Alterations in brain gene expression and other factors associated with resistance and vulnerability to learned helplessness in rats.
Published: 2005
Language: eng
Number of pages: 226
Description: The precise etiology of depression remains unknown. Various parameters including gender, biochemical factors such as plasma homocysteine and genes mediating neuroplasticity, immune function and lipid metabolism have been implicated in major depression. The aim of this study was to determine if these factors are associated with resistance and/or vulnerability to depressive-type behaviour using the learned helplessness (LH) model. Male and female rodents exposed to the learned helplessness paradigm were subdivided into resistant (nLH) or vulnerable (LH) groups based on escape performance. Plasma and brain tissues were collected and biochemical, mRNA and behavioural analyses were carried out. Major results were as follows. (1) Vulnerability towards developing helplessness was not affected by gender or estrous phase (diestrus vs. estrus). (2) Plasma homocysteine levels were not different between LH and nLH animals. However, females showed higher levels in both LH and nLH groups, implying a stress-response which was not seen in males. (3) In situ hybridization revealed up- and down-regulation of genes relating to neuroplasticity, immune function and lipid metabolism, which was distinct in LH and nLH groups. Genes specifically altered in LH animals included (i) upregulation of TrkB receptor (males only), TrkC receptor, COX-2 and LACS-2. In nLH animals genes altered in various cortical areas included (ii) downregulation of the IL-10 receptor, PPAR-beta and bcl-2. This suggests that different mechanisms may be responsible for mediating resistance and vulnerability towards developing helplessness. Expression of TrkC receptor showed no alterations in LH or nLH animals. (4) Additional changes were also observed in response to stress, as seen in both LH and nLH groups compared to non-stressed controls. Such results were observed in plasma homocysteine levels and TrkB receptor mRNA levels exclusively in females and IL-6 receptor in males.Despite the fact that there were no observed gender differences in helpless behaviour, gender may be an important factor to consider not only in clinical depression but in stress response as well. Overall, these studies suggest that gene expression alterations exist in neuroplasticity, immune function and lipid metabolism in learned helplessness. These pathways may be involved in both the resistance and vulnerability towards developing helpless behaviour.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5339.

Thesis (Ph.D.)--University of Toronto, 2005.

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