Modulation of Adult Neurogenesis in the Olfactory Bulb in an Acute Mouse Model of Parkinson´s Disease

Hyposmia, often preceding the cardinal motor symptoms, such as bradykinesia, rigidity, tremor at rest and postural instability, is frequently reported in PD. This symptom appears to be related to an increased number of dopamine neurons in the periglomerular layer (PGL) of the OB. In the histological...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: CHIU, Wei-Hua
Beteiligte: Ries, V. (PD Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2013
Nervenheilkunde
Ausgabe:http://dx.doi.org/10.17192/z2013.0704
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Zusammenfassung:Hyposmia, often preceding the cardinal motor symptoms, such as bradykinesia, rigidity, tremor at rest and postural instability, is frequently reported in PD. This symptom appears to be related to an increased number of dopamine neurons in the periglomerular layer (PGL) of the OB. In the histological study, we have investigated the survival and neuronal differentiation of NPC in the OB, following L-DOPA and/or Selegiline in a unilateral, intranigral 6-OHDA lesion model in mice. Our data show that the number of NPC in the SVZ is decreased after 6-OHDA lesion, while there is no difference from control in lesioned mice with Selegiline or L-DOPA treatment. Moreover, the monoamine oxidase-B inhibitor, Selegiline, is able to normalize the number of dopamine neurons by increasing the number of TUNEL+ cell and reverses the dopaminergic differentiation to control in the PGL, while L-DOPA treatment sustains the increased number, by increasing the survival of NPC and upregulating 2-fold dopaminergic differentiation observed in 6-OHDA lesioned animals. In the behavioral study, to understand the olfactory function after 6-OHDA lesion and the effects of Selegiline treatment, six different experimental groups were investigated and performed an olfactory discrimination test. The data show that a delayed olfactory deficit was first appeared 12 weeks post 6-OHDA lesion and the recovery of olfactory function followed a daily, chronic treatment of Selegiline for additional 12 weeks. However, the olfactory dysfunction of the animals relapses again after a 4-week withdrawal of Selegiline treatment. To combine the findings of our studies, we conclude that there is a distinct modulation of newly generated dopamine neurons of the OB after L-DOPA and/or Selegiline treatment. Furthermore, a delayed olfactory deficit was detected after a downregulation of adult neurogenesis, and only a chronic, continuous treatment of Selegiline can reverse the olfactory dysfunction in an acute mouse model of PD. Our findings provide practical implications and stimulate further clinical and preclinical research, bridging the basic knowledge of hyposmia of PD from bench to bedside. Although the relationship of hyposmia and an increased number of dopamine neurons in the OB of PD patients is not well defined yet, the evidence in this study may offer the explanation, that the dysregulation of adult neurogenesis might be one of reasons to cause hyposmia of PD. Moreover, the effects of Selegiline on olfactory function could be a consideration for clinical application. However, further studies are needed to show whether the interaction of dopamine depletion and drug treatment plays a role in olfactory function in PD patients.
DOI:http://dx.doi.org/10.17192/z2013.0704