Effect of adolescent androgen manipulation on psychosis-like behaviour in adulthood in BDNF heterozygous and control mice

Du, Xin; McCarthny, C.R.; Notaras, Michael; Buuse, Maarten van den; Hill, Robert A.

doi:10.1016/j.yhbeh.2019.03.005

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…Our results suggest that AR activation attenuates dopamine synthesis and presynaptic loading in the ventral tegmental area, and that its inactivation potentiates synthesis and vesicular loading. This is in accordance to previous results in which it has been observed that androgens decrease tyrosine hydroxylase (TH) expression in ventral tegmental area and substantia nigra ( 45 ) in a mechanism related to apoptosis ( 46 , 47 ), as well as expression of dopamine transporter (DAT) (the translational product of Slc6a3 ) in prefrontal cortex ( 48 ). In contrast, in distinct experimental setups androgens might also exert upregulatory activities on dopaminergic system.…”

Section: Discussionsupporting

confidence: 93%

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain

Amaya,

Sips,

Viho

et al. 2024

Front. Endocrinol.

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Glucocorticoids are key executors of the physiological response to stress. Previous studies in mice showed that the androgen receptor (AR) influenced the transcriptional outcome of glucocorticoid treatment in white and brown adipocytes and in the liver. In the brain, we observed that chronic hypercorticism induced changes in gene expression that tended to be more pronounced in male mice. In the present study, we investigated if glucocorticoid signaling in the brain could be modulated by androgen. After chronic treatment with corticosterone, dihydrotestosterone, a combination of both, and corticosterone in combination with the AR antagonist enzalutamide, we compared the expression of glucocorticoid receptor (NR3C1, also abbreviated GR) target genes in brain regions where AR and GR are co-expressed, namely: prefrontal cortex, hypothalamus, hippocampus, ventral tegmental area and substantia nigra. We observed that androgen affected glucocorticoid signaling only in the prefrontal cortex and the substantia nigra. Dihydrotestosterone and corticosterone independently and inversely regulated expression of Sgk1 and Tsc22d3 in prefrontal cortex. AR antagonism with enzalutamide attenuated corticosterone-induced expression of Fkbp5 in the prefrontal cortex and of Fkbp5 and Sgk1 in the substantia nigra. Additionally, in the substantia nigra, AR antagonism increased expression of Th and Slc18a1, two genes coding for key components of the dopaminergic system. Our data indicate that androgen influence over glucocorticoid stimulation in the brain is not a dominant phenomenon in the context of high corticosterone levels, but can occur in the prefrontal cortex and substantia nigra.

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Section: Discussionsupporting

confidence: 93%

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain

Amaya,

Sips,

Viho

et al. 2024

Front. Endocrinol.

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“…Additionally, it may illuminate the mechanisms underlying general differences between men and women with schizophrenia ( 140 ). Further, computational methods may highlight specific aspects of psychosis that estrogen alone cannot explain, thereby facilitating targeted research into how other hormones, such as androgens ( 141 , 142 ) and neurosteroids ( 143 ), affect psychosis. This proposed multifaceted approach may be crucial to improving our understanding of psychosis and orienting future research.…”

Section: Discussion and Guidance For Future Directionsmentioning

confidence: 99%

A computational lens on menopause-associated psychosis

2022

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Psychotic episodes are debilitating disease states that can cause extreme distress and impair functioning. There are sex differences that drive the onset of these episodes. One difference is that, in addition to a risk period in adolescence and early adulthood, women approaching the menopause transition experience a second period of risk for new-onset psychosis. One leading hypothesis explaining this menopause-associated psychosis (MAP) is that estrogen decline in menopause removes a protective factor against processes that contribute to psychotic symptoms. However, the neural mechanisms connecting estrogen decline to these symptoms are still not well understood. Using the tools of computational psychiatry, links have been proposed between symptom presentation and potential algorithmic and biological correlates. These models connect changes in signaling with symptom formation by evaluating changes in information processing that are not easily observable (latent states). In this manuscript, we contextualize the observed effects of estrogen (decline) on neural pathways implicated in psychosis. We then propose how estrogen could drive changes in latent states giving rise to cognitive and psychotic symptoms associated with psychosis. Using computational frameworks to inform research in MAP may provide a systematic method for identifying patient-specific pathways driving symptoms and simultaneously refine models describing the pathogenesis of psychosis across all age groups.

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Sex Differences in Psychosis: Focus on Animal Models

Gogos

Buuse

2022

Sex Differences in Brain Function and Dysfunction

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Effect of adolescent androgen manipulation on psychosis-like behaviour in adulthood in BDNF heterozygous and control mice

Cited by 4 publications

References 72 publications

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain

A computational lens on menopause-associated psychosis

Sex Differences in Psychosis: Focus on Animal Models

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