PINK1 deficiency is associated with increased deficits of adult hippocampal neurogenesis and lowers the threshold for stress-induced depression in mice
| Autor: | Benjamin K. Yee, Lianteng Zhi, Hansruedi Büeler, Wayne A. Cass, Liuke Sun, Ruifang Shen, Sandeep Kumar Agnihotri, Marilyn J. Duncan, Ravi Shankar Akundi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Hypothalamo-Hypophyseal System Neurogenesis Hippocampus Pituitary-Adrenal System Hippocampal formation Anxiety Motor Activity 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Receptors Glucocorticoid Corticosterone Internal medicine medicine Animals Chronic stress Swimming 030304 developmental biology Cell Proliferation Neurons 0303 health sciences Depressive Disorder Behavior Animal business.industry Depression Dentate gyrus Cell Differentiation Parkinson Disease Anxiety Disorders Tail suspension test Temporal Lobe Mice Inbred C57BL Disease Models Animal Endocrinology chemistry Dentate Gyrus business Protein Kinases 030217 neurology & neurosurgery Stress Psychological Behavioural despair test |
| Zdroj: | Behavioural brain research. 363 |
| ISSN: | 1872-7549 |
| Popis: | Parkinson's disease (PD) is characterized by motor impairments and several non-motor features, including frequent depression and anxiety. Stress-induced deficits of adult hippocampal neurogenesis (AHN) have been linked with abnormal affective behavior in animals. It has been speculated that AHN defects may contribute to affective symptoms in PD, but this hypothesis remains insufficiently tested in animal models. Mice that lack the PD-linked kinase PINK1 show impaired differentiation of adult-born neurons in the hippocampus. Here, we examined the relationship between AHN deficits and affective behavior in PINK1-/- mice under basal (no stress) conditions and after exposure to chronic stress. PINK1 loss and corticosterone negatively and jointly affected AHN, leading to lower numbers of neural stem cells and newborn neurons in the dentate gyrus of corticosterone-treated PINK1-/- mice. Despite increased basal AHN deficits, PINK1-deficient mice showed normal affective behavior. However, lack of PINK1 sensitized mice to corticosterone-induced behavioral despair in the tail suspension test at a dose where wildtype mice were unaffected. Moreover, after two weeks of chronic restraint stress male PINK1-/- mice displayed increased immobility in the forced swim test, and protein expression of the glucocorticoid receptor in the hippocampus was reduced. Thus, while impaired AHN as such is insufficient to cause affective dysfunction in this PD model, PINK1 deficiency may lower the threshold for chronic stress-induced depression in PD. Finally, PINK1-deficient mice displayed reduced basal voluntary wheel running but normal rotarod performance, a finding whose mechanisms remain to be determined. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect