Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors

Abdelhamid, Ramy E.; Kovács, Katalin; Nunez, Myra G.; Larson, Alice A.

doi:10.1016/j.phrs.2013.10.006

Cited by 56 publications

(25 citation statements)

References 65 publications

(78 reference statements)

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“…Activation of TRPV1 by differential ligands or in differential conditions (physiological or pathological) might exert distinct effects on NMDA receptors. This is accordance with the reports that both TRPV1 agonists and antagonists show the antidepressant effects partly through the inhibition of NMDA receptors (Abdelhamid et al, 2014; Amiri et al, 2016; Manna and Umathe, 2012; Sartim et al, 2017). …”

Section: Discussionsupporting

confidence: 93%

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

Huang

Cheng

Tan

et al. 2017

Experimental Neurology

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Capsaicin, the ingredient responsible for the pungent taste of hot chili peppers, is widely used in the study and management of pain. Recently, its neuroprotective effect has been described in multiple studies. Herein, we investigated the underlying mechanisms for the neuroprotective effect of capsaicin. Direct injection of capsaicin (1 or 3 nmol) into the peri-infarct area reduced the infarct volume and improved neurological behavioral scoring and motor coordination function in the middle cerebral artery occlusion (MCAO)/reperfusion model in rats. The time window of the protective effect of capsaicin was within 1 h after reperfusion, when excitotoxicity is the main reason of cell death. In cultured cortical neurons, administration of capsaicin attenuated glutamate-induced excitotoxic injury. With respect to the mechanisms of the neuroprotective effect of capsaicin, reduced calcium influx after glutamate stimulation was observed following capsaicin pretreatment in cortical neurons. Trpv1 knockout abolished the inhibitory effect of capsaicin on glutamate-induced calcium influx and subsequent neuronal death. Reduced expression of GluN1 and GluN2B, subunits of NMDA receptor, was examined after capsaicin treatment in cortical neurons. In summary, our studies reveal that the neuroprotective effect of capsaicin in cortical neurons is TRPV1-dependent and down-regulation of the expression and function of NMDA receptors contributes to the protection afforded by capsaicin.

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Section: Discussionsupporting

confidence: 93%

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

Huang

Cheng

Tan

et al. 2017

Experimental Neurology

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“…When the mice are tested again 24 h later, floating times are immediately increased, consistent with the previously reported potentiative effect of conditioning swim on immobility [29]. Fifteen-min conditioning swims on day one are frequently used [26-29] and we previously reported depressive-like behavioral data using that experimental design [24]. …”

Section: Methodssupporting

confidence: 84%

After a cold conditioning swim, UCP2-deficient mice are more able to defend against the cold than wild type mice

Abdelhamid

Kovács

Nunez

et al. 2014

Physiology & Behavior

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Uncoupling protein 2 (UCP2) is widely distributed throughout the body including the brain, adipose tissue and skeletal muscles. In contrast to UCP1, UCP2 does not influence resting body temperature and UCP2-deficient (-/-) mice have normal thermoregulatory responses to a single exposure to cold ambient temperatures. Instead, UCP2-deficient mice are more anxious, exhibit anhedonia and have higher circulating corticosterone than wild type mice. To test the possible role of UCP2 in depressive behavior we exposed UCP2-deficient and wild type mice to a cold (26°C) forced swim and simultaneously measured rectal temperatures during and after the swim. The time that UCP2-deficient mice spent immobile did not differ from wild type mice and all mice floated more on day 2. However, UCP2-deficient mice were more able to defend against the decrease in body temperature during a second daily swim at 26°C than wild type mice (area under the curve for wild type mice: 247.0 ± 6.4; for UCP2-deficient mice: 284.4 ± 3.8, P<0.0001, Student's t test). The improved thermoregulation of wild type mice during a second swim at 26°C correlated with their greater immobility whereas defense against the warmth during a swim at 41°C correlated better with greater immobility of UCP2-deficient mice. Together these data indicate that while the lack of UCP2 has no acute effect on body temperature, UCP2 may inhibit rapid improvements in defense against cold, in contrast to UCP1, whose main function is to promote thermogenesis.

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“…AD + AAV EGFP ; Figure d). Besides learning and memory deficits, patients with AD are often accompanied by depression, and laboratory research has shown that TRPV1 activation may affect anxiogenic responses and depression‐related behaviors (Abdelhamid, Kovacs, Nunez, & Larson, ; Kasckow, Mulchahey, & Geracioti, ). We here further found that TRPV1 upregulation by AAV TRPV1 could significantly ameliorate anxiety‐ and depression‐like behaviors in APP23/PS45 mice during the elevated plus maze (Figure a and b), three‐chambered social interaction (Figure c), and force swimming tests (Figure d).…”

Section: Resultsmentioning

confidence: 99%

TRPV1 activation alleviates cognitive and synaptic plasticity impairments through inhibiting AMPAR endocytosis in APP23/PS45 mouse model of Alzheimer’s disease

Huang

et al. 2020

Aging Cell

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Alzheimer's disease (AD) is one of the most common causes of neurodegenerative diseases in the elderly. The accumulation of amyloid‐β (Aβ) peptides is one of the pathological hallmarks of AD and leads to the impairments of synaptic plasticity and cognitive function. The transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel, is involved in synaptic plasticity and memory. However, the role of TRPV1 in AD pathogenesis remains largely elusive. Here, we reported that the expression of TRPV1 was decreased in the brain of APP23/PS45 double transgenic AD model mice. Genetic upregulation of TRPV1 by adeno‐associated virus (AAV) inhibited the APP processing and Aβ deposition in AD model mice. Meanwhile, upregulation of TRPV1 ameliorated the deficits of hippocampal CA1 long‐term potentiation (LTP) and spatial learning and memory through inhibiting GluA2‐containing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) endocytosis. Furthermore, pharmacological activation of TRPV1 by capsaicin (1 mg/kg, i.p.), an agonist of TRPV1, dramatically reversed the impairments of hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, these results indicate that TRPV1 activation effectively ameliorates cognitive and synaptic functions through inhibiting AMPAR endocytosis in AD model mice and could be a novel molecule for AD treatment.

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Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors

Cited by 56 publications

References 65 publications

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

After a cold conditioning swim, UCP2-deficient mice are more able to defend against the cold than wild type mice

TRPV1 activation alleviates cognitive and synaptic plasticity impairments through inhibiting AMPAR endocytosis in APP23/PS45 mouse model of Alzheimer’s disease

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