Parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons show histological abnormalities in individuals with schizophrenia and are hypothesized to regulate oscillatory synchrony within the prefrontal cortex.
Over 800 transcripts in PV neurons were identified as differentially expressed in SZ subjects; most of these alterations have not previously been reported.
These results provide the first evidence that PVALB promoter methylation is abnormal in schizophrenia and suggest that this epigenetic finding may relate to the reduction of PV expression seen in the disease.
The decrease in density of parvalbumin-positive neurons in schizophrenia, one of the most replicated findings in the field, is used to illustrate features of the brain bank.
Hypofunction of NMDA receptors in parvalbumin (PV)-positive interneurons has been proposed as a potential mechanism for cortical abnormalities and symptoms in schizophrenia.
Furthermore, we found that many of the genes previously identified as differentially expressed in schizophrenia are highly correlated with the expression profiles of astrocytes or fast-spiking parvalbumin interneurons.
Given the role of PV-containing fast-spiking basket cells in generation of oscillations and the decreased PV expression in subjects with schizophrenia, the study of gamma oscillations in organotypic hippocampal slices represents a potentially valuable tool for the characterization of novel therapeutic drugs.
Levels of ErbB4 splice variants and PV mRNA were quantified by PCR in the DLPFC from 40 matched tetrads (N = 160 subjects) of schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), and unaffected comparison subjects.
Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors.
For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia.
Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol rodent model of schizophrenia.
Although these phenotypic influences on GABA neurons became less marked during development, it later resulted in the reduced β- and γ-powers of sound-evoked electroencephalogram in adults, which is regulated by parvalbumin-positive GABA neurons and implicated in the schizophrenia pathophysiology.
Alterations in parvalbumin interneurons (PV neurons) and perineuronal nets (PNNs) within the PFC have been implicated in schizophrenia and autism spectrum disorder pathology.
Decreased labeling of perineuronal nets, a form of ECM predominantly associated with parvalbumin-expressing interneurons in the brain, has been observed in post-mortem studies of schizophrenia patients, specifically, in brain areas such as prefrontal cortex, entorhinal cortex, and amygdala.
The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration.
Post-mortem analyses have demonstrated a selective reduction in the expression of parvalbumin (PV) in GABAergic interneurons in the frontal rather than the sensory cortex of patients with neuropsychiatric disorders such as schizophrenia, autism spectrum disorders, and bipolar disorders.
Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition.
N-methyl-D-aspartate receptor (NMDAR) hypofunction in parvalbumin-expressing (PV+) inhibitory neurons (INs) may contribute to symptoms in patients with schizophrenia (SZ).
Substantial evidence suggests that abnormalities in inhibitory γ-aminobutyric acid (GABA) interneuron function, especially in the parvalbumin subtype of GABA interneuron, both developmentally and in adulthood, may contribute mechanistically to cognitive deficits and psychotic symptoms in schizophrenia.
Therefore, the authors hypothesized that dysregulated ErbB4 splicing occurs selectively in parvalbumin interneurons and is associated with lower parvalbumin levels in schizophrenia.
Taken together, findings of this study provide a neurobiological framework within which hypotheses of the molecular mechanisms that underlie the dysfunction of PV neurons in schizophrenia can be generated and experimentally explored and, as such, may ultimately inform the conceptualization of rational targeted molecular intervention for this debilitating disorder.