Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias

Separating the effects of ethnicity and socio-economic status on sleep practices of 6- to 7-month-old infants

Infant sleep undergoes significant re-organization throughout the first 12 months of life, with sleep quality having significant consequences for infant learning and cognitive development. While there has been great interest in the neural basis and developmental trajectories of infant sleep in general, relatively little is known about individual differences in infant sleep and the socio-economic and cultural sources of that variability. We investigated this using questionnaire sleep data in a large, unique multi-ethnic sample of 6-7 month-olds (n=174), with families from South Asian ethnic groups in the UK (Indian, Pakistani and Bangladeshi) being especially well represented. Consistent with previous data from less variable samples, no effects of SES on sleep latency or nocturnal sleep duration emerged. However, perinatal risk factors and ethnic differences did predict daytime sleep, sleep fragmentation and sleep-onset time. While these results should be interpreted with caution due to several limitations, they likely demonstrate that even when socio-economic status and ethnicity are much less confounded than in previous studies, they have a surprisingly limited impact on individual differences in sleep patterns in young infants.