Oxytocin and Neuroprotective Effects

Erbaş, Oytun; Altuntaş, İlknur

doi:10.5772/intechopen.96527

Cited by 4 publications

(3 citation statements)

References 101 publications

(125 reference statements)

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“…The potential clinical usefulness of OT as adjunctive drug therapy in PD patients would be therefore based also on the possibility to reduce the dopaminergic therapy side effects, including the impulsivity disorders mainly in patients with addictive behaviors. As a matter of fact, evidence in animal PD models is provided that OT administration may possess neuroprotective effects on dopaminergic neurons related to anti-inflammatory, antioxidant, and anti-apoptotic activities [103], that dopamine levels increased when OT was administrated [104], that the OT levels were decreased in the models, that OT supplementation rescued locomotor disabilities and anxiety-like behaviors [101], and that after intranasal administration OT concentrates in brain regions including the striatum [105]; nevertheless, studies investigating OT in PD clinical settings are still needed [106]. In fact, critical examinations appear fundamental for enabling the utilization of OT mechanisms as a curative tool in psychiatric disorders, in particular when considering that the understanding of how OT impacts social behavior is still insufficient, life experience can change the OT systems function, and the OT effects appear highly context-dependent [107].…”

Section: Potential Relevance Of Striatal Astrocytic D2-otr Heteromersmentioning

confidence: 99%

Heteromerization of Dopamine D2 and Oxytocin Receptor in Adult Striatal Astrocytes

Amato

Averna

Guidolin

et al. 2023

IJMS

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The ability of oxytocin (OT) to interact with the dopaminergic system through facilitatory D2-OT receptor (OTR) receptor-receptor interaction in the limbic system is increasingly considered to play roles in social or emotional behavior, and suggested to serve as a potential therapeutic target. Although roles of astrocytes in the modulatory effects of OT and dopamine in the central nervous system are well recognized, the possibility of D2-OTR receptor-receptor interaction in astrocytes has been neglected. In purified astrocyte processes from adult rat striatum, we assessed OTR and dopamine D2 receptor expression by confocal analysis. The effects of activation of these receptors were evaluated in the processes through a neurochemical study of glutamate release evoked by 4-aminopyridine; D2-OTR heteromerization was assessed by co-immunoprecipitation and proximity ligation assay (PLA). The structure of the possible D2-OTR heterodimer was estimated by a bioinformatic approach. We found that both D2 and OTR were expressed on the same astrocyte processes and controlled the release of glutamate, showing a facilitatory receptor-receptor interaction in the D2-OTR heteromers. Biochemical and biophysical evidence confirmed D2-OTR heterodimers on striatal astrocytes. The residues in the transmembrane domains four and five of both receptors are predicted to be mainly involved in the heteromerization. In conclusion, roles for astrocytic D2-OTR in the control of glutamatergic synapse functioning through modulation of astrocytic glutamate release should be taken into consideration when considering interactions between oxytocinergic and dopaminergic systems in striatum.

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Section: Potential Relevance Of Striatal Astrocytic D2-otr Heteromersmentioning

confidence: 99%

Heteromerization of Dopamine D2 and Oxytocin Receptor in Adult Striatal Astrocytes

Amato

Averna

Guidolin

et al. 2023

IJMS

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“…Our findings demonstrated that there was no significant difference between the TAS/TOS levels and the OSI in the serum of the Ctrl and PTZ groups. OT may have antioxidant effects in different organs; − however, we can conclude that OT may not act as an antioxidant in the serum of PTZ-kindling rats. We only calculated TAS and TOS levels and the OSI after the 3rd day of the last PTZ injections.…”

Section: Resultsmentioning

confidence: 69%

Protective Effects of Intranasally Administrated Oxytocin-Loaded Nanoparticles on Pentylenetetrazole-Kindling Epilepsy in Terms of Seizure Severity, Memory, Neurogenesis, and Neuronal Damage

ŞAHİN

Yücel

Emik

et al. 2022

ACS Chem. Neurosci.

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Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZinduced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.

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“…OXT signaling with OXTRs has been shown to inhibit activated microglia and increase the number of NKCs, a phenomenon documented in schizophrenia [221]. Recently, an OXT-generating microglial population was identified, suggesting that anti-inflammatory microglia may regulate many physiological functions that could cause pathology when disrupted [222,223].…”

Section: Oxtmentioning

confidence: 99%

The Role of Lactylation in Mental Illness: Emphasis on Microglia

et al. 2023

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A paradigm shift is currently taking place in the etiopathogenesis of neuropsychiatric disorders as immunometabolism is replacing the earlier neurotransmitter model. According to the new concept, cellular bioenergetics drives information processing in the central nervous system; therefore, neuropathology is conceptualized as a direct consequence of impaired metabolism. Along the same lines, endoplasmic reticulum stress and gut barrier dysfunction are emerging as novel targets in schizophrenia and affective disorders, linking immune responses to cellular distress. Furthermore, microglia, the brain’s innate immune cells, acquire energy through oxidative phosphorylation, while in the resting state, and glycolysis upon activation, contributing to lactate accumulation and reduced brain pH. The same metabolic signature characterizes neuropsychiatric disorders as the central nervous system derives adenosine triphosphate from aerobic glycolysis, upregulating lactate and generating an acidic environment. Although known for over three decades, the link between dysmetabolism and neuropathology was poorly defined until the discovery of brain-resident innate lymphoid cells, including natural killer cells, and lactylation of histone and nonhistone proteins. In this perspective article, we examine three anti-inflammatory microglial systems relevant for neuropsychiatry: lactate, oxytocin, and the aryl hydrocarbon receptor. We also discuss potential interventions for restoring microglial homeostasis.

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Oxytocin and Neuroprotective Effects

Cited by 4 publications

References 101 publications

Heteromerization of Dopamine D2 and Oxytocin Receptor in Adult Striatal Astrocytes

Heteromerization of Dopamine D2 and Oxytocin Receptor in Adult Striatal Astrocytes

Protective Effects of Intranasally Administrated Oxytocin-Loaded Nanoparticles on Pentylenetetrazole-Kindling Epilepsy in Terms of Seizure Severity, Memory, Neurogenesis, and Neuronal Damage

The Role of Lactylation in Mental Illness: Emphasis on Microglia

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