Abstract
BackgroundAlterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients.ResultsWe have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis.ConclusionsThe present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis.
Highlights
Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders
We investigated whether the densities of PV expressing interneurons and perineuronal nets (PNNs) were affected in the dorsolateral PFC (DLPFC) of individuals suffering from major depression, schizophrenia or bipolar disorder
Samples and histological processing Frozen 14 μm thick coronal sections containing the dorsolateral prefrontal cortex (DLPFC) of patients diagnosed with major depression, bipolar disorder or schizophrenia, and control subjects were obtained from the Stanley
Summary
Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. PV expressing interneurons effectively synchronize large populations of neurons, regulating the synaptic excitatory tone in different cortical regions (Hu et al 2014). Alterations in this subpopulation of interneurons have been described in different psychiatric diseases, such as major depression, schizophrenia, autism or bipolar disorder (Marín 2012). Anomalies in PV expressing interneurons have been reported in animal models of major depression (Perova et al 2015; Pesarico et al 2019; Sauer et al 2015; Todorovic et al 2019)
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