Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem Parkinsonian brains

Sivam, Subbiah P.

doi:10.1016/0143-4179(91)90148-c

Cited by 51 publications

(27 citation statements)

References 32 publications

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“…In the post mortem PD striatum, Met-Enk and Leu-Enk peptide levels were decreased and DynA (1-8; 1-13 and/or [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] peptide levels remained unchanged, however the presence or severity of LID was not reported in these early studies (14 -16). In addition, clinical and preclinical studies of the effects of opioid antagonists on LID have often displayed conflicting results (11).…”

mentioning

confidence: 93%

“…ϩ : m/z 2147.2 corresponding to DynA (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and m/z 1602.9 (DynA 1-13). The C-terminal fragment of dynorphin A with m/z 1028 (DynA 10 -17) was detected in a few HD animals and exhibited a similar spatial distribution pattern as DynB and aNeo.…”

Section: Detection Of Other Dynorphin Related Peptides-several Dynorpmentioning

confidence: 99%

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L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry

Hanrieder

Karlsson

Fälth

et al. 2011

Pharmacological Reports

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Opioid peptides are involved in various pathophysiological processes, including algesia, epilepsy, and drug dependence. A strong association between L-DOPA-induced dyskinesia (LID) and elevated prodynorphin mRNA levels has been established in both patients and in animal models of Parkinson's disease, but to date the endogenous prodynorphin peptide products have not been determined. Here, matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) was used for characterization, localization, and relative quantification of striatal neuropeptides in a rat model of LID in Parkinson's disease. MALDI IMS has the unique advantage of high sensitivity and high molecular specificity, allowing comprehensive detection of multiple molecular species in a single tissue section. Indeed, several dynorphins and enkephalins could be detected in the present study, including dynorphin A(1-8), dynorphin B, ␣-neoendorphin, MetEnkRF, MetEnkRGL, PEnk (198 -209, 219 -229). IMS analysis revealed elevated levels of dynorphin B, ␣-neoendorphin, substance P, and PEnk (220 -229) in the dorsolateral striatum of high-dyskinetic animals compared with low-dyskinetic and lesion-only control rats. Furthermore, the peak-intensities of the prodynorphin derived peptides, dynorphin B and ␣-neoendorphin, were strongly and positively correlated with LID severity. Interestingly, these LID associated dynorphin peptides are not those with high affinity to opioid receptors, but are known to bind and activate also -and ⌬-opioid receptors. In addition, the peak intensities of a novel endogenous metabolite of ␣-neoendorphin lacking the N-terminal tyrosine correlated positively with dyskinesia severity. MALDI IMS of striatal sections from Pdyn knockout mice verified the identity of fully processed dynorphin peptides and the presence of endogenous des-tyrosine ␣-neoendorphin. Des-tyrosine dynorphins display reduced opioid receptor binding and this points to possible novel nonopioid receptor mediated changes in the striatum of dyskinetic rats. Because des-tyrosine dynorphins can only be detected by mass spectrometry, as no antibodies are available, these findings highlight the importance of MALDI IMS analysis for the study of molecular dynamics in neurological diseases. Molecular & Cellular

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mentioning

confidence: 93%

Section: Detection Of Other Dynorphin Related Peptides-several Dynorpmentioning

confidence: 99%

L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry

Hanrieder

Karlsson

Fälth

et al. 2011

Pharmacological Reports

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“…SP and dopamine regulation work in a positive feedback mechanism as dopamine can potentiate the release of SP 38,41 . Therefore, SP decline is seen in postmortem PD brains and in models that replicate the late stages of the disease [42][43][44] , as a secondary effect of dopaminergic degeneration. The functional role of SP in the regulation of neuroinflammation and dopaminergic neuron survival remains elusive.…”

Section: Neuroinflammation and Substance Pmentioning

confidence: 99%

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Martínez

Philipp

2016

J Neurol Neuromedicine

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This review addresses the role that substance P (SP) and its preferred receptor neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. The SP/NK1R complex is a key player in the interaction between the immune and nervous systems. A common effect of this interaction is inflammation. For this reason and because of the predominance in the human brain of the NK1R, its antagonists are attractive potential therapeutic agents. Preventing the deleterious effects of SP through the use of NK1R antagonists has been shown to be a promising therapeutic strategy, as these antagonists are selective, potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to clinical management of CNS inflammation.

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“…When peptide levels have been measured, some studies have found decreased met-enkephalin levels in either the caudate nucleus (Sivam, 1991) or the putamen (Taquet et al, 1983;Llorens-Cortes et al, 1984). Other studies have found no changes in met-enkephalin levels in either the caudate nucleus or the putamen (Fernandez et al, 1992).…”

Section: Abstract: Enkephalin; Striatum; Parkinsonism; Dopamine; Monmentioning

confidence: 99%

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

1999

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This study examined the extent of striatal dopamine (DA) denervation and coincident expression of preproenkephalin (PPE) mRNA in monkeys made parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Some animals (n ϭ 4) became moderately parkinsonian after receiving large doses of MPTP over short periods of time and were symptomatic for only a short period of time (1-3 months; acute parkinsonian group). Other animals became moderately parkinsonian after receiving either escalating doses of MPTP over long periods (4-6 months; n ϭ 5) or a high dose of MPTP over a short period (Ͻ1 month; n ϭ 1) and remained symptomatic for an extended period (Ͼ8 months; chronic parkinsonian group). Despite similar symptomatology and similar degrees of striatal DA denervation at the time of their deaths, only acute parkinsonian animals had significantly increased PPE expression in sensorimotor striatal regions. PPE expression in chronic parkinsonian animals was either not changed or significantly decreased in most striatal regions. These findings suggest that the duration and not the extent of striatal DA denervation is a critical factor in modulating changes in striatal PPE expression. Furthermore, these results question the role of increased activity in the enkephalin-containing indirect striatopallidal pathway in the expression of parkinsonian symptoms.

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Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem Parkinsonian brains

Cited by 51 publications

References 32 publications

L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry

L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

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