Age- and sex-differences in the nitric oxide synthase expression and dopamine concentration in the murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Parkinson's disease (PD) is an age- and sex-related neurodegenerative disorder of unknown aetiology. The involvement of nitric oxide synthase (NOS) in the etiopathogenesis of PD is quite well documented. We decided to examine changes in dopamine (DA) levels as well as iNOS, nNOS, eNOS mRNA and protein expression in the striatum of C57BL male and female (2- and 12-month old) mice in the course of PD-related neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The significantly decreased level of DA was previously observed in male than in female, irrespective of age. In young mice the recovery of DA was significantly greater in female compared to male mice. On the contrary, both in male and female old animals the low concentration of DA was extended up to 21 days post MPTP injection. The increases in iNOS protein expression post MPTP intoxication occurred more rapidly in male (young and old) than in female mice. The pattern of changes in iNOS protein expression was also different in young versus aged mice. nNOS protein expression increased earlier in young male than young female mice. No changes were observed in eNOS expression. In conclusion, our results support the hypothesis of the involvement of iNOS and nNOS, but not eNOS in neurodegenerative processes. Our findings suggest that age- and sex-differences in DA concentration and iNOS expression as well as sex-differences of nNOS expression after intoxication may depend on the increased susceptibility of males as well as older animals to toxic effect of MPTP and aggravated process of recovery in old brains.
Joniec
Ilona
I
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmiescie 26/28 00-927, Warsaw, Poland. joniec@amwaw.edu.pl
Ciesielska
Agnieszka
A
Kurkowska-Jastrzebska
Iwona
I
Przybylkowski
Adam
A
Czlonkowska
Anna
A
Czlonkowski
Andrzej
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D020267:MPTP Poisoning / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013997:Time Factors
D012333:RNA, Messenger; D015102:3,4-Dihydroxyphenylacetic Acid; D019001:Nitric Oxide Synthase; D004298:Dopamine; D006719:Homovanillic Acid