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

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

Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder. Neuropharmacology. 2017 Feb; 113(Pt A):60-70. View in: PubMed

Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors. J Neurochem. 2016 Oct; 139(1):134-48. View in: PubMed

Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality. J Hum Kinet. 2016 Sep 01; 52:35-51. 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 Jun 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

'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

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

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

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

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

Postnatal expression of alpha-synuclein protein in the rodent substantia nigra and striatum. Dev Neurosci. 2001; 23(2):91-9. 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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