Insights into myelin dysfunction in schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.

Potential Use of Exfoliated and Cultured Olfactory Neuronal Precursors for In Vivo Alzheimer's Disease Diagnosis: A Pilot Study.

Histopathological hallmarks of dementia have been described postmortem in the brain of patients with Alzheimer's disease (AD). Tau, a microtubule associated protein, is abnormally arranged in neurofibrillary tangles. In living AD patients, total tau (t-tau) and hyperphosphorylated tau (p-tau) levels are increased in the cerebrospinal fluid obtained by lumbar puncture. Herein, we studied the t-tau and p-tau levels as well as the subcellular distribution of t-tau in olfactory neuronal precursors obtained by exfoliation of the nasal cavity of AD patients and control participants. Data showed that t-tau and p-tau levels were increased in cell homogenates from AD patients. Also, t-tau immunoreactivity was arranged in a punctate pattern in olfactory neuronal precursors derived from an AD participant with 5 years of evolution and in the oldest participants, either control subjects or those with Alzheimer's disease. Results support that exfoliated neuronal precursors have tau alterations demonstrated in postmortem brain and in the cerebrospinal fluid. This evidence and because the obtainment of olfactory neuronal precursors is a noninvasive procedure, detection of tau alterations shown here might be useful for an early diagnosis of AD-type dementia.