ArticleCNS neuroscience & therapeutics2026
Effects of the STriatal Enriched Tyrosine Phosphatase (STEP) Inhibitor TC-2153 on Hippocampal Long-Term Depression and Synaptic Transmission: Paradoxical Effect on Phosphatase Activity and Role of Adenosine.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsThis study aimed to explore the effects of TC-2153, the STriatal Enriched Tyrosine Phosphatase (STEP) inhibitor, on Long-Term Depression (LTD) and basal synaptic transmission in hippocampal slices.
methodsExtracellular field potentials were recorded in the CA1 area of the hippocampal slices. LTD was induced by low-frequency stimulation and by metabotropic glutamate receptor stimulation. The activity of STEP was measured in hippocampal slices and in SH-SY5Y cell culture by a colorimetric assay using p-nitrophenol as a substrate. To evaluate adenosine levels, adenosine was extracted from hippocampal slices homogenates and measured by HPLC.
resultsTC-2153 3 μM, applied to the slices one hour before and then along the electrophysiological recordings, blocked both forms of LTD. When hippocampal slices were treated with TC-2153 for shorter periods, 10-20 min, TC-2153 reduced synaptic transmission and increased STEP activity with an adenosine A1 receptor-dependent mechanism. Consistently, we found that TC-2153 increased adenosine levels in hippocampal slices. The increase in STEP activity after brief TC-2153 treatment has been confirmed in SH-SY5Y cells.
conclusionOur study confirms the role of STEP in LTD and reveals a new mechanism of action for TC-2153. The unexpected adenosine-dependent activation of STEP by TC-2153 has significant implications for both basic research and potential therapeutic applications.
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