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Michael Jakowec, PhD

Professor of Research Neurology

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Phone +1 323 442 1057
Email mjakowec@surgery.usc.edu
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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

  • Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson’s Disease Brain Imaging Behav. 2024 Feb; 18(1):57-65. . View in PubMed
  • A naturally occurring variant of SHLP2 is a protective factor in Parkinson’s disease Mol Psychiatry. 2024 Jan 03. . View in PubMed
  • Exercise alters cortico-basal ganglia network metabolic connectivity: a mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome Brain Struct Funct. 2023 Nov; 228(8):1865-1884. . View in PubMed
  • Physical activity intensity is associated with cognition and functional connectivity in Parkinson’s disease Parkinsonism Relat Disord. 2022 Nov; 104:7-14. . View in PubMed
  • Promoting Physical Activity in a Spanish-Speaking Latina Population of Low Socioeconomic Status With Chronic Neurological Disorders: Proof-of-Concept Study JMIR Form Res. 2022 Apr 20; 6(4):e34312. . View in PubMed
  • Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning Mol Neurobiol. 2022 Feb; 59(2):1002-1017. . View in PubMed
  • Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson’s disease: a pilot and feasibility study Neuroreport. 2022 05 04; 33(7):291-296. . View in PubMed
  • A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model Curr Res Neurobiol. 2022; 3:100039. . View in PubMed
  • Exogenous l-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice J Neurosci Res. 2021 05; 99(5):1433-1447. . View in PubMed
  • Global and Regional Changes in Perivascular Space in Idiopathic and Familial Parkinson’s Disease Mov Disord. 2021 05; 36(5):1126-1136. . View in PubMed
  • Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson’s disease Parkinsonism Relat Disord. 2021 05; 86:19-26. . View in PubMed
  • The Effects of Cardiorespiratory and Motor Skill Fitness on Intrinsic Functional Connectivity of Neural Networks in Individuals with Parkinson’s Disease Brain Plast. 2021; 7(2):77-95. . View in PubMed
  • Cognition and motor learning in a Parkinson’s disease cohort: importance of recall in episodic memory Neuroreport. 2021 10 06; 32(14):1153-1160. . View in PubMed
  • Treadmill exercise rescues mitochondrial function and motor behavior in the CAG140 knock-in mouse model of Huntington’s disease Chem Biol Interact. 2020 Jan 05; 315:108907. . View in PubMed
  • Mild cognitive impairment, psychiatric symptoms, and executive functioning in patients with Parkinson’s disease Int J Geriatr Psychiatry. 2020 04; 35(4):396-404. . View in PubMed
  • Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning Neuroreport. 2020 10 14; 31(15):1055-1064. . View in PubMed
  • The macrocyclic lactones ivermectin and moxidectin show differential effects on rotational behavior in the 6-hydroxydopamine mouse model of Parkinson’s disease Behav Brain Res. 2020 09 01; 393:112804. . View in PubMed
  • Exercise induces region-specific remodeling of astrocyte morphology and reactive astrocyte gene expression patterns in male mice J Neurosci Res. 2019 09; 97(9):1081-1094. . View in PubMed
  • Intensive treadmill exercise increases expression of hypoxia-inducible factor 1a and its downstream transcript targets: a potential role in neuroplasticity Neuroreport. 2019 06 12; 30(9):619-627. . View in PubMed
  • Dopamine Receptor Blockade Attenuates Purinergic P2X4 Receptor-Mediated Prepulse Inhibition Deficits and Underlying Molecular Mechanisms Front Cell Neurosci. 2019; 13:331. . View in PubMed
  • Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders Psychopharmacology (Berl). 2018 06; 235(6):1697-1709. . View in PubMed
  • Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice Alcohol. 2018 05; 68:63-70. . View in PubMed
  • Treadmill exercise modifies dopamine receptor expression in the prefrontal cortex of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson’s disease Neuroreport. 2017 Oct 18; 28(15):987-995. . View in PubMed
  • Treadmill exercise delays the onset of non-motor behaviors and striatal pathology in the CAG140 knock-in mouse model of Huntington’s disease Neurobiol Dis. 2017 Sep; 105:15-32. . View in PubMed
  • The Oxygen Paradox, the French Paradox, and age-related diseases Geroscience. 2017 12; 39(5-6):499-550. . View in PubMed
  • Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder Neuropharmacology. 2017 02; 113(Pt A):60-70. . View in PubMed
  • Engaging cognitive circuits to promote motor recovery in degenerative disordersexercise as a learning modality. J Hum Kinet. 2016 Sep 01; 52:35-51. . View in PubMed
  • Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors J Neurochem. 2016 10; 139(1):134-48. . View in PubMed
  • 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 06 15; 27(9):632-9. . View in PubMed
  • The Effects of Exercise on Dopamine Neurotransmission in Parkinson’s Disease: Targeting Neuroplasticity to Modulate Basal Ganglia Circuitry Brain Plast. 2015; 1(1):29-39. . View in PubMed
  • 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
  • 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
  • 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
  • Sociocommunicative and sensorimotor impairments in male P2X4-deficient mice Neuropsychopharmacology. 2013 Sep; 38(10):1993-2002. . View in PubMed
  • 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
  • Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease Lancet Neurol. 2013 Jul; 12(7):716-26. . View in PubMed
  • Physiol Behav. 2013 Feb 17; 110-111:6-12. . View in PubMed
  • 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
  • The Enemy within: Propagation of Aberrant Corticostriatal Learning to Cortical Function in Parkinson’s Disease Front Neurol. 2013; 4:134. . View in PubMed
  • 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
  • The role of exercise in facilitating basal ganglia function in Parkinson’s disease Neurodegener Dis Manag. 2011 Apr 01; 1(2):157-170. . View in PubMed
  • 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
  • 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
  • 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
  • Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse Behav Brain Res. 2010 Dec 01; 213(2):253-62. . View in PubMed
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 01; 83(2):332-47. . View in PubMed
  • High and low responders to novelty show differential effects in striatal glutamate Synapse. 2005 Dec 01; 58(3):200-7. . View in PubMed
  • 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
  • 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
  • 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 01; 77(3):378-90. . View in PubMed
  • 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
  • Human neural stem cell transplantation in the MPTP-lesioned mouse Brain Res. 2003 May 09; 971(2):168-77. . View in PubMed
  • 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
  • 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
  • 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
  • Combined assessment of tau and neuronal thread protein in Alzheimer’s disease CSF Neurology. 2000 Apr 11; 54(7):1498-504. . View in PubMed
  • Investigating levodopa-induced dyskinesias in the parkinsonian primate Ann Neurol. 2000 Apr; 47(4 Suppl 1):S79-89. . View in PubMed
  • 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
  • Experimental models of Parkinson’s disease: insights from many models Lab Anim Sci. 1999 Aug; 49(4):363-71. . View in PubMed
  • 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
  • The postnatal development of AMPA receptor subunits in the basal ganglia of the rat Dev Neurosci. 1998; 20(1):19-33. . View in PubMed
  • Role of nitric oxide in methamphetamine neurotoxicity: protection by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase J Neurochem. 1996 Dec; 67(6):2443-50. . View in PubMed
  • 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
  • Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis Ann Neurol. 1996 Feb; 39(2):158-65. . View in PubMed
  • 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
  • Quantitative and qualitative changes in AMPA receptor expression during spinal cord development Neuroscience. 1995 Aug; 67(4):893-907. . View in PubMed
  • In situ hybridization analysis of AMPA receptor subunit gene expression in the developing rat spinal cord Neuroscience. 1995 Aug; 67(4):909-20. . View in PubMed
  • Mutational analysis of the open reading frames in the transposable element IS1 Genetics. 1988 Sep; 120(1):47-55. . View in PubMed
  • Expression of proteins essential for IS1 transposition: specific binding of InsA to the ends of IS1 EMBO J. 1987 Oct; 6(10):3163-9. . View in PubMed
  • Recombinant plasmid conferring proline overproduction and osmotic tolerance Appl Environ Microbiol. 1985 Aug; 50(2):441-6. . View in PubMed

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