The Impact On Neurotransmitters Of Olfactory Bulb In Cynomolgus Monkeys Damaged By MPTP

Not confined to the traditional conception of PD, it may well have been classifiedas a primary olfactory disorder with secondary motor accompaniments. As a hinge ofolfactory pathway, the pathology of the olfactory bulb has been widely researched.MPTP-induced parkinsonism cynomolgus monkey model has been viewed as the mostideal model for the research of parkinsonism. The study aims to open out theneuroanatomical and neurochemical characteristics of cynomolgus monkey olfactorybulb via immunohistochemical methods. These characteristics include:1.the celluararchitecture of cynomolgus monkey olfactory bulb;2.the localization of glia cells andthe expression of the neurotransmitters in the multi-layered cynomolgus monkeyolfactory bulb;3.the effects of MPTP on the expressions of neurotransmitters and theimpacts on glia cells and cell apoptosis. the impact of MPTP injury on the majorneurotransmitters, apoptosis signals and glia cells via immunohistochemical me. Allthese provide fundamental knowledge for olfaction dysfunction of PD.Part I The making of the MPTP-induced parkinsonism cynomolgus monkey modelsMethods: Six adult healthy cynomolgus monkeys were taken care of in the centre of theanimals in accordance with the AAALAC(Association for Assessment andAccreditation of Laboratory Animal Care). Three animals were received intravenousinjections of MPTP(0.2mg kg)under the individualization principle everymorning(9:00am).Injections ceased when typical clinical symptoms emerged. The otherthree adult cynomolgus monkeys were as a control group.Results:10~14days after injections, all the three monkeys showed a parkinsonismcharacterized by bradykinesia, loss of spontaneous activity, buckling posture,impairments of balance, myotonia, discontinuous rigidity, postural or static tremorthat reached a disability scale of10and a week later the disease progressed and remained stable scoring19.5±4.8.PartⅡ The impact on neurotransmitters of olfactory bulb in cynomolgus monkeysdamaged by MPTPMethods: The olfactory bulbs of MPTP group and normal group monkeys weretransected and made into paraffin sections.25sections from each group wereimmunostained for DA and5-HT respectively.5sections were selected out randomly toobtain digital images with a digital camera coupled to an Olympus IX71microscope.These images were analyzed. We measured the mean optical density and counted thepositive cell numbers via a IPP software to analyze these images.Following the same procedure, then we examined the expressions of GABA and ChATwhich were both amino acid neurotransmitters in cynomolgus olfactory bulb.Also we examined the expressions of D1R、D2R、DARPP32、DAT in cynomolgusmonkey olfactory bulb.Results: The number of these transmitter positive cells and the mount of the positivefibers decreased.Part Ⅲ the impact on glia cells of olfactory bulb in cynomolgus monkeys damaged byMPTPMethods: Immunohistochemical staining was performed to examine the localization andexpression of Iba1、GFAP and TNF-α in the olfactory bulb both normal and MPTPgroup monkeys. We measured the numbers of these positive cells and the mean opticaldensity of these positive elements to reflect the impact on glia cells of MPTP toxicity.Results: The positive elements of Ibal、GFAP and TNF-αincreased.Part Ⅳ the impact on cell apoptosis of olfactory bulb in cynomolgus monkeys damagedby MPTPMethods: Immunohistochemical staining was performed to examine the localization andexpressions of Bcl2and caspase3in the cynomolgus monkey olfactory bulb. Wemeasured the numbers of these positive cells and the mean optical density of these positive elements to reflect the impact on cell apoptosis of MPTP toxicity.Results: Bcl2positive elements decreased and caspase3positive elements increased.Conclusions: MPTP toxicity causes altered neurotransmitters,abnormal cell apoptosisand glia cell hyperplasia and inflammation.