Emerging evidence for astrocyte dysfunction in schizophrenia.

Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, and whose precise etiology is still poorly understood. Schizophrenia is not characterized by gross brain pathology, but involves subtle pathological changes in neuronal populations and glial cells. Among the latter, astrocytes critically contribute to the regulation of early neurodevelopmental processes, and any dysfunctions in their morphological and functional maturation may lead to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia, such as mitochondrial biogenesis, synaptogenesis, and glutamatergic and dopaminergic transmission. Studies of the mechanisms regulating astrocyte maturation may therefore improve our understanding of the cellular and molecular mechanisms underlying the pathogenesis of schizophrenia.

Synaptic Plasticity Dysfunctions in the Pathophysiology of 22q11 Deletion Syndrome: Is There a Role for Astrocytes?

The 22q11 deletion syndrome (DS) is the most common microdeletion syndrome in humans and gives a high probability of developing psychiatric disorders. Synaptic and neuronal malfunctions appear to be at the core of the symptoms presented by patients. In fact, it has long been suggested that the behavioural and cognitive impairments observed in 22q11DS are probably due to alterations in the mechanisms regulating synaptic function and plasticity. Often, synaptic changes are related to structural and functional changes observed in patients with cognitive dysfunctions, therefore suggesting that synaptic plasticity has a crucial role in the pathophysiology of the syndrome. Most interestingly, among the genes deleted in 22q11DS, six encode for mitochondrial proteins that, in mouse models, are highly expressed just after birth, when active synaptogenesis occurs, therefore indicating that mitochondrial processes are strictly related to synapse formation and maintenance of a correct synaptic signalling. Because correct synaptic functioning, not only requires correct neuronal function and metabolism, but also needs the active contribution of astrocytes, we summarize in this review recent studies showing the involvement of synaptic plasticity in the pathophysiology of 22q11DS and we discuss the relevance of mitochondria in these processes and the possible involvement of astrocytes.