Biochemical alteration in cerebrospinal fluid precedes behavioral deficits in Parkinsonian rats induced by 6-hydroxydopamine.
BACKGROUND
Parkinson's disease, affecting at least 1% of population older than 65 years, is the most common neurodegenerative movement disorder. Up to now, no evidence has demonstrated that biochemical changes in CSF occur preceding the onset of Parkinson's symptoms. In this study, we tested the hypothesis that biochemical changes in CSF precede behavioral deficits in Parkinsonian animals.


METHODS
We infused different doses of 6-OHDA into the MFB of rats bilaterally and examined the animals' movement behaviors, biochemical alterations in CSF, and dopaminergic neuronal number in the SNpc 1 week later.


RESULTS
Our results indicated that animals with over 70% dopaminergic neuronal loss in the SNpc exhibited behavioral bradykinesia and rigidity, and a decrease of HVA in CSF. In contrast, animals with about 42% dopaminergic neuronal loss in the SNpc showed normal movement behaviors, but displayed a drastic decline of HVA in CSF. Furthermore, the number of dopaminergic neurons in the SNpc was positively correlated with the HVA level in CSF.


CONCLUSIONS
Our findings demonstrate that biochemical alteration in CSF foreruns behavioral deficits and the HVA level in CSF is positively correlated with the number of dopaminergic neurons in the SNpc of Parkinsonian rats induced by 6-OHDA. Our results strongly suggest that additional studies are needed to evaluate usefulness of monitoring the HVA level in CSF for early detection of the loss of dopaminergic neurons in the SNpc that precedes the onset of Parkinsonian symptoms in humans.
Lin
Jia-Wei
JW
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110, Taiwan.
Shih
Chwen-Ming
CM
Chen
Yen-Chou
YC
Lin
Chien-Min
CM
Tsai
Jo-Ting
JT
Chiang
Yung-Hsiao
YH
Shih
Raymond
R
Chiu
Pei-Ling
PL
Hung
Kuo-Sheng
KS
Yeh
Yi-Shian
YS
Wei
Li
L
Chiu
Wen-Ta
WT
Yang
Liang-Yo
LY
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D018476:Hypokinesia / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009127:Muscle Rigidity / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology*; D013565:Sympatholytics / Q000633:toxicity
D015415:Biomarkers; D013565:Sympatholytics; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid