Depressive-like neurochemical and behavioral markers of Parkinson’s disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle

Kamińska, Kinga; Lenda, Tomasz; Konieczny, Jolanta; Czarnecka, Anna; Lorenc‐Koci, Elżbieta

doi:10.1016/j.pharep.2017.05.016

Cited by 41 publications

(30 citation statements)

References 30 publications

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“…We would argue that the former is more likely for the following reasons. First, our previous results confirmed depletion of dopamine on the lesioned side of the frontal cortex of rats that underwent the same treatment (Kamińska et al, 2017). Second, the expression of markers of glial activation (e.g., Gfap and Aif1) appeared normal and not indicative of glial proliferation.…”

Section: Discussionsupporting

confidence: 78%

“…6-OHDA-induced lesioning of dopamine neurons in rats is a widely used model of PD (Simola et al, 2007). Several studies demonstrated differences in IEG induction following administration of a D1like receptor agonist and the contents of dopamine and its metabolites between the lesioned and nonlesioned hemispheres in animals with unilateral 6-OHDA lesions, particularly in the striatum (Berke et al, 1998;Perese et al, 1989;Walker et al, 2013), and in the level of monoamine neurotransmitters in the substantia nigra, hippocampus and frontal cortex (Kamińska et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

Radlicka

Kamińska

Borczyk

et al. 2020

Preprint

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The development of Parkinson's disease (PD) causes dysfunction of the frontal cortex, which contributes to hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-DOPA alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. In this study, we investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed an RNA-seq analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesion that were treated with L-3,4-dihydroxyphenylalanine (L-DOPA) , for 2 weeks.We used analysis of variance to identify differentially expressed genes and found 48 genes with significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of 5 modules consisting of genes with similar expression patterns. The analyses led to three primary observations. First, the changes in gene expression induced by L-DOPA were bilateral, although only one hemisphere was lesioned. Second, the changes were not restricted to neurons but also appeared to emerge in immune or endothelial cells. Finally, comparisons with databases of drug-induced gene expression signatures revealed multiple nonspecific effects, which indicates that a part of the observed response is a common pattern activated by multiple types of pharmaceuticals in different target tissues.Taken together, our results identify cellular mechanisms in the frontal cortex that are involved in the response to L-DOPA treatment.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

Radlicka

Kamińska

Borczyk

et al. 2020

Preprint

Self Cite

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“…Dopamine depletions (Guiard et al, 2008) as well as chronic administration of 5 mg/kg d-AMP in adolescent rats enhance firing rates of NE neurons in the locus coeruleus, which projects to the prefrontal cortex (Labonte et al, 2012). That alterations in desipramine sensitivity were only noted with minimum response time is consistent with past work on desipramine's motoric effects (Weber et al, 2009) as well as the use of desipramine to treat motor impairment following DA depletions (Kamińska et al, 2017). Our findings show chronic administration of 1 mg/kg d-AMP in adolescence enhances sensitivity to the responseslowing effects of a high dose of desipramine, suggesting NE signaling is altered by lowdose adolescent d-AMP administration.…”

Section: Effects Of Adolescent D-amp On Sensitivity To D-amp Desiprasupporting

confidence: 75%

d-Amphetamine and methylmercury exposure during adolescence alters sensitivity to monoamine uptake inhibitors in adult mice

Boomhower

Newland

2019

NeuroToxicology

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Gestational exposure to methylmercury (MeHg), an environmental neurotoxicant, and adolescent administration of d-amphetamine (d-AMP) disrupt dopamine neurotransmission and alter voluntary behavior in adult rodents. We determined the impact of adolescent exposure to MeHg and dAMP on monoamine neurotransmission in mice by assessing sensitivity to acute dAMP , desipramine, and clomipramine, drugs that target dopamine, norepinephrine, and serotonin reuptake, respectively. Male C57Bl/6n mice were given 0 (control) or 3 ppm MeHg via drinking water from postnatal day 21 to 60 (murine adolescence). Within each group, mice were given once-daily injections of dAMP or saline (i.p.) from postnatal day 28 to 42. This exposure regimen produced four treatment groups (n = 10-12/group): control, dAMP , MeHg, and dAMP + MeHg. As adults, the mice lever pressed under fixed-ratio schedules of reinforcement (FR 1, 5, 15, 30, 60, and 120). Acute i.p. injections of dAMP (.3-1.7 mg/kg), desipramine (5.6-30 mg/kg), and clomipramine (5.6-30 mg/kg) were administered in adulthood after a stable behavioral baseline was established. Adolescent MeHg exposure increased saturation rate and minimum response time, an effect that was mitigated by chronic administration of dAMP in adolescence. In unexposed mice, the three monoamine reuptake inhibitors had separable behavioral effects. Adolescent dAMP increased sensitivity to acute dAMP , desipramine, and clomipramine. Adolescent MeHg exposure alone did not alter drug sensitivity. Combined adolescent dAMP + MeHg exposure enhanced sensitivity to acute d-AMP's and desipramine's effects on minimum response time. Adolescence is a vulnerable developmental period during which exposure to chemicals can have lasting effects on monoamine function and behavior.

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“…The 16 µg dose of 6-OHDA diminished the sucrose solution preference for 3% both in rats without and with desipramine pretreatment. Besides, 6-OHDA doses also affected the reduction of dopamine contents of brain structures on the ipsilateral side [ 103 ]. Haddadi et al (2015) administered 6-OHDA (8 µg/2 µL) unilaterally into the substantia nigra in male Wistar rats and assessed the catalepsy (bar test) and motor coordination (rotarod test) behavioral tests.…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

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Depressive-like neurochemical and behavioral markers of Parkinson’s disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle

Abstract: Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression.

Cited by 41 publications

References 30 publications

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

d-Amphetamine and methylmercury exposure during adolescence alters sensitivity to monoamine uptake inhibitors in adult mice

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

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