in: PubMed

Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M. The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem. 2001 Mar; 76(5):1265-74. View in: PubMed

Petzinger GM, Quik M, Ivashina E, Jakowec MW, Jakubiak M, Di Monte D, Langston JW. Reliability and validity of a new global dyskinesia rating scale in the MPTP-lesioned non-human primate. Mov Disord. 2001 Mar; 16(2):202-7. View in: PubMed

Jakowec MW, Donaldson DM, Barba J, Petzinger GM. Postnatal expression of alpha-synuclein protein in the rodent substantia nigra and striatum. Dev Neurosci. 2001; 23(2):91-9. View in: PubMed

Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol. 2000 Sep 11; 425(1):58-69. View in: PubMed

Kahle PJ, Jakowec M, Teipel SJ, Hampel H, Petzinger GM, Di Monte DA, Silverberg GD, Möller HJ, Yesavage JA, Tinklenberg JR, Shooter EM, Murphy GM. Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF. Neurology. 2000 Apr 11; 54(7):1498-504. View in: PubMed

Langston JW, Quik M, Petzinger G, Jakowec M, Di Monte DA. Investigating levodopa-induced dyskinesias in the parkinsonian primate. Ann Neurol. 2000 Apr; 47(4 Suppl 1):S79-89. View in: PubMed

Vila M, Vukosavic S, Jackson-Lewis V, Neystat M, Jakowec M, Przedborski S. Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP. J Neurochem. 2000 Feb; 74(2):721-9. View in: PubMed

Tolwani RJ, Jakowec MW, Petzinger GM, Green S, Waggie K. Experimental models of Parkinson's disease: insights from many models. Lab Anim Sci. 1999 Aug; 49(4):363-71. View in: PubMed

Jakowec MW, Petzinger GM, Sastry S, Donaldson DM, McCormack A, Langston JW. The native form of alpha-synuclein is not found in the cerebrospinal fluid of patients with Parkinson's disease or normal controls. Neurosci Lett. 1998 Aug 28; 253(1):13-6. View in: PubMed

Jakowec MW, Jackson-Lewis V, Chen X, Langston JW, Przedborski S. The postnatal development of AMPA receptor subunits in the basal ganglia of the rat. Dev Neurosci. 1998; 20(1):19-33. View in: PubMed

Di Monte DA, DeLanney LE, Irwin I, Royland JE, Chan P, Jakowec MW, Langston JW. Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of L-DOPA-treated monkeys. Brain Res. 1996 Oct 28; 738(1):53-9. View in: PubMed

Przedborski S, Donaldson D, Jakowec M, Kish SJ, Guttman M, Rosoklija G, Hays AP. Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis. Ann Neurol. 1996 Feb; 39(2):158-65. View in: PubMed

Jackson-Lewis V, Jakowec M, Burke RE, Przedborski S. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration. 1995 Sep; 4(3):257-69. View in: PubMed

Jakowec MW, Fox AJ, Martin LJ, Kalb RG. Quantitative and qualitative changes in AMPA receptor expression during spinal cord development. Neuroscience. 1995 Aug; 67(4):893-907. View in: PubMed

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