Oxytocin receptor is a potential biomarker of the hyporesponsive HPA axis subtype of PTSD and might be modulated by HPA axis reactivity traits in humans and mice

Hofmann, Julia; Huber, Christian G.; Novak, Božidar; Schreckenbach, Monika; Schubert, Christine F.; Touma, Chadi; Rutten, Bart P. F.; Schmidt, Ulrike

doi:10.1016/j.psyneuen.2021.105242

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…To test this hypothesis, we first collected hippocampal samples in P14 mice with or without whisker trimming experience at P12. Then, using an ELISA assay [ 43 ], we found that the 2-day previous whisker trimming had significantly reduced the hippocampal OXT, but not the vasopressin levels (Fig. 5a ).…”

Section: Resultsmentioning

confidence: 99%

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice

Pan

Zheng

et al. 2022

Mol Psychiatry

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Early sensory experiences interact with genes to shape precise neural circuits during development. This process is vital for proper brain function in adulthood. Neurological dysfunctions caused by environmental alterations and/or genetic mutation may share the same molecular or cellular mechanisms. Here, we show that early life bilateral whisker trimming (BWT) subsequently affects social discrimination in adult male mice. Enhanced activation of the hippocampal dorsal CA3 (dCA3) in BWT mice was observed during social preference tests. Optogenetic activation of dCA3 in naive mice impaired social discrimination, whereas chemogenetic silencing of dCA3 rescued social discrimination deficit in BWT mice. Hippocampal oxytocin (OXT) is reduced after whisker trimming. Neonatal intraventricular compensation of OXT relieved dCA3 over-activation and prevented social dysfunction. Neonatal knockdown of OXT receptor in dCA3 mimics the effects of BWT, and cannot be rescued by OXT treatment. Social behavior deficits in a fragile X syndrome mouse model (Fmr1 KO mice) could also be recovered by early life OXT treatment, through negating dCA3 over-activation. Here, a possible avenue to prevent social dysfunction is uncovered.

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Section: Resultsmentioning

confidence: 99%

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice

Pan

Zheng

et al. 2022

Mol Psychiatry

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“…Atosiban(ATO; HY-17572A; MedChemExpress;) was diluted in saline and administered intraperitoneally (1.5 mg/kg/d for i.p. [ 43 ], 50 ng for hippocampal stereotactic injection [ 41 ]) Clozapine N-oxide (CNO) (K948133-100 mg; ShangHai D&B Biological Science and Technology Co. Ltd) was diluted in 5% DMSO and administered intraperitoneally (3 mg/kg/d).…”

Section: Methodsmentioning

confidence: 99%

Oxytocin attenuates hypothalamic injury-induced cognitive dysfunction by inhibiting hippocampal ERK signaling and Aβ deposition

Wu,

Ou,

Feng

et al. 2024

Transl Psychiatry

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In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic–pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.

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“…During TSST, an increase in OXTR mRNA was markedly correlated with PTSD symptoms. It should be noted, however, that these findings apply only to the HPA axis hyporesponsive subtype of PTSD in the study [ 203 ]. However, due to the small sample size and opposing findings in other studies [ 212 ], it is still early to consider oxytocin a reliable biomarker for PTSD.…”

Section: Ptsd Biomarkersmentioning

confidence: 99%

To Predict, Prevent, and Manage Post-Traumatic Stress Disorder (PTSD): A Review of Pathophysiology, Treatment, and Biomarkers

Jowf

Ahmed

Reijnders

et al. 2023

IJMS

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Post-traumatic stress disorder (PTSD) can become a chronic and severely disabling condition resulting in a reduced quality of life and increased economic burden. The disorder is directly related to exposure to a traumatic event, e.g., a real or threatened injury, death, or sexual assault. Extensive research has been done on the neurobiological alterations underlying the disorder and its related phenotypes, revealing brain circuit disruption, neurotransmitter dysregulation, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Psychotherapy remains the first-line treatment option for PTSD given its good efficacy, although pharmacotherapy can also be used as a stand-alone or in combination with psychotherapy. In order to reduce the prevalence and burden of the disorder, multilevel models of prevention have been developed to detect the disorder as early as possible and to reduce morbidity in those with established diseases. Despite the clinical grounds of diagnosis, attention is increasing to the discovery of reliable biomarkers that can predict susceptibility, aid diagnosis, or monitor treatment. Several potential biomarkers have been linked with pathophysiological changes related to PTSD, encouraging further research to identify actionable targets. This review highlights the current literature regarding the pathophysiology, disease development models, treatment modalities, and preventive models from a public health perspective, and discusses the current state of biomarker research.

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Oxytocin receptor is a potential biomarker of the hyporesponsive HPA axis subtype of PTSD and might be modulated by HPA axis reactivity traits in humans and mice

Cited by 9 publications

References 43 publications

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice

Oxytocin attenuates hypothalamic injury-induced cognitive dysfunction by inhibiting hippocampal ERK signaling and Aβ deposition

To Predict, Prevent, and Manage Post-Traumatic Stress Disorder (PTSD): A Review of Pathophysiology, Treatment, and Biomarkers

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