Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY

Serova, Lidia; Nwokafor, Chiso; Bockstaele, Elisabeth J. Van; Reyes, Beverly A.S.; Lin, Xiaoping; Sabban, Esther L.

doi:10.1016/j.euroneuro.2019.02.010

Cited by 35 publications

(40 citation statements)

References 47 publications

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“…We previously showed that CRHR1 mRNA levels are increased in animals 1 week after exposure to SPS . In this study, we found the elevation of CRHR1 mRNA levels 2 weeks after exposure to SPS, which is consistent with our previous study . However, to our surprise, in the A‐S‐A group that had ASR1 measurement before exposure to SPS and ASR2 measurements 2 weeks after SPS, CRHR1 mRNA levels were similar to the unstressed control and to the A‐A group.…”

Section: Discussionsupporting

confidence: 92%

“…Abnormal startle response and many SPS‐triggered impairments could be attenuated by either prophylactic or early intervention with intranasal NPY . It was also able to reverse elevation in anxiety, depressive‐like behavior, and acoustic startle response (ASR) when given 1 or 2 weeks after SPS stressors . These findings support the delivery of NPY specifically to the brain regions by intranasal infusion as an efficient way to prevent and treat the development of PTSD …”

Section: Introductionmentioning

confidence: 66%

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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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 66%

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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“…Male-specific changes within the Y2R system are also seen after exposure to stress. We observed a decrease in Y2R gene expression levels in the locus coeruleus after single prolonged stress as compared to unstressed controls only in males [ 56 , 136 , 137 ]. A decrease in Y2R expression would allow for more NPY and other neurotransmitters to be released into the synapse.…”

Section: Sex Differences In Brain-related Npy Receptor Expression mentioning

confidence: 92%

“…This hyper-reactive locus coeruleus includes increased afferents receiving input from the limbic system and CRHR1 availability in females [ 114 , 116 ]. Furthermore, this elevation of Y1R gene expression levels was not seen in males, suggesting the potential importance of Y1R in females [ 56 , 137 ].…”

Section: Sex Differences In Brain-related Npy Receptor Expression mentioning

confidence: 99%

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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“…In the hippocampus, a hypothalamus-specific gene expression was modified by them. Chronic stress-induced elevations in corticosterone, proinflammatory cytokine levels, depression-like, and anxiety-like behavior can be reduced by FOS + GOS (Burokas et al 2017;Serova et al 2019). In infants also, prebiotics plays an essential role in maintaining the health of the baby.…”

Section: Applications Of Prebioticsmentioning

confidence: 99%

Prospecting prebiotics, innovative evaluation methods, and their health applications: a review

Khangwal

Shukla

2019

3 Biotech

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Prebiotics are necessary natural and synthetic food ingredients that help in the growth and development of gut microflora. There is a complex relationship between gut dysbiosis and microbes, so alteration in both probiotics and prebiotics can reduce illness of gut, which further plays a decisive role in human health. The prebiotic efficiency can be validated using various in vitro and in vivo experiments, and this gives an important insight to this field. This review focuses on these aspects including the standardized assessment of prebiotics and its metabolic products for customary applications. This review has also summarized the mechanism of their beneficial actions such as immunomodulation, nutrient absorption, pathogen inhibition, etc., and its significance in human nutrition. In addition to this, some fascinating applications of prebiotics in health-related disorders have also discussed, with current challenges in this facet.

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Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY

Cited by 35 publications

References 47 publications

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

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

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

Prospecting prebiotics, innovative evaluation methods, and their health applications: a review

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