Exp Neurobiol.  2019 Apr;28(2):289-299. 10.5607/en.2019.28.2.289.

Delayed Treatment of Capsaicin Produces Partial Motor Recovery by Enhancing Dopamine Function in MPP⁺-lesioned Rats via Ciliary Neurotrophic Factor

• Kim KI
• Baek JY
• Jeong JY
• Nam JH
• Park ES
• Bok E
• Shin WH
• Chung YC
• Jin BK

• KMID: 2450220
• DOI: http://doi.org/10.5607/en.2019.28.2.289

Abstract

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP⁺-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP⁺-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP⁺. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.

Keyword

Parkinson's disease; Astrocyte; Dopaminergic neuron; TRPV1; Ciliary neurotrophic factor

MeSH Terms

Animals
Antibodies, Neutralizing
Astrocytes
Capsaicin*
Ciliary Neurotrophic Factor*
Dopamine*
Dopaminergic Neurons
Medial Forebrain Bundle
Models, Animal
Neurons
Parkinson Disease
Pars Compacta
Rats*
Receptor, Ciliary Neurotrophic Factor
Tyrosine 3-Monooxygenase
Antibodies, Neutralizing
Capsaicin
Ciliary Neurotrophic Factor
Dopamine
Receptor, Ciliary Neurotrophic Factor
Tyrosine 3-Monooxygenase