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. 2019 Nov 15;7(1):24.
doi: 10.1186/s40345-019-0161-0.

Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients

Julia Alcaide  1 , Ramón Guirado  1 , Carlos Crespo  1 , José Miguel Blasco-Ibáñez  1 , Emilio Varea  1 , Julio Sanjuan  2   3   4 , Juan Nacher  5   6   7
Affiliations

Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients

Julia Alcaide et al. Int J Bipolar Disord. .

Abstract

Background: Alterations 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.

Results: We 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.

Conclusions: The 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.

Keywords: Bipolar disorder; Major depression; Parvalbumin; Perineuronal nets; Prefrontal cortex; Schizophrenia.

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Conflict of interest statement

All authors disclose any actual or potential competing interest including any financial, personal or other relationships with other people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, this work.

Figures

Fig. 1
Fig. 1
Alterations of PV and PNN densities in neuropsychiatric disorders. a Panoramic confocal microphotograph showing WFA-labeled PNNs (blue) surrounding PV positive somata (red) in the deep layers of the dorsolateral prefrontal cortex (DLPFC) of a control individual. b Images of single confocal planes showing PNNs surrounding PV+ somata in the DLPFC in patients suffering from major depression (MD), bipolar disorder (BD) and schizophrenia (SCHZ) and controls (NOR). White arrowheads point to PV+ somata surrounded by PNNs, yellow arrowheads point to PV+ cells lacking PNNs and white arrows point to PNNs surrounding PV− somata. c–g Histograms showing the density of PV expressing interneurons (c), PNNs (d) and the percentages of PV expressing somata surrounded by PNNs (e), of PNNs surrounding PV+ somata (f) and of PNNs not surrounding PV+ somata (g). There are significant differences in the density of PNN between control individuals and bipolar patients (*p = 0.012). Scale bar: 20 µm
Fig. 2
Fig. 2
Effects of psychosis on the density of PNNs. a Confocal images, showing WFA-labeled PNNs (blue) surrounding PV positive somata (red) in the dorsolateral prefrontal cortex (DLPFC) of patients diagnosed with (a2) and without (a1) psychosis. b Histogram comparing the density of PNNs in individuals diagnosed with (black bar) or without (white bar) psychosis (Pr(> F) = 0.034; Pr(> |t|) = 0.035). Scale bar: 20 µm
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References

    1. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, Jr, et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry. 1995;52(4):258–266. doi: 10.1001/archpsyc.1995.03950160008002. - DOI - PubMed
    1. Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al. Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord. 2008;111(2–3):135–144. doi: 10.1016/j.jad.2008.04.013. - DOI - PubMed
    1. Balmer TS. Perineuronal Nets Enhance the Excitability of Fast-Spiking Neurons. eNeuro. 2016 doi: 10.1523/ENEURO.0112-16.2016. - DOI - PMC - PubMed
    1. Beasley C, Reynolds G. Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res. 1997;24(3):349–355. doi: 10.1016/S0920-9964(96)00122-3. - DOI - PubMed
    1. Beasley CL, Zhang ZJ, Patten I, Reynolds GP. Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins. Biol Psychiatry. 2002;52(7):708–715. doi: 10.1016/S0006-3223(02)01360-4. - DOI - PubMed

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