Effect And Mechanism Of Thioredoxin 1 On Olfactory Dysfunction In Parkinson’s Disease Mice

Parkinson’s disease(PD)is characterized by progressive loss of Dopamine(DA)neurons in the substantia nigra pars compacta(SNpc)of the brain and the formation of Lewy bodies.Olfactory disorder is the most characteristic early non-motor symptom of PD,but its pathogenesis is still unclear.The olfactory bulb(OB)is the first relay station for olfactory processing,and its function relies on subventricular zone(SVZ).The neuroblasts produced by neural stem cells in SVZ migrate along the rostral migratory stream(RMS)to the olfactory bulb,differentiate into mature granule cells and glomerular cells,and then integrate into the synaptic circuit of the olfactory bulb to participate in the formation of olfactory information network.Thioredoxin 1(Trx1)plays a key role in regulating the redox state of cells.It can promote neural differentiation,regeneration and protect dopaminergic neurons in the substantia nigra.However,the role and mechanism of Trx-1 in regulating SVZ neurogenesis and improving olfactory dysfunction in PD mice are unclear.This study focuses on the role and mechanism of Trx-1 in olfactory dysfunction in PD mice.The research results are as follows:(1)Trx1 improves olfactory dysfunction in PD mice.After MPTP injection to mice,the olfactory perception and odor discrimination ability were impaired,and Trx1 overexpression significantly improved the olfactory dysfunction caused by MPTP.(2)Trx1 improves MPTP-induced reduction in neurogenesis.After MPTP administration in wild-type mice,neural stem cells,neuroblasts,and newborn neurons in the SVZ,neuroblasts in RMS,neuroblasts and mature neurons in OB,decreased significantly.Trx1 overexpression resisted the reduction in the number of neural cells induced by MPTP.(3)Trx1 regulates the neurogenesis in PD mice through D1R、CREB and cyclin D1.The expression levels of D1 R,p-CREB,and cyclin D1 in the SVZ region significantly decreased by MPTP.Trx1 overexpression restored the decrease of D1 R,p-CREB,and cyclin D1 by MPTP.The above studies indicate that Trx1 regulates the expression of D1R、CREB、cyclin D1,promotes the proliferation of neural stem cells in SVZ,increases the number of new-born neurons,promotes the migration of neuroblasts,increases the number of new-born neurons and mature neurons in OB,which results in improving the olfactory dysfunction in PD mice.