Drug-induced Parkinson’s disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb

BackgroundOlfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice.FindingsLesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission. MPTP induced motor impairment, but no deficit in olfactory search. Thyrosine hydroxylase did not differ in olfactory bulb, while a strong decrease was detected in substantia nigra and tegmentum of MPTP mice. Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in the inner granular layer of MPTP mice.ConclusionsMPTP mice do not present behavioural deficits in olfactory search, yet immunoreactivity reveals modifications in the olfactory bulb, and suggests changes in intracellular signal processing, possibly linked to neuron survival after MPTP.

• Publication year

  2017

• Venue

  Behavioral and Brain Functions

• Publication date

  2017-01-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12993-017-0119-2PMID 28122575PMCID 5267367
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Human behavioral assessments in current research of Parkinson's disease.

  2016cited by this paper
• Animal behavioral assessments in current research of Parkinson's disease.

  2016cited by this paper
• Dopamine or biopterin deficiency potentiates phosphorylation at (40)Ser and ubiquitination of tyrosine hydroxylase to be degraded by the ubiquitin proteasome system.

  2015cited by this paper
• Mechanisms of Dopamine D1 Receptor-Mediated ERK1/2 Activation in the Parkinsonian Striatum and Their Modulation by Metabotropic Glutamate Receptor Type 5

  2014cited by this paper
• Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3

  2013cited by this paper
• Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

  2013cited by this paper
• Parkinson’s disease mouse models in translational research

  2011cited by this paper
• Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro*

  2010cited by this paper
• Dopamine systems in the forebrain.

  2009cited by this paper
• Non‐motor symptoms in Parkinson’s disease

  2008cited by this paper
• Olfactory deficits in mice overexpressing human wildtype α‐synuclein

  2008cited by this paper
• Olfactory Dysfunction in Parkinson’s Disease

  2007cited by this paper
• Non-motor Symptoms of Parkinson's Disease

  2007cited by this paper
• The effect of neurodegenerative diseases on the subventricular zone

  2007cited by this paper
• Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.

  2006cited by this paper
• Differential effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the olfactory bulb and the striatum in mice.

  2005cited by this paper
• Selective alterations of gene expression in mice induced by MPTP

  2005cited by this paper
• Role of the Redox Protein Thioredoxin in Cytoprotective Mechanism Evoked by (-)-Deprenyl

  2005cited by this paper
• Distribution of D2 dopamine receptor in the olfactory glomeruli of the rat olfactory bulb

  2005cited by this paper
• Dopamine depletion impairs precursor cell proliferation in Parkinson disease

  2004cited by this paper
• Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice.

  2004cited by this paper
• Animal models of depression: olfactory lesions affect amygdala, subventricular zone, and aggression.

  2004cited by this paper
• Stages in the development of Parkinson’s disease-related pathology

  2004cited by this paper
• Regional variations in the localization of insoluble kinase A regulatory isoforms during rodent brain development.

  2004cited by this paper
• Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson's disease.

  2004cited by this paper
• Differential expression and ser897 phosphorylation of striatal N-methyl-d-aspartate receptor subunit NR1 in animal models of Parkinson's disease.

  2004cited by this paper
• Staging of brain pathology related to sporadic Parkinson's disease.

  2003cited by this paper
• Where Does Parkinson Disease Pathology Begin in the Brain?

  2002cited by this paper
• Modification of tyrosine hydroxylase activity by chloral derived β‐carbolines in vitro

  2002cited by this paper
• A novel mechanism of dopamine neurotoxicity involving the peripheral extracellular and the plasma membrane dopamine transporter

  2001cited by this paper
• Behavioral phenotyping of the MPTP mouse model of Parkinson's disease.

  2001cited by this paper
• Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acid type A receptors.

  1999cited by this paper
• Dopamine receptor subtypes modulate olfactory bulb γ-aminobutyric acid type A receptors

  1999cited by this paper
• Olfactory receptor neurons express D2 dopamine receptors

  1999cited by this paper
• Parallel modulation of striatal dopamine synthetic enzymes by second messenger pathways.

  1998cited by this paper
• Protein kinase A inhibitor attenuates levodopa-induced motor response alterations in the hemi-parkinsonian rat.

  1997cited by this paper
• Olfactory dysfunction in Parkinson's disease.

  1997cited by this paper
• Cognitive-motor dysfunction in Parkinson's disease.

  1996cited by this paper
• Inducible cAMP Early Repressor Can Modulate Tyrosine Hydroxylase Gene Expression after Stimulation of cAMP Synthesis*

  1996cited by this paper
• The anterior olfactory nucleus in Parkinson's disease

  1995cited by this paper
• Inhibitors of Type IV Phosphodiesterases Reduce the Toxicity of MPTP in Substantia Nigra Neurons In Vivo

  1995cited by this paper
• Bromocriptine, a dopamine D2 receptor agonist, inhibits adenylyl cyclase activity in rat olfactory epithelium.

  1993cited by this paper
• Lack of major olfactory dysfunction in MPTP‐induced parkinsonism

  1992cited by this paper
• Preliminary diagnosis of Parkinson's disease by olfactory bulb pathology.

  1992cited by this paper
• Dopamine D‐1 Receptor and Cyclic AMP‐Dependent Phosphorylation in Parkinson's Disease

  1987cited by this paper
• Development/plasticity/repair Camp Response Element-binding Protein Regulates Differentiation and Survival of Newborn Neurons in the Olfactory Bulb

  year unknowncited by this paper

• Non-motor Symptom Replication in Neurotoxic Mouse Models of Parkinson’s Disease: A Review and Guide

  2026cites this paper
• Effect of 6-OHDA growth hormone on the calcium binding proteins located in the bulbus olfactorius in Parkinson model rats

  2025cites this paper
• Leveraging animal models to understand non-motor symptoms of Parkinson's disease.

  2025cites this paper
• Phosphodiesterase-4 Inhibition in Parkinson’s Disease: Molecular Insights and Therapeutic Potential

  2023cites this paper
• Olfactory Neuroepithelium in Olfactory Cleft Polyps: Do They Have Any Effect on Olfaction Results After Endoscopic Sinus Surgery?

  2022cites this paper
• Olfactory neuroepithelium in the middle turbinate: is there any impact on olfaction function after lateral marsupialization for concha bullosa surgery?

  2021cites this paper
• How to Improve Behavioral Parent and Teacher Training for Children with ADHD: Integrating Empirical Research on Learning and Motivation into Treatment

  2020cites this paper
• A new sensitive and subunit‐selective molecular tool for investigating protein kinase A in the brain

  2020cites this paper
• Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain

  2020cites this paper
• Olfactory marker protein contributes to the evaluation of odour values by olfactory glomerular processing.

  2020cites this paper
• Protein Kinase A Distribution in Meningioma

  2019cites this paper
• Animal models of olfactory dysfunction in neurodegenerative diseases.

  2019cites this paper
• Olfactory receptor neurons express olfactory marker protein but not calpain 5 from the same genomic locus

  2019cites this paper
• Olfactory Dysfunction in Autoimmune Central Nervous System Neuroinflammation

  2018cites this paper
• Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression: Evidence from clinical studies and neurotoxin models.

  2018cites this paper