Impact of astrocytes and gliogenesis on the pathophysiology of depression
Year: 2013
Type: dissertation
Abstract: Major depression is a highly prevalent disorder that poses a significant social burden in society nowadays. The pathophysiology of this disease is still poorly understood but growing evidence suggests that impaired neuroplasticity may be a key underlying mechanism for the precipitation of the disorder. This theory is substantiated by the fact that depression leads to a decrease in neurogenesis and several antidepressants (ADs) stimulate hippocampal neurogenesis, but it is still unclear if these pro-neurogenic effects are responsible for their mood-, emotional- and cognitive-improving actions. Recent studies also showed an important role for astrocytes in the pathophysiology of this disorder, which are crucial for neurotransmission and neurovascular coupling, evidenced by astrocytes loss in major depressive disorder (MDD). However, the importance of astrocytes in the precipitation of and recovery from MDD is still largely unknown. Therefore, we proposed to study the role of astrocytes and adult gliogenesis, more precisely the generation of new astrocytes, in the precipitation of and recovery from depressive-like cognitive behavior in rats both untreated and treated with ADs in a longitudinal manner - at short-term, long-term and recurrence perspective -, using a pre-validated model of depression - the unpredictable chronic mild stress (uCMS). Regarding the cognitive behavior assessment, although short-term memory seems to be impaired through the course of the disease, at short-term, long-term and recurrence, administration of fluoxetine and imipramine was effective in reverting the cognitive impairments induced by depression. The longterm memory was also highly affected by this disorder in all analyzed time-points, but the treatment with the ADs was not effective in reverting the cognitive impairments observed. Regarding the hippocampal dentate gyrus (DG) astrocytic population, at the long-term perspective of the disease, imipramine, but not fluoxetine, was able to elicit a strong pro-gliogenic effect. The same does not happen at recurrence for both ADs, suggesting that an adaptation to the stressful environment by these specific type of cells might be happening throughout time. Thereby, we provide some consistent evidences for the causative implication of gliogenesis and astrocytes in the pathophysiology of depression, having significant impacts in the long-term development and maintenance of cognitive deficits, as well as in the long-term recovery of those impairments by ADs. Our results endorse the view of the adult hippocampal DG gliogenesis process as a promising therapeutical target in future therapies in the neuropsychiatric field. Moreover, this study shows for the first time that alterations in the hippocampal DG resident astrocytes can be further analyzed as a predictive target for depression.
Author: Ana Rita Machado dos Santos
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2612136409