Sex-Specific Regulation of Behavioral Responses to Single Prolonged Stress: Role of PACAP DOI Creative Commons
Marissa A. Smail, Evelin M. Cotella,

Susan E. Martelle

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

ABSTRACT Post-Traumatic Stress Disorder (PTSD) is a debilitating condition in which traumatic experience triggers symptoms related to re-experiencing, avoidance, arousal, and mood dysregulation. PTSD negatively impacts 6% of people during their lifetime, with women being disproportionally affected exhibiting different, more severe than men. Despite this widespread impact, the molecular mechanisms underlying its sex differences remain poorly understood. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) neuropeptide participates fine-tuning circuitry throughout brain has been associated humans, especially women. Here, we use Single Prolonged (SPS), an animal model PTSD, explore roles PACAP PTSD-like behaviors. Specifically, agonist or antagonist was infused into infralimbic (IL) prefrontal cortex, region key regulating fear- anxiety-related behaviors, prior SPS male female rats. One week later, rats were tested open field/novel object, elevated plus maze, social interaction. Utilizing behavioral indexing method, able uncover effects PTSD-related domains that differentially impacted by manipulations males females. While both sexes exhibited increased threat avoidance decreased assessment following SPS, females sociability while sociability. Males also appeared be protected IL antagonism phenotypes exacerbated agonism. Furthermore, RNAscope revealed cortex responds differently Together, these findings suggest complex relationships between sex, may have important implications for treating men HIGHLIGHTS induces different increases decreases appraisal Sociability but manipulation exerts diverging Prefrontal signaling plays sex-specific role

Language: Английский

Role of PACAP in migraine: An alternative to CGRP? DOI Creative Commons
Song Guo, Inger Jansen‐Olesen, Jes Olesen

et al.

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 176, P. 105946 - 105946

Published: Dec. 5, 2022

Migraine is a widespread and debilitating neurological condition affecting more than billion people worldwide. Thus, effective migraine therapies are highly needed. In the last decade, two endogenous neuropeptides, calcitonin gene-related peptide (CGRP) pituitary adenylate cyclase-activating (PACAP), were identified to be implicated in migraine. Recently, introduction of monoclonal antibodies (mAbs) blocking CGRP most important advance therapy for decades. However, 40% patients unresponsive these new drugs. We believe that PACAP may involved patients. Like CGRP, located sensory nerve fibers, it dilates cranial arteries, causes when infused into lends itself antibody therapy. Also, recent studies suggest pathway independent pathway. Understanding signaling pathways therefore lead identification novel therapeutic targets particular interest anti-CGRP Accordingly, neutralizing mAb currently clinical phase II development. The aim present review is, therefore, give thorough account existing data on PACAP, its receptors relation

Language: Английский

Citations

33
Human pluripotent stem cell-derived ectomesenchymal stromal cells promote more robust functional recovery than umbilical cord-derived mesenchymal stromal cells after hypoxic-ischaemic brain damage DOI Creative Commons
Jiawei Huang,

Kin Pong U,

Fuyuan Yang

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 12(1), P. 143 - 166

Published: Nov. 10, 2021

Aims: Hypoxic-ischaemic encephalopathy (HIE) is one of the most serious complications in neonates and infants.Mesenchymal stromal cell (MSC)-based therapy emerging as a promising treatment avenue for HIE.However, despite its enormous potential, clinical application MSCs limited by heterogeneity, low isolation efficiency unpredictable effectiveness.In this study, we examined therapeutic effects underlying mechanisms human pluripotent stem cell-derived ectomesenchymal cells (hPSC-EMSCs) rat model HIE.Methods: hPSC-EMSCs were induced from either embryonic or cells.Stem conditioned medium (CM) derived delivered intracranially intranasally to neonatal rats with HIE.Human umbilical cord-derived (hUC-MSCs) used comparison control phosphate-buffered saline (PBS) was negative control.Lesion size, apoptosis, neurogenesis, astrogliosis microgliosis evaluated.The rotarod test Morris water maze determine brain functional recovery.The PC-12 line, primary cortical neurons neural progenitor evaluate neurite outgrowth neuroprotective neurogenesis hPSC-EMSCs/hUC-MSCs.RNA-seq enzyme-linked immunosorbent assays secretory factors that differentially expressed between hUC-MSCs.The activation suppression extracellular signal-regulated kinase (ERK) cAMP response element-binding protein (CREB) characterised using western blotting immunofluorescent staining.Results: showed higher potential than hUC-MSCs, demonstrated more significant reduction lesion size apoptosis following hypoxia-ischaemia (HI).Compared PBS treatment, promoted endogenous alleviated microgliosis.hPSC-EMSCs effective hUC-MSCs.hPSC-EMSCs achieved greater recovery function hUC-MSCs HIE.CM had neurorestorative vitro through anti-apoptotic outgrowth-and neurogenesis-promoting effects.Direct comparisons revealed enrichment group hPSC-EMSCs, including nerve growth factor (NGF), platelet-derived factor-AA transforming factor-β2, which are involved synaptic transmission neurotransmitter transport, respectively.Mechanistically, CM found potentiate NGF-induced neuronal differentiation Ivyspring International PublisherNPCs via ERK/CREB pathway.Suppression ERK CREB abolished CM-potentiated neuritogenesis differentiation.Finally, intranasal delivery significantly reduced mitigated inflammatory responses improved HIE.Conclusion: promote after HI multifaceted neuromodulatory activities paracrine/trophic mechanisms.We propose use HIE, they offer an excellent unlimited cellular source MSCs.

Language: Английский

Citations

33
Young adult and aged female rats are vulnerable to amygdala-dependent, but not hippocampus-dependent, memory impairment following short-term high-fat diet DOI Creative Commons
Stephanie Muscat, Michael J. Butler, Sabrina Mackey-Alfonso

et al.

Brain Research Bulletin, Journal Year: 2023, Volume and Issue: 195, P. 145 - 156

Published: March 2, 2023

Global populations are increasingly consuming diets high in saturated fats and refined carbohydrates, such have been well-associated with heightened inflammation neurological dysfunction. Notably, older individuals particularly vulnerable to the impact of unhealthy diet on cognition, even after a single meal, pre-clinical rodent studies demonstrated that short-term consumption high-fat (HFD) induces marked increases neuroinflammation cognitive impairment. Unfortunately though, date, most topic nutrition especially aging, performed only male rodents. This is concerning given females more develop certain memory deficits and/or severe memory-related pathologies than males. Thus, aim present study was determine extent which HFD impacts function female rats. Young adult (3 months) aged (20–22 rats were fed for 3 days. Using contextual fear conditioning, we found had no effect long-term (hippocampus-dependent) at either age, but impaired auditory-cued (amygdala-dependent) regardless age. Gene expression Il-1β markedly dysregulated amygdala, not hippocampus, both young days HFD. Interestingly, modulation IL-1 signaling via central administration receptor antagonist (which previously be protective males) following females. Investigation memory-associated gene Pacap its Pac1r revealed differential effects their hippocampus amygdala. Specifically, induced increased whereas decreased observed Collectively, these data suggest amygdala-dependent (but hippocampus-dependent) impairments consumption, identify potential mechanisms related IL-1β PACAP effects. findings strikingly different those reported using same regimen behavioral paradigms, highlight importance examining sex differences context neuroimmune-associated

Language: Английский

Citations

10
Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective DOI Creative Commons

Catherine E. Van Doorn,

Mikala Zelows,

Anel A. Jaramillo

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 5, 2025

The neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) plays a pivotal role in regulating stress, fear, and anxiety responses. Genetic molecular studies investigating PACAP demonstrate sex-dimorphic characteristics, with females exhibiting increased reactivity of signaling neuropsychiatric disorders. Studies expand the to substance use disorders (SUD) by demonstrating modulation can lead neurobiological changes induced nicotine, ethanol, stimulants opioids. Given that SUD exhibit distinct drug use, relapse, withdrawal sensitivity relative males, we hypothesize system contributes these sex-specific differences. Therefore, review characterizing at molecular, brain regional, behavioral levels relevant addiction cycle. We present literature linking disorders, which intricate within neuronal pathways modulating addiction. are more particularly susceptible PACAP-related during intoxication phases Altogether understanding differences offers foundation for future aimed developing tailored interventions addressing SUD.

Language: Английский

Citations

0
Regulation of Behavioral Responses to Single Prolonged Stress in Male and Female Rats: Role of PACAP DOI Creative Commons
Marissa A. Smail, Evelin M. Cotella,

Susan E. Martelle

et al.

Neurobiology of Stress, Journal Year: 2025, Volume and Issue: unknown, P. 100727 - 100727

Published: April 1, 2025

Language: Английский

Citations

0
Post-operative cognitive dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary DHA supplementation DOI
Stephanie Muscat, Michael J. Butler,

Menaz N. Bettes

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 116, P. 385 - 401

Published: Dec. 23, 2023

Language: Английский

Citations

7
Chronic treatment of mixture of two iridoids proportional to prescriptional dose of Yueju improves hippocampal PACAP-related neuroinflammation and neuroplasticity signaling in the LPS-induced depression model DOI

Zhangjie Wu,

Ying Yin, Ruiyi Liu

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 338, P. 119031 - 119031

Published: Nov. 8, 2024

Language: Английский

Citations

2
Shorebirds’ Longer Migratory Distances Are Associated With Larger ADCYAP1 Microsatellites and Greater Morphological Complexity of Hippocampal Astrocytes DOI Creative Commons
Diego de Almeida Miranda, Juliana Araripe, Nara Gyzely de Morais Magalhães

et al.

Frontiers in Psychology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 4, 2022

For the epic journey of autumn migration, long-distance migratory birds use innate and learned information follow strict schedules imposed by genetic epigenetic mechanisms, details which remain largely unknown. In addition, bird migration requires integrated action different multisensory systems for learning memory, hippocampus appears to be integration center this task. previous studies we found that contrasting flights differentially affected morphological complexity two types astrocytes. Recently, a significant association was between latitude reproductive site size ADCYAP1 allele in long distance birds. We tested correlations astrocyte complexity, distances, three migrant species shorebird one non-migrant. Significant differences among were number astrocytes, as well microsatellites gene. associations microsatellites, degree suggest microsatellite size, behavior may part adaptive response process shorebirds.

Language: Английский

Citations

10
Demystifying the Neuroprotective Role of Neuropeptides in Parkinson’s Disease: A Newfangled and Eloquent Therapeutic Perspective DOI Open Access
Tapan Behl, Piyush Madaan, Aayush Sehgal

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4565 - 4565

Published: April 20, 2022

Parkinson's disease (PD) refers to one of the eminently grievous, preponderant, tortuous nerve-cell-devastating ailments that markedly impacts dopaminergic (DArgic) nerve cells midbrain region, namely substantia nigra pars compacta (SN-PC). Even though exact etiopathology ailment is yet indefinite, existing corroborations have suggested aging, genetic predisposition, and environmental toxins tremendously influence PD advancement. Additionally, pathophysiological mechanisms entailed in advancement encompass clumping α-synuclein inside lewy bodies (LBs) neurites, oxidative stress, apoptosis, neuronal-inflammation, abnormalities operation mitochondria, autophagy lysosomal pathway (ALP), ubiquitin-proteasome system (UPS). The ongoing therapeutic approaches can merely mitigate PD-associated manifestations, but until now, no candidate has been depicted fully arrest Neuropeptides (NPs) are little, protein-comprehending additional messenger substances typically produced liberated by within entire nervous system. Numerous NPs, for instance, substance P (SP), ghrelin, neuropeptide Y (NPY), neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), nesfatin-1, somatostatin, displayed exhibit consequential neuroprotection both vivo vitro models via suppressing cytotoxicity, inflammation, autophagy, neuronal toxicity, microglia stimulation, attenuating disease-associated stimulating chondriosomal bioenergetics. current scrutiny an effort illuminate neuroprotective action NPs various PD-experiencing models. authors carried out a methodical inspection published work procured through reputable online portals like PubMed, MEDLINE, EMBASE, Frontier, employing specific keywords subject our article. manuscript concentrates on representing pathways concerned bringing PD. In sum, exert substantial regulating paramount indulged advancement, consequently, might be newfangled eloquent perspective therapy.

Language: Английский

Citations

10
Increased pituitary adenylate cyclase-activating peptide genes expression in the prefrontal cortex in schizophrenia in relation to suicide DOI Creative Commons

Zala Slabe,

Rawien Balesar,

R.W.H. Verwer

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Nov. 2, 2023

Pituitary adenylate cyclase-activating peptide (PACAP) is a stress-related neuropeptide that produced in several brain areas. It acts by 3 receptors: PACAP type-1 (PAC1), vasoactive intestinal (VIP) -1 and -2 (VPAC1 2). Data on polymorphisms PAC1 indicate relationship of the system with schizophrenia (SCZ).The prefrontal cortex was chosen to measure PACAP-gene related expression changes, since this central structure symptoms (SCZ). We investigated alterations PACAP-related genes qPCR human dorsolateral (DLPFC) anterior cingulate (ACC) 35 SCZ patients 34 matched controls relation SCZ, suicide, gender medication.The ACC revealed an upregulation PACAP, PAC1, VPAC1 VPAC2 suicide (S) completers compared controls. An increase also present SCZ-S who died naturally (SCZ-N). In DLPFC, found SCZ-N Moreover, all male females. Concluding, changes were gender. particular, there higher gene DLPFC SCZ.These findings suggest potential link between pathophysiology suicide. Further research needed understand functional significance clinical applications these changes.

Language: Английский

Citations

4