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<p>Although tumor necrosis factor-alpha (TNF-α) plays an important role in the development of obsessive–compulsive disorder (OCD), the pathogenesis remains unclear. Since transient receptor potential melastatin 3 (TRPM3) channels are activated during inflammatory conditions, crosstalk with TNF-α in the progression of OCD has not been investigated yet. We hypothesize that mild traumatic brain injury (mTBI) stimulates TRPM3 channels, thereby enhancing the level of TNF-α in the medial prefrontal cortex (mPFC), a key brain region implicated in OCD pathogenesis. The closed-head weight-drop method was used for mTBI-induced OCD in mice, and neurological assessment was carried out using rotarod and beam-walk tests. Marble-burying test, open-field test, dark–light emergence test, and nest-building behavior test were performed to examine OCD-like symptoms. The mPFC was isolated, and the TNF-α level and TRPM3 immunoreactivity were estimated using ELISA and immunohistochemistry techniques. Additionally, Golgi–Cox staining and HPLC were performed to quantify dendritic arbor and serotonin content. To validate our hypothesis, mTBI mice were treated with a selective&#xa0;TRPM3 inhibitor naringenin (50&#xa0;mg/kg) via intraperitoneal route, and all the above parameters were screened. Marble-burying and nest-building behaviors were increased in mTBI mice. However, exploratory behavior and time spend in the light chamber were significantly reduced. Moreover, mTBI increases TNF-α concentration and TRPM3 immunoreactivity, while decreasing dendritic arbor and serotonin content. Notably, naringenin treatment reversed these behavioral, biochemical, and molecular abnormalities. Naringenin may inhibit TRPM3-mediated TNF-α production and serotonin transmission, thereby suppressing OCD symptoms. Thus, we propose a novel therapeutic approach for treating OCD associated with traumatic brain injury.</p>

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Inhibition of TRPM3 channels in the medial prefrontal cortex mitigates OCD symptoms following traumatic brain injury

  • 期刊论文

  • 发表日期：

    2025年5月15日

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  • Gajendra N. Pardeshi,
  • Noor Ali,
  • Kamini R. Shirasath,
  • Sameer N. Goyal,
  • Kartik T. Nakhate,
  • Sanjay N. Awathale

摘要

Although tumor necrosis factor-alpha (TNF-α) plays an important role in the development of obsessive–compulsive disorder (OCD), the pathogenesis remains unclear. Since transient receptor potential melastatin 3 (TRPM3) channels are activated during inflammatory conditions, crosstalk with TNF-α in the progression of OCD has not been investigated yet. We hypothesize that mild traumatic brain injury (mTBI) stimulates TRPM3 channels, thereby enhancing the level of TNF-α in the medial prefrontal cortex (mPFC), a key brain region implicated in OCD pathogenesis. The closed-head weight-drop method was used for mTBI-induced OCD in mice, and neurological assessment was carried out using rotarod and beam-walk tests. Marble-burying test, open-field test, dark–light emergence test, and nest-building behavior test were performed to examine OCD-like symptoms. The mPFC was isolated, and the TNF-α level and TRPM3 immunoreactivity were estimated using ELISA and immunohistochemistry techniques. Additionally, Golgi–Cox staining and HPLC were performed to quantify dendritic arbor and serotonin content. To validate our hypothesis, mTBI mice were treated with a selective TRPM3 inhibitor naringenin (50 mg/kg) via intraperitoneal route, and all the above parameters were screened. Marble-burying and nest-building behaviors were increased in mTBI mice. However, exploratory behavior and time spend in the light chamber were significantly reduced. Moreover, mTBI increases TNF-α concentration and TRPM3 immunoreactivity, while decreasing dendritic arbor and serotonin content. Notably, naringenin treatment reversed these behavioral, biochemical, and molecular abnormalities. Naringenin may inhibit TRPM3-mediated TNF-α production and serotonin transmission, thereby suppressing OCD symptoms. Thus, we propose a novel therapeutic approach for treating OCD associated with traumatic brain injury.