Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress

Evans, JM; Sun, Yuhui; McGregor, Ailsa L.; Connor, Bronwen

doi:10.1016/j.neuropharm.2012.08.012

Cited by 132 publications

(91 citation statements)

References 83 publications

(116 reference statements)

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“…Data from clinical and preclinical studies suggested that inflammatory cytokines increased in depressed patients and in animal models of depression, and the inhibition of the inflammatory processes might ameliorate their depressive symptoms [40]. Thymol exhibited strong anti-inflammatory activities in the models of osteoarthritis [20], asthma [21], skin inflammation [41], ear edema [42], and peritonitis [43] etc.…”

Section: Effects Of Thymol On Inflammationmentioning

confidence: 99%

Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice

Deng

Chen

et al. 2015

Behavioural Brain Research

125

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Section: Effects Of Thymol On Inflammationmentioning

confidence: 99%

Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice

Deng

Chen

et al. 2015

Behavioural Brain Research

125

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“…Social isolation as a stressor has been associated with reductions in tissue and plasma allopregnanolone and the expression of the rate-limiting enzyme in allopregnanolone production, 5α-reductase, indicating that stressful events may have a direct effect on neurosteroidogenesis [20,21]. Altered neurosteroid levels are also linked with various anxiety-like behaviours in both rodent models and humans [22,23,24], implicating this neurosteroid pathway in mediating some of the programming effects of prenatal stress exposure. …”

Section: Introductionmentioning

confidence: 99%

Prenatal Stress Alters Hippocampal Neuroglia and Increases Anxiety in Childhood

et al. 2015

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Prenatal stress has been associated with detrimental outcomes of pregnancy, including altered brain development leading to behavioural pathologies. The neurosteroid allopregnanolone has been implicated in mediating some of these adverse outcomes following prenatal stress due to its potent inhibitory and anxiolytic effects on the brain. The aims of the current study were to characterise key markers for brain development as well as behavioural parameters, adrenocortical responses to handling and possible neurosteroid influences towards outcomes in guinea pig offspring in childhood. Pregnant guinea pig dams were exposed to strobe light for 2 h (9-11 a.m.) on gestational days 50, 55, 60, and 65 and were left to deliver spontaneously at term and care for their litter. Behavioural testing (open-field test, object exploration test) of the offspring was performed at postnatal day 18 (with salivary cortisol and DHEA measured), and brains were collected at post-mortem on day 21. Markers of brain development myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry, and the neurosteroid allopregnanolone and its rate-limiting enzymes 5α-reductase types 1 and 2 (5αR1/2) were measured in neonatal brains by radioimmunoassay, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot, respectively. Brain-derived neurotrophic factor protein was measured as a marker of synaptic plasticity, and GABA_A receptor subunit expression was also assessed using RT-PCR. Neonates born from mothers stressed during late pregnancy showed a reduction in both MBP (p < 0.01) and GFAP (p < 0.05) expression in the CA1 region of the hippocampus at 21 days of age. Pups of prenatally stressed pregnancies also showed higher levels of anxiety and neophobic behaviours at the equivalent of childhood (p < 0.05). There were no significant changes observed in allopregnanolone levels, 5αR1/2 expression, or GABA_A receptor subunit expression in prenatally stressed neonates compared to controls. This study shows alterations in markers of myelination and reactive astrocytes in the hippocampus of offspring exposed to prenatal stress. These changes are also observed in offspring that show increased anxiety behaviours at the equivalent of childhood, which indicates ongoing structural and functional postnatal changes after prenatal stress exposure.

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“…Besides, MP does not restrict animal movement throughout the study [22,23]. Generally, animals' exposure to the restricted space that limits their locomotor activities [24] and isolation, can elevate their plasma corticosterone levels, indicating their behavioral and biochemical vulnerability to both immobilization and isolation effects [25,26]. Modified-MP technique can obviate some of the aforementioned behavioral abnormalities [23].…”

Section: Resultsmentioning

confidence: 99%