Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa

Yukihisa Funamizu; Haruo Nishijima; Tatsuya Ueno; Shinya Ueno; Hiroki Mizukami; Soroku Yagihashi; Masahiko Tomiyama

doi:10.1016/j.neures.2017.03.010

Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa

Neurosci Res. 2017 Aug;121:49-53. doi: 10.1016/j.neures.2017.03.010. Epub 2017 Apr 6.

Authors

Yukihisa Funamizu¹, Haruo Nishijima², Tatsuya Ueno³, Shinya Ueno⁴, Hiroki Mizukami⁵, Soroku Yagihashi⁶, Masahiko Tomiyama⁷

Affiliations

¹ Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori 030-8553, Japan; Department of Pathology and Molecular Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: operationalbigsafe@gmail.com.
² Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori 030-8553, Japan; Department of Neurophysiology, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: hnishijima-tky@umin.ac.jp.
³ Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori 030-8553, Japan; Department of Neurophysiology, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: tatsuya_ueno@med.pref.aomori.jp.
⁴ Department of Neurophysiology, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: shinyau@hirosaki-u.ac.jp.
⁵ Department of Pathology and Molecular Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: hirokim@hirosaki-u.ac.jp.
⁶ Department of Pathology and Molecular Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: yagihasi@hirosaki-u.ac.jp.
⁷ Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori 030-8553, Japan; Department of Neurophysiology, Hirosaki University, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: masahiko_tomiyama@med.pref.aomori.jp.

PMID: 28392304
DOI: 10.1016/j.neures.2017.03.010

Abstract

The mechanisms of dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) remain unclear, although it is known that the nucleus accumbens (NAc) plays a role in its development. Based on the hypothesis that DDS and levodopa-induced dyskinesia (LID) share a pathophysiological basis, we investigated dendritic spine morphology of medium spiny neurons (MSNs) in the NAc of a rat model of LID, because spine enlargement in MSNs of the caudate/putamen has been proposed to be a morphological hallmark of LID. Spines of NAc MSNs also became enlarged in the LID model. This result suggests that excitatory supersensitivity of MSNs in the NAc is involved in the development of DDS, similar to what occurs in the caudate/putamen in LID.

Keywords: Dendritic spine morphology; Dopamine dysregulation syndrome; Levodopa-induced dyskinesia; Nucleus accumbens.

MeSH terms

Animals
Apomorphine / pharmacology
Dendritic Spines / drug effects*
Dendritic Spines / metabolism
Disease Models, Animal
Dopamine Agents / therapeutic use*
Levodopa / therapeutic use*
Male
Medial Forebrain Bundle / drug effects
Medial Forebrain Bundle / injuries
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Neurons / pathology*
Nucleus Accumbens / pathology*
Oxidopamine / toxicity*
Parkinson Disease, Secondary* / chemically induced
Parkinson Disease, Secondary* / drug therapy
Parkinson Disease, Secondary* / pathology
Rats
Rats, Wistar
Statistics, Nonparametric
Sympatholytics / toxicity*
Time Factors
Tyrosine 3-Monooxygenase / metabolism

Substances

Dopamine Agents
Sympatholytics
Levodopa
Oxidopamine
Tyrosine 3-Monooxygenase
Apomorphine