NPY1 Receptor Agonist Modulates Development of Depressive-Like Behavior and Gene Expression in Hypothalamus in SPS Rodent PTSD Model

Serova, Lidia; Mulhall, Hannah; Sabban, Esther L.

doi:10.3389/fnins.2017.00203

Cited by 27 publications

(22 citation statements)

References 41 publications

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“…Additionally, it prevented activation of the HPA axis and the locus coeruleus-noradrenergic system [ 12 ]. Similar results were obtained when NPY was administered immediately after exposure to stress (early intervention) [ 12 , 55 , 56 , 153 , 154 ]. Intranasal NPY effectively reversed hyperarousal, depressive-like and anxiety behavior seen in vehicle-treated animals when it was given a week or more after exposure to stress [ 137 , 155 ].…”

Section: Sex Differences In Response To Npy Administrationsupporting

confidence: 77%

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders

Nahvi

Sabban

2020

Biomolecules

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The neuropeptide Y (NPY) system is emerging as a promising therapeutic target for neuropsychiatric disorders by intranasal delivery to the brain. However, the vast majority of underlying research has been performed with males despite females being twice as susceptible to many stress-triggered disorders such as posttraumatic stress disorder, depression, anorexia nervosa, and anxiety disorders. Here, we review sex differences in the NPY system in basal and stressed conditions and how it relates to varied susceptibility to stress-related disorders. The majority of studies demonstrate that NPY expression in many brain areas under basal, unstressed conditions is lower in females than in males. This could put them at a disadvantage in dealing with stress. Knock out animals and Flinders genetic models show that NPY is important for attenuating depression in both sexes, while its effects on anxiety appear more pronounced in males. In females, NPY expression after exposure to stress may depend on age, timing, and nature and duration of the stressors and may be especially pronounced in the catecholaminergic systems. Furthermore, alterations in NPY receptor expression and affinity may contribute to the sex differences in the NPY system. Overall, the review highlights the important role of NPY and sex differences in manifestation of neuropsychiatric disorders.

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Section: Sex Differences In Response To Npy Administrationsupporting

confidence: 77%

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders

Nahvi

Sabban

2020

Biomolecules

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“…To investigate depression‐like behaviours, we employed the conventional sucrose preference test in the Scn1a +/− mice (Serova et al, ). This task is based on the assumption that depression‐like behaviour in rodents inversely correlates with sucrose preference (Murray et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The sucrose preference test was carried out to assess the depression‐like behaviour (Serova, Mulhall, & Sabban, ). The animals were separately housed during this test.…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

Patra

Serafeimidou‐Pouliou

Bazelot

et al. 2020

British J Pharmacology

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Background and Purpose: Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and co-morbidities such as anxiety, depression, autism, motor dysfunction and memory deficits. Cannabidiol is an approved anticonvulsive drug in the United States and Europe for seizures associated with Dravet syndrome in patients 2 years of age and older. We investigated its potential to prevent premature mortality and improve associated co-morbidities. Experimental Approach:The efficacy of sub-chronic cannabidiol administration in two mouse models of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a −/− mice. We then used a hybrid, heterozygote Scn1a +/− mouse model to study the effect of cannabidiol on survival and behavioural co-morbidities: motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). Key Results:In Scn1a −/− mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a +/− mice, chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. Conclusion and Implications:We are the first to demonstrate a potential diseasemodifying effect of cannabidiol in animal models of Dravet syndrome. Cannabidiol treatment reduced premature mortality and improved several behavioural comorbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural co-morbidities associated with Dravet syndrome.

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“…Animals were exposed to the SPS protocol between 9 am and 2 pm as previously described . They were immobilized for 2 h on a metal board by taping the limbs with surgical tape and restricting the motion of the head and then immediately subjected to a forced swim for 20 min in plexiglass cylinder (50 cm height, 24 cm diameter, Stoelting, Wood Dale, IL) filled two‐thirds with 24 °C fresh water.…”

Section: Methodsmentioning

confidence: 99%

Preclinical findings on the potential of intranasal neuropeptide Y for treating hyperarousal features of PTSD

Nwokafor

Serova

Sabban

2019

Annals of the New York Academy of Sciences

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Acoustic startle response (ASR) assesses hyperarousal, a core symptom of posttraumatic stress disorder (PTSD). Intranasal neuropeptide Y (NPY) administration was shown to prevent hyperarousal in single prolonged stress (SPS) rodent PTSD model. However, it is unclear how ASR itself alters responses to stress. Rats (A-S-A) were exposed to acoustic startle (AS) 1 day before SPS (ASR1) and 2 weeks afterward (ASR2). Other groups were exposed in parallel to either AS (A-A) or SPS or neither. SPS enhanced ASR2. In relevant brain areas, mRNA levels were determined by qRT-PCR. In mediobasal hypothalamus, AS or SPS each increased CRH mRNA levels without an additive effect. Exposure to AS appeared to dampen some responses to SPS. The SPS-triggered reduction of GR and FKBP5 gene expression was not observed in A-S-A group. In locus coeruleus, SPS increased CRHR1 and reduced Y2R mRNAs, but not in A-S-A group. In both regions, AS altered NPY receptor gene expression, which may mediate dampening responses to SPS. In second experiment, intranasal NPY administered 2 weeks after SPS reversed hyperarousal symptoms for at least 7 days. This study reveals important effects of AS on the NPY system and demonstrates that intranasal NPY elicits long-lasting reversal of traumatic stress-triggered hyperarousal.

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NPY1 Receptor Agonist Modulates Development of Depressive-Like Behavior and Gene Expression in Hypothalamus in SPS Rodent PTSD Model

Cited by 27 publications

References 41 publications

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders

Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

Preclinical findings on the potential of intranasal neuropeptide Y for treating hyperarousal features of PTSD

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