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Study · Animal study (in vivo) · mouse · 2023

9 results

Peripheral MC1R Activation Modulates Immune Responses and is Neuroprotective in a Mouse Model of Parkinson's Disease.

Srivastava P, Nishiyama S, Zhou F, Lin SH, Srivastava A, Su C, Xu Y, Peng W, Levy M, Schwarzschild M, Chen X

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology19 Dec 2023Cited by 12 (Europe PMC)

PMID38110615 (opens in a new tab)PMCIDPMC10769915 (opens in a new tab)DOI10.1007/s11481-023-10094-7 (opens in a new tab)PepBankPUB-38110615
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Summary

BackgroundMelanocortin 1 receptor (MC1R) is a key pigmentation gene, and loss-of-function of MC1R variants that produce red hair may be associated with Parkinson's disease (PD). We previously reported compromised dopaminergic neuron survival in Mc1r mutant mice and dopaminergic neuroprotective effects of local injection of a MC1R agonist to the brain or a systemically administered MC1R agonist with appreciable central nervous system (CNS) permeability. Beyond melanocytes and dopaminergic neurons, MC1R is expressed in other peripheral tissues and cell types, including immune cells. The present study investigates the impact of NDP-MSH, a synthetic melanocortin receptor (MCR) agonist that does not cross BBB, on the immune system and the nigrostriatal dopaminergic system in mouse model of PD.MethodsC57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed. Peripheral and CNS immune cells were phenotyped and inflammatory markers were measured. The nigrostriatal dopaminergic system was assessed behaviorally, chemically, immunologically, and pathologically. To understand the role of regulatory T cells (Tregs) in this model, CD25 monoclonal antibody was used to deplete CD25 + Tregs.ResultsSystemic NDP-MSH administration significantly attenuated striatal dopamine depletion and nigral dopaminergic neuron loss induced by MPTP + LPS. It improved the behavioral outcomes in the pole test. Mc1r mutant mice injected with NDP-MSH in the MPTP and LPS paradigm showed no changes in striatal dopamine levels suggesting that the NDP-MSH acts through the MC1R pathway. Although no NDP-MSH was detected in the brain, peripheral, NDP-MSH attenuated neuroinflammation as observed by diminished microglial activation in the nigral region, along with reduced TNF-α and IL1β levels in the ventral midbrain. Depletion of Tregs was associated with diminished neuroprotective effects of NDP-MSH.ConclusionsOur study demonstrates that peripherally acting NDP-MSH confers protection on dopaminergic nigrostriatal neurons and reduces hyperactivated microglia. NDP-MSH modulates peripheral immune responses, and Tregs may be involved in the neuroprotective effect of NDP-MSH.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, systemic NDP-MSH significantly attenuated striatal dopamine depletion versus vehicle.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH reduced the loss of dopamine in the striatum compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseStriatal dopamine level
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    Systemic NDP-MSH administration significantly attenuated striatal dopamine depletion
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, systemic NDP-MSH significantly attenuated nigral dopaminergic neuron loss versus vehicle.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH reduced the loss of dopamine neurons compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreaseNigral dopaminergic neuron survival
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    Systemic NDP-MSH administration significantly attenuated striatal dopamine depletion and nigral dopaminergic neuron loss
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, NDP-MSH improved behavioral outcomes in the pole test versus vehicle.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH improved pole test performance compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    IncreasePole test behavior
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    It improved the behavioral outcomes in the pole test.
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In Mc1r mutant mice given MPTP and LPS, NDP-MSH produced no change in striatal dopamine levels.

    In plain wordsIn mice with a mutated Mc1r gene, NDP-MSH did not change striatal dopamine levels.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    No significant changeStriatal dopamine in Mc1r mutant mice
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    Mc1r mutant mice injected with NDP-MSH in the MPTP and LPS paradigm showed no changes in striatal dopamine levels suggesting that the NDP-MSH acts through the MC1R pathway.
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  5. 05AnimalAnimal study (in vivo)Pharmacokinetics

    In mice given NDP-MSH systemically, no NDP-MSH was detected in the brain.

    In plain wordsIn mice given NDP-MSH, no NDP-MSH was found in the brain.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    Not applicableNDP-MSH detection in brain
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    Although no NDP-MSH was detected in the brain
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, NDP-MSH attenuated neuroinflammation with diminished microglial activation in the nigral region.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH reduced microglial activation in the nigral region compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseMicroglial activation in nigral region
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    NDP-MSH attenuated neuroinflammation as observed by diminished microglial activation in the nigral region
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, NDP-MSH reduced TNF-α levels in the ventral midbrain.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH lowered TNF-α in the ventral midbrain compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseTNF-α level in ventral midbrain
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    reduced TNF-α and IL1β levels in the ventral midbrain
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In mice given MPTP and LPS, NDP-MSH reduced IL1β levels in the ventral midbrain.

    In plain wordsIn mice with a Parkinson's-like model, NDP-MSH lowered IL1β in the ventral midbrain compared with vehicle.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseIL1β level in ventral midbrain
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    reduced TNF-α and IL1β levels in the ventral midbrain
    1 context sentence
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.
  9. 09AnimalAnimal study (in vivo)Mechanism

    In mice given MPTP and LPS, depletion of CD25+ regulatory T cells was associated with diminished neuroprotective effects of NDP-MSH.

    In plain wordsIn mice with a Parkinson's-like model, removing regulatory T cells was linked to weaker protection by NDP-MSH.

    Peptide
    Melanotan I (afamelanotide)
    Outcome
    DecreaseNeuroprotection after Treg depletion
    Study

    mousen: not reported in source

    MPTP and LPS model of Parkinson's disease
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    400 µg/kg · systemic · day 1 to day 12As given in this study (mouse).

    Source sentences

    Summary
    Depletion of Tregs was associated with diminished neuroprotective effects of NDP-MSH.
    2 context sentences
    Summary · context
    To understand the role of regulatory T cells (Tregs) in this model, CD25 monoclonal antibody was used to deplete CD25 + Tregs.
    Summary · context
    C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

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