Loss of D 3 receptors in the zitter mutant rat is not reversed by l -dopa treatment

Autor: Diane Hagner, Shuichi Ueda, Jeffrey N. Joyce, T.C. Der, Tracy Osredkar, Shin Ichi Sakakibara, Lynn Renish, Maria Reploge
Rok vydání: 2004
Předmět:
Male
Heterozygote
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Nerve Tissue Proteins
Tropomyosin receptor kinase B
Nucleus Accumbens
Rats
Mutant Strains
Antiparkinson Agents
Levodopa
Rats
Sprague-Dawley
chemistry.chemical_compound
Prosencephalon
Parkinsonian Disorders
Developmental Neuroscience
Dopamine receptor D3
Dopamine
Internal medicine
medicine
Animals
Receptor
trkB
RNA
Messenger
Neurotransmitter
Receptor
Dopamine transporter
Dopamine Plasma Membrane Transport Proteins
Membrane Glycoproteins
Tyrosine hydroxylase
biology
Receptors
Dopamine D2
Brain-Derived Neurotrophic Factor
Homozygote
Receptors
Dopamine D3
Membrane Transport Proteins
Olfactory Pathways
Rats
Neostriatum
Disease Models
Animal
Oxidative Stress
Endocrinology
nervous system
Neurology
chemistry
Carbidopa
Disease Progression
biology.protein
Islands of Calleja
medicine.drug
Zdroj: Experimental Neurology. 187:178-189
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2004.01.012
Popis: In Parkinson's disease (PD) and animal models of parkinsonism the destruction of nigrostriatal (NSB) system results in a marked loss of the dopamine D3 receptor and mRNA in the islands of Calleja (ICj) and the nucleus accumbens shell (NAS). In animal models, it has been reported that both measures are elevated by repeated intermittent administration of l -dopa. However, a large proportion of PD cases are resistant to l -dopa-induced elevation of D3 receptor number. The zitter mutant (Zi/Zi) rat replicates the slow progressive degeneration of the NSB observed in PD and also exhibits a loss of D3 receptor number in the NAS or ICj. To test if this could be reversed with subchronic l -dopa treatment, injections of carbidopa (10 mg/kg ip) were followed an hour later with injection of l -dopa (100 mg/kg ip) twice a day for 10 days. In control Sprague–Dawley (SD) and zitter heterozygote (Zi/−) rats that do not show a loss of D3 receptors with vehicle treatment, l -dopa produced no change in D3 receptor number or in DA terminal density as measured by dopamine transporter (DAT) binding and tyrosine hydroxylase immunoautoradiography (TH-IR). There was a marked loss of DAT and TH-IR in caudate–putamen (CPu) and NA, as well as D3 receptors in NAS and ICj in Zi/Zi rats but no further change with l -dopa treatment. To determine if the resistance to l -dopa-induced increase in D3 receptor was due to a deficiency in expression of cortical BDNF or its receptor, TrkB, in CPu and NAS, we examined BDNF mRNA by ISHH in frontal cortex and TrkB mRNA in frontal cortex, CPu, and NA. The loss of the NSB in the Zi/Zi did not alter levels of BDNF or TrkB mRNA, nor did l -dopa administration alter levels BDNF or TrkB mRNA. Thus, unlike in 6-hydroxydopamine-treated rats, in Zi/Zi rats administered l -dopa does not reverse the loss of BDNF mRNA or lead to an elevation of D3 receptor number.
Databáze: OpenAIRE
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