John Elsworth, PhD
Research & Publications
Biography
News
Research Summary
Dysfunction of brain dopamine neurons is critically involved in the pathology of several neurologic and psychiatric disorders. Dr Elsworth’s research focuses on the “development, dysfunction, and demise” of dopamine neurons. The goal is to understand the mechanisms underlying the particular susceptibility of dopamine neurons to damage, and devising strategies for protecting, repairing or replacing these cells.
Specialized Terms: Dopamine neurons; Oxidative stress; Mitochondrial dysfunction; Uncoupling proteins; Neurotrophic factors; Development; Stem cell transplantation; Parkinson’s disease; Striatum; Prefrontal cortex; Schizophrenia.
Extensive Research Description
Dysfunction of dopamine neurons is implicated in several psychiatric or neurological disorders, notably Parkinson’s disease and schizophrenia. During the prenatal period the fetal brain undergoes dramatic changes, as structures and connections form according to strict spatial and temporal criteria. It follows then that during development environmental insults have greater potential to exert profound and permanent changes than other times during life and may affect the risk of the offspring succumbing to CNS disorders. A major focus of investigations is our finding of varying susceptibility of primate dopamine neurons to damage at different periods of development. Our research has identified prenatal phases when primate DA neurons are especially vulnerable to oxidative stress or endocrine disruptors and other times during development when they are remarkably resistant to such damage. These models offer insight into biochemical factors that may contribute to dopamine-dependent disorders later in life, and also provide novel strategies and mechanisms for protecting and preserving adult dopamine neurons.
Another field of research is investigation of the regulation of dopamine neurons innervating the prefrontal cortex, as our research has indicated that this input appears to regulate changes in dendrites and synapses, which are critical to the executive functions of this brain region. Experimental restoration of normal dopamine transmission in the prefrontal cortex would enable treatment of cognitive deficits that are characteristic of Parkinson’s disease and schizophrenia.
Other research is focused on repair of the damaged nigrostriatal dopamine system, using strategies such as implants of modified stem cells and neurotrophic factor gene therapy, with direct relevance to the treatment of Parkinson’s disease.
Coauthors
Research Interests
Dopamine; Mitochondria; Parkinson Disease; Schizophrenia; Prefrontal Cortex; Oxidative Stress; Stem Cell Transplantation
Selected Publications
- Primate phencyclidine model of schizophrenia: sex-specific effects on cognition, brain derived neurotrophic factor, spine synapses, and dopamine turnover in prefrontal cortex.Elsworth JD, Groman SM, Jentsch JD, Leranth C, Redmond DE, Kim JD, Diano S, Roth RH. Primate phencyclidine model of schizophrenia: sex-specific effects on cognition, brain derived neurotrophic factor, spine synapses, and dopamine turnover in prefrontal cortex. The International Journal Of Neuropsychopharmacology / Official Scientific Journal Of The Collegium Internationale Neuropsychopharmacologicum (CINP) 2014, 18.
- Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys.Elsworth JD, Jentsch JD, Groman SM, Roth RH, Redmond ED, Leranth C. Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys. The Journal Of Comparative Neurology 2015, 523:1248-57.
- Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates.Elsworth JD, Jentsch JD, Vandevoort CA, Roth RH, Jr DE, Leranth C. Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates. Neurotoxicology 2013, 35:113-20.
- Loss of asymmetric spine synapses in prefrontal cortex of motor-asymptomatic, dopamine-depleted, cognitively impaired MPTP-treated monkeys.Elsworth JD, Leranth C, Redmond DE, Roth RH. Loss of asymmetric spine synapses in prefrontal cortex of motor-asymptomatic, dopamine-depleted, cognitively impaired MPTP-treated monkeys. The International Journal Of Neuropsychopharmacology / Official Scientific Journal Of The Collegium Internationale Neuropsychopharmacologicum (CINP) 2013, 16:905-12.
- Coordinated expression of dopamine transporter and vesicular monoamine transporter in the primate striatum during development.Elsworth JD, Redmond DE, Roth RH. Coordinated expression of dopamine transporter and vesicular monoamine transporter in the primate striatum during development. Synapse (New York, N.Y.) 2013, 67:580-5.
- Susceptibility to a parkinsonian toxin varies during primate development.Morrow BA, Roth RH, Redmond DE, Diano S, Elsworth JD. Susceptibility to a parkinsonian toxin varies during primate development. Experimental Neurology 2012, 235:273-81.
- Asenapine effects on cognitive and monoamine dysfunction elicited by subchronic phencyclidine administration.Elsworth JD, Groman SM, Jentsch JD, Valles R, Shahid M, Wong E, Marston H, Roth RH. Asenapine effects on cognitive and monoamine dysfunction elicited by subchronic phencyclidine administration. Neuropharmacology 2012, 62:1442-52.
- Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson's disease.Morrow BA, Roth RH, Redmond DE, Elsworth JD. Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson's disease. Neuroscience 2011, 189:277-85.
- Phencyclidine-induced loss of asymmetric spine synapses in rodent prefrontal cortex is reversed by acute and chronic treatment with olanzapine.Elsworth JD, Morrow BA, Hajszan T, Leranth C, Roth RH. Phencyclidine-induced loss of asymmetric spine synapses in rodent prefrontal cortex is reversed by acute and chronic treatment with olanzapine. Neuropsychopharmacology : Official Publication Of The American College Of Neuropsychopharmacology 2011, 36:2054-61.
- Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys.Elsworth JD, Hajszan T, Leranth C, Roth RH. Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys. The International Journal Of Neuropsychopharmacology / Official Scientific Journal Of The Collegium Internationale Neuropsychopharmacologicum (CINP) 2011, 14:1411-5.
- GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function.Horvath TL, Erion DM, Elsworth JD, Roth RH, Shulman GI, Andrews ZB. GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function. Neurobiology Of Disease 2011, 43:152-62.