Oxytocin in Huntington’s disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia

Bergh, Sofia; Cheong, Rachel Y.; Petersén, Åsa; Gabery, Sanaz

doi:10.3389/fnmol.2022.984317

Cited by 3 publications

(3 citation statements)

References 101 publications

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“…It is clear that loss of OXT neurons is an early change in HD patients, primarily associated with the onset or presence of affective symptoms, and therefore, targeting the OXT system could provide a good therapeutic strategy for HD affective symptoms. Hence, based on the increasing evidence of the involvement of the OXT system in HD, 55 it would now be timely to assess the effects of OXT administration on both affective symptoms and altered social cognition in individuals with HD.…”

Section: Discussionmentioning

confidence: 99%

Effects of mutant huntingtin in oxytocin neurons on non‐motor features of Huntington's disease

Bergh

Gabery

Tonetto

et al. 2023

Neuropathology Appl Neurobio

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Background Early non‐motor features including anxiety, depression and altered social cognition are present in Huntington's disease (HD). The underlying neurobiological mechanisms are not known. Oxytocin (OXT) is involved in the regulation of emotion, social cognition and metabolism, and our previous work showed that the OXT system is affected early in HD. The aim of the study was to investigate the potential causal relationship between the selective expression of mutant huntingtin (mHTT) in OXT neurons and the development of non‐motor features and neuropathology. Methods To express mHTT only in OXT neurons, we used a novel flex‐switch adeno‐associated viral vector design to selectively express either mHTT or wild‐type HTT in the paraventricular nucleus of the hypothalamus using OXT‐Cre‐recombinase mice. We also performed a mirror experiment to selectively delete mHTT in OXT neurons using the BACHD mouse model. Mice underwent a battery of behavioural tests to assess psychiatric and social behaviours 3 months post‐injection or at 2 months of age, respectively. Post‐mortem analyses were performed to assess the effects on the OXT system. Results Our results show that selective expression of mHTT in OXT neurons was associated with the formation of mHTT inclusions and a 26% reduction of OXT‐immunopositive neurons as well as increased anxiety‐like behaviours compared with uninjected mice. However, selective deletion of mHTT from OXT neurons alone was not sufficient to alter the metabolic and psychiatric phenotype of the BACHD mice at this early time point. Conclusions Our results indicate that mHTT expression can exert cell‐autonomous toxic effects on OXT neurons without affecting the non‐motor phenotype at early time points in mice.

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Section: Discussionmentioning

confidence: 99%

Effects of mutant huntingtin in oxytocin neurons on non‐motor features of Huntington's disease

Bergh

Gabery

Tonetto

et al. 2023

Neuropathology Appl Neurobio

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“…Oxytocin (OXT) is a neuropeptide that plays an important role in the regulation of social cognition and emotional behaviors such as anxiety and depression. 46 This hormone is produced by magnocellular neurosecretory cells located in the supraoptic and PVN (which house oxytocin‐producing neurons). 47 a‐sHyp, which encompasses the PVN, exhibits notable volume loss in ALS, 22 , 23 as shown in our study.…”

Section: Discussionmentioning

confidence: 99%

Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

Ghaderi,

Fatehi,

Kalra

et al. 2024

CNS Neurosci Ther

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Background and ObjectiveAmyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non‐motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features.MethodsForty‐eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior‐superior (a‐sHyp), anterior‐inferior (a‐iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t‐tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables.ResultsThe volume of the left a‐sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = ‐0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS‐R in patients with ALS. However, right a‐sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = −0.471, p = 0.020) and left postHyp (r = −0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS‐R) scores ≤41 and >41 and those with a disease duration of 9 months or less.Discussion and ConclusionThe main finding suggests atrophy of the left a‐sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra‐motor neuroimaging finding for ALS.

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“…Patients with motor manifest and premanifest Huntington's disease have been found to have a positive correlation between OXT plasma levels and depression in a clinical study [95]. Additionally, a selective OXT loss in HD, ALS, and FTD has been linked to hypothalamic pathology [96]. OXT's anti-inflammatory and neuroprotective effects suggest that it may represent a possible therapeutic approach for the treatment of neurodegenerative and neurodevelopmental disorders.…”

Section: Neuroprotective Properties Of Oxytocinmentioning

confidence: 99%

Neuroprotective Properties of Peptides

Erbaş¹,

Altuntaş²,

Nesil³

et al. 2023

Rare Neurodegenerative Disorders - New Insights [Working Title]

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The development of a treatment strategy for neurodegenerative disorders is a serious issue for the healthcare world and a crucial subject of discussion. In the past two decades, a lot of focus has been placed on identifying the pathophysiological processes involved in neuronal death linked to neurodegenerative disorders and developing a variety of treatment options for neuroprotection. Numerous research teams have studied the use of peptides as neuroprotective treatments for different types of neurodegenerative disorders for a long time. The review aims to provide details about the roles of erythropoietin (EPO), glucagon-like peptide-1 (GLP-1), granulocyte colony-stimulating factor (G-CSF), and oxytocin (OXT) in neurodegenerative disorders as well as what cellular and molecular mechanisms they trigger to elicit the neuroprotective action, with a focus on neurodegenerative disorders.

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Oxytocin in Huntington’s disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia

Cited by 3 publications

References 101 publications

Effects of mutant huntingtin in oxytocin neurons on non‐motor features of Huntington's disease

Effects of mutant huntingtin in oxytocin neurons on non‐motor features of Huntington's disease

Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

Neuroprotective Properties of Peptides

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