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Review
. 2024 Aug 9;25(16):8696.
doi: 10.3390/ijms25168696.

Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators

Masaya Yanagi  1 , Mamoru Hashimoto  1
Affiliations
Review

Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators

Masaya Yanagi et al. Int J Mol Sci. .

Abstract

Based on the pathophysiological changes observed in schizophrenia, the gamma-aminobutyric acid (GABA) hypothesis may facilitate the development of targeted treatments for this disease. This hypothesis, mainly derived from postmortem brain results, postulates dysfunctions in a subset of GABAergic neurons, particularly parvalbumin-containing interneurons. In the cerebral cortex, the fast spike firing of parvalbumin-positive GABAergic interneurons is regulated by the Kv3.1 and Kv3.2 channels, which belong to a potassium channel subfamily. Decreased Kv3.1 levels have been observed in the prefrontal cortex of patients with schizophrenia, prompting the investigation of Kv3 channel modulators for the treatment of schizophrenia. However, biomarkers that capture the dysfunction of parvalbumin neurons are required for these modulators to be effective in the pharmacotherapy of schizophrenia. Electroencephalography and magnetoencephalography studies have demonstrated impairments in evoked gamma oscillations in patients with schizophrenia, which may reflect the dysfunction of cortical parvalbumin neurons. This review summarizes these topics and provides an overview of how the development of therapeutics that incorporate biomarkers could innovate the treatment of schizophrenia and potentially change the targets of pharmacotherapy.

Keywords: GABA; Kv3; parvalbumin; schizophrenia; targeted therapeutics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
A possible targeted treatment of Kv3 modulator. This figure demonstrates that a Kv3.1 modulator is a promising treatment for schizophrenia in future clinical settings. The auditory steady-state response (ASSR) can help identify patients with significant evoked gamma oscillation impairments. The novel modulator for Kv3.1, the voltage-gated potassium channel that regulates the firing in parvalbumin-positive GABAergic interneurons, may be effective for patients with schizophrenia who were stratified by ASSR impairments. This systematic strategy may pave the way for targeted therapeutics in psychiatry.
See this image and copyright information in PMC

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