INTRODUCTION
Depression is a multifactorial disorder with significant global health impact. Neuroimaging advances have provided insights into neural mechanisms underlying depression, while gut microbiome alterations have been linked to brain structure and function. This review summarizes evidence on the association between gut microbiome variability and brain structural and functional changes in Major Depressive Disorder (MDD) and Bipolar Depression (BD).
METHODS
A bibliographic search was conducted on PubMed, Scopus and Web of Science for original studies investigating correlations between gut microbiome and brain structure and function.
RESULTS
Three studies investigated probiotic interventions in MDD, showing significant associations with increased gray matter volume (GMV) in the calcarine sulcus, reduced putamen and hippocampal activation, and altered fronto-limbic functional connectivity, especially within the precuneus and superior parietal lobule. Also, observational studies in MDD showed that specific microbial taxa or alpha diversity were positively correlated with limbic and basal ganglia GMV, whereas other taxa negatively correlated with frontal connectivity or GMV in regions involved in memory, somatosensory integration, and emotional regulation. Finally, although no interventional studies were available for BD, the available observational studies in this disorder exhibited gut-brain imbalance associations with immune activation and prefrontal dysfunction, with gut microbes linked to neuroactive metabolites correlated with altered connectivity in thalamus, striatum, and language and limbic regions.
CONCLUSIONS
From the available literature emerged that gut microbiome variations seem to be associated with brain structural and functional alterations in both MDD and BD, with preliminary evidence also suggesting significant neurobiological effects of probiotics in MDD. Nonetheless, further studies are needed to confirm the role of gut microbiome modulation as part of personalized approaches.
Federico Bottaro, P. Enrico, C. Cabasino et al.· Journal of Affective Disorde...· 0 citations
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by loss-of-function mutations in the MECP2 gene and characterized by profound impairments in neuronal maturation and synaptic connectivity. Increasing evidence indicates that astrocyte dysfunction contributes to RTT pathogenesis through non-cell-autonomous mechanisms, although the molecular pathways underlying defective astrocyte-neuron communication are only partially understood. Astrocytes are the primary source of cholesterol in the brain and support neuronal maturation and synaptic function by supplying cholesterol through ApoE-containing lipoproteins. Although alterations in brain cholesterol metabolism have been reported in RTT, the underlying cellular mechanisms and their functional consequences remain poorly investigated. Here, we studied cholesterol homeostasis in Mecp2 knock-out (KO) astrocytes and its impact on neuron-astrocyte communication. Mecp2 KO astrocytes exhibited reduced nuclear localization of the transcriptional regulator Srebp2, together with the downregulation of genes involved in cholesterol biosynthesis and transport. These molecular alterations were associated with intracellular cholesterol and desmosterol accumulation, reduced Abca1 expression and defective ApoE lipidation, despite preserved ApoE expression and cholesterol secretion. Importantly, similar alterations were detected in acutely isolated astrocytes and in the cerebral cortex of Mecp2 deficient mice, demonstrating that impaired cholesterol homeostasis extends beyond in vitro models. Functionally, cholesterol supplementation of astrocyte-conditioned medium rescued the synaptic defects induced in wild-type neurons by Mecp2 KO astrocytes. Moreover, cholesterol treatment restored pre- and post-synaptic density, as well as axon initial segment length in Mecp2 heterozygous (HET) neurons. Together, these findings identify defective astrocyte-to- neuron cholesterol trafficking as a key mechanism contributing to neuronal dysfunction in RTT and suggest that strategies aimed at restoring cholesterol functional availability might represent a promising therapeutic avenue for RTT.
Francesca M. Postogna, Noemi Giancroce, C. Cabasino et al.· bioRxiv· 0 citations