Gene expression profile associated with postnatal development of pyramidal neurons in the human prefrontal cortex implicates ubiquitin ligase E3 in the pathophysiology of schizophrenia onset.

Schizophrenia is a neurodevelopmental disorder with the typical age of onset of overt symptoms and deficits occurring during late adolescence or early adulthood, coinciding with the final maturation of the cortical network involving the prefrontal cortex. These observations have led to the hypothesis that disturbances of the developmental events that take place in the prefrontal cortex during this period, specifically the remodeling of synaptic connectivities between pyramidal neurons, may contribute to the onset of illness. In this context, we investigated the gene expression changes of pyramidal neurons in the human prefrontal cortex during normal periadolescent development in order to gain insight into the possible molecular mechanisms involved in synaptic remodeling of pyramidal neuronal circuitry.

Differentiation of oligodendrocyte precursors is impaired in the prefrontal cortex in schizophrenia.

The pathophysiology of schizophrenia involves disturbances of information processing across brain regions, possibly reflecting, at least in part, a disruption in the underlying axonal connectivity. This disruption is thought to be a consequence of the pathology of myelin ensheathment, the integrity of which is tightly regulated by oligodendrocytes. In order to gain insight into the possible neurobiological mechanisms of myelin deficit, we determined the messenger RNA (mRNA) expression profile of laser captured cells that were immunoreactive for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), a marker for oligodendrocyte progenitor cells (OPCs) in addition to differentiating and myelinating oligodendrocytes, in the white matter of the prefrontal cortex in schizophrenia subjects.

Molecular profiles of pyramidal neurons in the superior temporal cortex in schizophrenia.

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30-100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia.

Molecular profiles of parvalbumin-immunoreactive neurons in the superior temporal cortex in schizophrenia.

Dysregulation of pyramidal cell network function by the soma- and axon-targeting inhibitory neurons that contain the calcium-binding protein parvalbumin (PV) represents a core pathophysiological feature of schizophrenia. In order to gain insight into the molecular basis of their functional impairment, we used laser capture microdissection (LCM) to isolate PV-immunolabeled neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem schizophrenia and normal control brains. We then extracted ribonucleic acid (RNA) from these neurons and determined their messenger RNA (mRNA) expression profile using the Affymetrix platform of microarray technology.

Comparison of brain and blood gene expression in an animal model of negative symptoms in schizophrenia.

Objectives: To investigate the potential of white blood cells as probes for central processes we have measured gene expression in both the anterior cingulate cortex and white blood cells using a putative animal model of negative symptoms in schizophrenia.

Methods: The model is based on the capability of ketamine to induce psychotic symptoms in healthy volunteers and to worsen such symptoms in schizophrenic patients. Classical fear conditioning is used to assess emotional processing and cognitive function in animals exposed to sub-chronic ketamine vs.

Neuronal type-specific gene expression profiling and laser-capture microdissection.

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling.

Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: role of serotonin synthesis.

We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function, and attempted to identify underlying mechanisms. Biochemistry of serotonin was assessed with brain tissue assays and microdialysis; behavior was assessed as the acoustic startle reflex. Long-term SSRI administration to rats reduced the content of 5-HT and its main metabolite shortly after inhibition of 5-HT synthesis in many brain areas with more than 50%.

Obtaining high quality RNA from single cell populations in human postmortem brain tissue.

We proposed to investigate the gray matter reduction in the superior temporal gyrus seen in schizophrenia patients, by interrogating gene expression profiles of pyramidal neurons in layer III. It is well known that the cerebral cortex is an exceptionally heterogeneous structure comprising diverse regions, layers and cell types, each of which is characterized by distinct cellular and molecular compositions and therefore differential gene expression profiles. To circumvent the confounding effects of tissue heterogeneity, we used laser-capture microdissection (LCM) in order to isolate our specific cell-type i.

An animal model of emotional blunting in schizophrenia.

Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia.

Ketamine administration disturbs behavioural and distributed neural correlates of fear conditioning in the rat.

The neurotransmitter glutamate and its associated receptors perform an important role in the brain circuitry underlying normal fear processing. The glutamate NMDA receptor, in particular, is necessary for the acquisition and recollection of conditioned-fear responses. Here the authors examine how acute blockage of the NMDA receptor with sub-anaesthetic doses of ketamine affects behavioural assays of fear-conditioned stress (e.