Targeting neuronal nitric oxide synthase and the nitrergic system in post-traumatic stress disorder

Sadeghi, Maryam; Hemmati, Sara; Nassireslami, Ehsan; Zoshk, Mojtaba Yousefi; Hosseini, Yasaman; Abbasian, Kourosh; Chamanara, Mohsen

doi:10.1007/s00213-022-06212-7

Cited by 10 publications

(2 citation statements)

References 126 publications

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“…These results suggest that both NOS-1 and NOS-2 participate in the production of NO in time-dependent sensitization, but at different time intervals. In the single-prolonged stress model, conditional knockout of NOS-1 in the dorsal raphe nucleus of mice rescues the PTSD-like phenotype (increased anxiety-like behavior, enhanced contextual fear memory, and fear generalization) (Sadeghi et al, 2022). A participation of NOS isozymes in the behavioral effects of TDS was demonstrated in zebrafish, in which treatment with the non-selective inhibitor L-NAME 30 and 90 min.…”

Section: Introductionmentioning

confidence: 99%

Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish

de Sousa,

Heymbeeck,

Feitosa

et al. 2024

Preprint

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Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in time-dependent sensitization, a behavioral model of translational relevance to trauma and stress-related disorders, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents TDS; blocking NOS-2 90 min after stress also prevents TDS, as does blocking calcium-activated potassium channels in this latter time window. TDS is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce TDS.

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Section: Introductionmentioning

confidence: 99%

Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish

de Sousa,

Heymbeeck,

Feitosa

et al. 2024

Preprint

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show abstract

“…One of the questions that motivate this review is to identify if nNOS underlying pathways exert a significant role in response to trauma and in the pathophysiology of fear-related disorders. NO is a gaseous neuromodulator that regulates, among several other functions, neuronal function, particularly related to learning and memory [9], and fear-related and defensive responses [10]; it thereby plays an important role in related psychiatric disorders [11], including in PTSD [12]. For example, polymorphisms on NO pathway genes, NOS1 (nNOS) and its adaptor protein NOS1AP are involved in PTSD severity, depression, anxiety, stress, and resilience [13][14][15], which strongly suggest its involvement in the pathophysiology of this disorder.…”

Section: Introductionmentioning

confidence: 99%

“NO” Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD

Fronza,

Ferreira,

Pavan-Silva

et al. 2023

Molecules

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Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by persistent fear responses and altered neurotransmitter functioning due to traumatic experiences. Stress predominantly affects glutamate, a neurotransmitter crucial for synaptic plasticity and memory formation. Activation of the N-Methyl-D-Aspartate glutamate receptors (NMDAR) can trigger the formation of a complex comprising postsynaptic density protein-95 (PSD95), the neuronal nitric oxide synthase (nNOS), and its adaptor protein (NOS1AP). This complex is pivotal in activating nNOS and nitric oxide (NO) production, which, in turn, activates downstream pathways that modulate neuronal signaling, including synaptic plasticity/transmission, inflammation, and cell death. The involvement of nNOS and NOS1AP in the susceptibility of PTSD and its comorbidities has been widely shown. Therefore, understanding the interplay between stress, fear, and NO is essential for comprehending the maintenance and progression of PTSD, since NO is involved in fear acquisition and extinction processes. Moreover, NO induces post-translational modifications (PTMs), including S-nitrosylation and nitration, which alter protein function and structure for intracellular signaling. Although evidence suggests that NO influences synaptic plasticity and memory processing, the specific role of PTMs in the pathophysiology of PTSD remains unclear. This review highlights pathways modulated by NO that could be relevant to stress and PTSD.

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Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine’s anxiogenic activity in an animal model of PTSD

Sadeghi

Hemmati²,

Yousefi‐Manesh³

et al. 2023

Behavioural Brain Research

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Targeting neuronal nitric oxide synthase and the nitrergic system in post-traumatic stress disorder

Cited by 10 publications

References 126 publications

Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish

Role of the NOS-cGMP pathways in time-dependent sensitization of behavioral responses in zebrafish

“NO” Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD

Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine’s anxiogenic activity in an animal model of PTSD

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