Dose‐related neuroprotective effects of chronic nicotine in 6‐hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice

Ryan, Rebecca; Ross, Shelley; Drago, John; Loiacono, Richard

doi:10.1038/sj.bjp.0703989

Cited by 176 publications

(155 citation statements)

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“…Other autoradiography studies of rats have demonstrated that chronic administration of nicotine increases glucose transporter (Glut1 and Glut3) densities in an array of brain areas (Duelli et al, 1998) and that chronically administered low dose nicotine is protective against neurodegenerative agents in the striatum (a model for Parkinson's Disease) (Ryan et al, 2001). …”

Section: Glutamatergic (And Other) Effects Of Nicotine/cigarette Smokingmentioning

confidence: 99%

Functional brain imaging of tobacco use and dependence

Brody

2006

Journal of Psychiatric Research

176

136

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While most cigarette smokers endorse a desire to quit smoking, only about 14% to 49% will achieve abstinence after 6 months or more of treatment. A greater understanding of the effects of smoking on brain function may (in conjunction with other lines of research) result in improved pharmacological (and behavioral) interventions. Many research groups have examined the effects of acute and chronic nicotine/cigarette exposure on brain activity using functional imaging; the purpose of this paper is to synthesize findings from such studies and present a coherent model of brain function in smokers. Responses to acute administration of nicotine/smoking include: a reduction in global brain activity; activation of the prefrontal cortex, thalamus, and visual system; activation of the thalamus and visual cortex during visual cognitive tasks; and increased dopamine (DA) concentration in the ventral striatum/nucleus accumbens. Responses to chronic nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B activity in the basal ganglia and a reduction in α 4 β 2 nicotinic acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken together, these findings indicate that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs, indirect stimulation via DA release or MAO inhibition, or a combination of these factors. Activation of this circuitry may be responsible for the effects of smoking seen in tobacco dependent subjects, such as improvements in attentional performance, mood, anxiety, and irritability.

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Section: Glutamatergic (And Other) Effects Of Nicotine/cigarette Smokingmentioning

confidence: 99%

Functional brain imaging of tobacco use and dependence

Brody

2006

Journal of Psychiatric Research

176

136

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Section: Nicotine-mediated Protection Against Toxic Insults In Experimentioning

confidence: 99%

“…In rats, nicotine pre-treatment protects against nigrostriatal degeneration induced by the dopaminergic neurotoxin 6-hydroxydopamine or by mechanical lesions [23][24][25][26][27][28]. A neuroprotective effect of nicotine is also observed in striatum of mice in which nigrostriatal damage is induced by the selective dopaminergic neurotoxin MPTP [24,[29][30][31][32][33][34][35][36][37][38][39].…”

Section: Nicotine-mediated Protection Against Toxic Insults In Experimentioning

confidence: 99%

“…Although the nature of this variability is uncertain, it may be due to the relatively large lesion generated with MPTP. This possibility stems from findings that neuroprotection is observed in mice treated with methamphetamine and paraquat, both of which result in milder damage to the nigrostriatal dopaminergic system [24,40].Nicotine-induced protection against striatal damage is also observed in MPTP-treated nonhuman primates, a model that may more closely resemble the human disease [41][42][43]. A chronic nicotine treatment regimen improved a variety of neurochemical markers in MPTPlesioned nicotine treated animals, including tyrosine hydroxylase, the dopamine and vesicular monoamine transporters, dopamine levels and nAChR expression [42,43].…”

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confidence: 99%

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Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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“…Although there are numerous studies that suggest that nicotine may play a role in neuroprotection (Ryan et al, 2001;Guan et al, 2003;Stevens et al, 2003), prenatal nicotine exposure has been shown to have deleterious effects on the neonate's ability to respond to hypoxic challenges. Fewell et al (2001) found that offspring exposed to a prenatal nicotine dose of 6 mg/kg/day, resulting in a plasma nicotine concentration of 3578 ng/ ml, had a decreased ability to auto resuscitate after repeated exposure to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia

et al. 2005

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BACKGROUND: Neonatal neurodevelopment is influenced by a variety of external factors, although the mechanisms responsible are poorly understood. Prenatal hypoxia, from physiological or chemical sources, can have no discernible effect, or can result in a broad spectrum of abnormalities. METHODS: To mimic some of the maternal effects of smoking, we developed a model that investigates the effects of intermittent hypoxia (IH), with or without concurrent nicotine in timed pregnant Sprague-Dawley rats. RESULTS: We found no significant differences between litter sizes or birthweight of pups from any treatment group, but animals exposed to IH (with or without nicotine) showed long term diminished body weights. Animals subjected to IH consistently showed a transient delay in neuronal migration early in the postpartum period, which was amplified by concurrent nicotine administration. We observed increased c-Abl protein levels in animals from the IH treatment groups. Multiple proteins involved in the intricate control of neuronal migration were also altered in response to this treatment, primarily the downstream targets of c-Abl: Cdk5, p25, and the cytoskeletal elements neurofilament H and F-actin and catalase. Catalase activity and protein levels, already elevated in response to IH, were further amplified by simultaneous nicotine exposure. CONCLUSIONS: This new model provides a novel system for investigating the effects of low grade IH in the developing brain and suggests that concurrent nicotine further aggravates many of the deleterious effects of IH. We also describe IH as a previously unreported mechanism for c-Abl expression. Birth Defects Res B 74:287-299, 2005. r 2005 Wiley-Liss, Inc.

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Dose‐related neuroprotective effects of chronic nicotine in 6‐hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice

Cited by 176 publications

References 47 publications

Functional brain imaging of tobacco use and dependence

Functional brain imaging of tobacco use and dependence

Nicotinic receptors as CNS targets for Parkinson's disease

Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia

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