Region- and Neurotransmitter-dependent Species and Strain Differences in DSP–4–induced Monoamine Depletion in Rodents

Fornai, Francesco; Bassi, L; Torracca, Maria Tilde; Alessandrı̀, Maria Grazia; Scalori, V.; Corsini, Giovanni

doi:10.1006/neur.1996.0032

Cited by 67 publications

(74 citation statements)

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“…These data were recently confirmed by direct catecholamine assay, in situ voltammetry, stimulations of the median forebrain bundle and various pharmacological manipulations [49]. The origin of these fibers is only partly attributed to LC, although this issue remains under debate [25]. …”

Section: Anatomical Connections Of Lc Ne Neurons (Fig 1)mentioning

confidence: 81%

“…In fact, monoamine axons with smaller beaded varicosities have a lower threshold to various neurotoxic insults and are more prone to neurodegeneration compared with the ones bearing large varicosities [25-27]. These considerations call for more in-depth studies aimed at relating the cell biology of synaptic varicosities with selective neuronal vulnerability occurring during neurotoxic insults and neurodegenerative disorders.…”

Section: The Chemical Neuroanatomy Of Ne-containing Lc Neuronsmentioning

confidence: 99%

“…The striatum just has a small amount of NE, receiving only scattered fibers from the LC. Nonetheless, these striatal afferents seem to possess a high turnover rate [25, 26, 37]. …”

Section: Anatomical Connections Of Lc Ne Neurons (Fig 1)mentioning

confidence: 99%

“…While anatomical evidence remains unclear, the presence of NE in the dorsal striatum is widely established, as well as high NE turnover, as witnessed by the high ratio between 3-methoxy4-hydroxyphenylglycol (a major metabolite of NE) and NE in the striatum itself (see for instance [25, 26, 60]). This might explain why damage to LC decreases striatal DA release [25, 26, 61-65].…”

Section: The Anatomy Of Ne-da Interactionsmentioning

confidence: 99%

“…This might explain why damage to LC decreases striatal DA release [25, 26, 61-65]. The anatomical connections between LC NE neurons and DA areas is critical to understanding the behavioural effects induced by methamphetamine (METH).…”

Section: The Anatomy Of Ne-da Interactionsmentioning

confidence: 99%

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The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Ferrucci

Giorgi

Bartalucci

et al. 2013

Current Neuropharmacology

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The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.

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Section: Anatomical Connections Of Lc Ne Neurons (Fig 1)mentioning

confidence: 81%

Section: The Chemical Neuroanatomy Of Ne-containing Lc Neuronsmentioning

confidence: 99%

“…The striatum just has a small amount of NE, receiving only scattered fibers from the LC. Nonetheless, these striatal afferents seem to possess a high turnover rate [25, 26, 37]. …”

Section: Anatomical Connections Of Lc Ne Neurons (Fig 1)mentioning

confidence: 99%

Section: The Anatomy Of Ne-da Interactionsmentioning

confidence: 99%

Section: The Anatomy Of Ne-da Interactionsmentioning

confidence: 99%

See 3 more Smart Citations

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Ferrucci

Giorgi

Bartalucci

et al. 2013

Current Neuropharmacology

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Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice

Fornai

Giorgi

Gesi

et al. 2001

Synapse

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A novel role of microglial NADPH oxidase in mediating extra‐synaptic function of norepinephrine in regulating brain immune homeostasis

Jiang

Chen

Chu

et al. 2015

Glia

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Although the peripheral anti-inflammatory effect of norepinephrine (NE) is well-documented, the mechanism by which this neurotransmitter functions as an anti-inflammatory/neuroprotective agent in the central nervous system is unclear. This study aimed to determine the anti-inflammatory/neuroprotective effects and underlying mechanisms of NE in inflammation-based dopaminergic neurotoxicity models. In mice, NE-depleting toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected at 6 months of lipopolysaccharide (LPS)-induced neuroinflammation. We found that NE depletion enhanced LPS-induced dopaminergic neuron loss in the substantia nigra. This piece of in vivo data prompted us to conduct a series of studies in an effort to elucidate the mechanism as to how NE affects dopamine neuron survival by using primary midbrain neuron-glia cultures. Results showed that sub-micromolar concentrations of NE dose-dependently protected dopaminergic neurons from LPS-induced neurotoxicity by inhibiting microglia activation and subsequent release of pro-inflammatory factors. However, NE-elicited neuroprotection was not totally abolished in cultures from β2-adrenergic receptor (β2-AR) deficient mice, suggesting that novel pathways other than β2-AR are involved. To this end, we found that sub-micromolar NE dose-dependently inhibited NADPH oxidase (NOX2)-generated superoxide, which contributes to the anti-inflammatory and neuroprotective effects of NE. This novel mechanism was indeed adrenergic receptors independent since both (+) and (−) optic isomers of NE displayed the same potency. We further demonstrated that NE inhibited LPS-induced NOX2 activation by blocking the translocation of its cytosolic subunit to plasma membranes. In summary, we revealed a potential physiological role of NE in maintaining brain immune homeostasis and protecting neurons via a novel mechanism.

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Region- and Neurotransmitter-dependent Species and Strain Differences in DSP–4–induced Monoamine Depletion in Rodents

Cited by 67 publications

References 0 publications

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice

A novel role of microglial NADPH oxidase in mediating extra‐synaptic function of norepinephrine in regulating brain immune homeostasis

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