The neostriatal mosaic: III. Biochemical and developmental dissociation of patch-matrix mesostriatal systems

Gerfen, Charles R.; Baimbridge, K.G.; Thibault, Jean

doi:10.1523/jneurosci.07-12-03935.1987

Cited by 320 publications

(157 citation statements)

References 40 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…This possibility is consistent with previous work indicating that dopaminergic afferents from the nigra to the striatum are variably susceptible to nigrostriatal insults [114,115]. Studies to understand the molecular basis for this enhanced vulnerability have linked calbindin to nigrostriatal dopamine neuron survival [116][117][118] while neuromelanin has been negatively associated [119][120][121][122]. However, a definitive connection of either of these markers with nigrostriatal damage remains to be established.…”

Section: Preferential Loss Of the α6α4β2β3 Nachr Subtype With Nigrostsupporting

confidence: 89%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

View full text Add to dashboard Cite

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...

show abstract

Section: Preferential Loss Of the α6α4β2β3 Nachr Subtype With Nigrostsupporting

confidence: 89%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Nonetheless, the data offer compelling evidence that dorsal tier neurons project to the matrix, and ventral tier neurons project to the patches. Data provided in the following paper (Gerfen et al, 1987), using different methods, supports this conclusion. To summarize those data, neonatal striatal6-OHDA lesions, which selectively destroy the mesostriatal inputs to the naloxone binding of r-opiate receptor-rich patches in adjacent sections.…”

Section: Discussionsupporting

confidence: 59%

The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems

1987

Self Cite

View full text Add to dashboard Cite

Mesostriatal projections, which arise from dopaminergic and non- dopaminergic neurons in the ventral tegmental area, substantia nigra, and retrorubral area, are compartmentally organized in the striatum. Anterograde axonal tract tracing with Phaseolus vulgaris- leucoagglutinin (PHA-L), combined with immunohistochemical localization of tyrosine hydroxylase (TH) and autoradiographic localization of mu- opiate receptor binding sites, shows that midbrain projections to the striatum are distributed to either the mu-opiate receptor-rich “patch” or the receptor-poor “matrix” striatal compartments. Three morphologically distinct mesostriatal afferent fiber types are labeled. The first type, type A, forms a plexus of relatively thin (0.1–0.4 micron), smooth fibers with small varicosities (0.3–0.6 micron). A second type, type B, is similar to the first in forming a plexus of fibers, but is slightly thicker (0.2–0.6 micron), with more frequent varicosities (0.4–1.0 micron) that give this fiber type a crinkled appearance. The third type, type C, constitutes a minority of striatal afferents and is characterized by its large caliber (0.4–0.7 micron) with large bulbous varicosities (1.2–2.0 micron). Projections of the ventral tegmental area (A10 cell group) are primarily dopaminergic type A fibers directed to the matrix of the ventromedial striatum, including the nucleus accumbens. The retrorubral area (A8 cell group) also provides predominantly dopaminergic type A fibers to the striatal matrix, but these are distributed dorsally. The substantia nigra contains a mixed population of neurons that project to the striatum. Some, located in the dorsal tier of the pars compacta (dorsal A9 cell group), provide dopaminergic type A fibers to the striatal matrix. Others, in the ventral tier of the pars compacta (ventral A9 cell group) and in the ventral tier of the pars reticulata (displaced A9 cells), provide dopaminergic type B fibers to the striatal patches. An additional set of substantia nigra neurons that are non-dopaminergic is the source of type C fibers to the striatal matrix. Thus, distinct dorsal and ventral sets of midbrain dopaminergic neurons project, respectively, to striatal matrix and patches, and there is a non- dopaminergic mesostriatal projection to the matrix.

show abstract

“…13 Both the nigral neurons of the nigrosomes and the limbic cortical neurons of layers V and VI (which develop strong, earlier lewy bodies) project exclusively to striosomes. 14,15 The BBB of the striatum is especially fragile, whether to ischemic, osmotic, or other stressors. After unilateral ischemic stress, increased BBB permeability appears in the striatum before any other brain region, both ipsi-and contralaterally.…”

Section: Discussionmentioning

confidence: 99%

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Gray

Woulfe

2015

J Cereb Blood Flow Metab

296

222

View full text Add to dashboard Cite

In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients. The dense innervation of the striatum by PD-affected regions allows for exploitation of this permeability for therapeutic goals. These results are also discussed in the context of the retrograde transsynaptic hypothesis of PD spread. Keywords: α-synuclein; blood-brain barrier; Parkinson's disease; striatum INTRODUCTION Parkinson's disease (PD) is characterized by aggregation of filamentous or oligomerized α-synuclein and degeneration of specific neuronal regions. According to the dual-hit hypothesis of PD pathogenesis, a microbial or toxic pathogen within the gut lumen and the olfactory mucosa represents the pathogenic agent, with subsequent prion-like spread of pathology, first to the dorsal motor nucleus of the vagus and central olfactory areas, respectively, then to higher centers. The connectional anatomy linking the dorsal motor nucleus and olfactory bulb with higher centers such as the substantia nigra is unproven.We have previously proposed that disease could be spread hematogenously. 1 This is conceivable within the paradigm of retrograde (axon terminal to soma) Lewy pathology spread. 2,3 Almost all regions affected in Braak stage 1 have axon terminals outside the blood-brain barrier (BBB). That same BBB, however, protects the higher-order regions, whose axon terminals reside within the central nervous system, from blood-borne substances. Cell-to-cell spread is a potential mechanism to circumvent this protection but the connectional neuroanatomy is not consistent with the temporal order of Lewy pathology development as it is currently understood.Nigrostriatal dopaminergic neuronal cell bodies develop significant Lewy pathology, but recent studies strongly suggest that α-synuclein aggregation in these cells begins at presynaptic axon terminal in the striatum and spreads retrogradely to nigral

show abstract

The neostriatal mosaic: III. Biochemical and developmental dissociation of patch-matrix mesostriatal systems

Cited by 320 publications

References 40 publications

Nicotinic receptors as CNS targets for Parkinson's disease

Nicotinic receptors as CNS targets for Parkinson's disease

The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Contact Info

Product

Resources

About