A5085058969- Neuroendocrine regulation and behavior
- Hypothalamic control of reproductive hormones
- Stress Responses and Cortisol
- Circadian rhythm and melatonin
- Regulation of Appetite and Obesity
- Neuropeptides and Animal Physiology
- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Estrogen and related hormone effects
- Neuroscience of respiration and sleep
- Ovarian function and disorders
- Receptor Mechanisms and Signaling
- Plant Reproductive Biology
- Biochemical Analysis and Sensing Techniques
- Growth Hormone and Insulin-like Growth Factors
- Cholinesterase and Neurodegenerative Diseases
- Evolution and Paleontology Studies
- Neuroscience and Neuropharmacology Research
- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Electrolyte and hormonal disorders
- Nicotinic Acetylcholine Receptors Study
- Evolutionary Psychology and Human Behavior
- Phytoestrogen effects and research
- Photoreceptor and optogenetics research
King's College London
2010-2024
Bicêtre Hospital
2018
University of Gothenburg
2016
Kings Health Partners
2013-2016
Women's & Children's Health Research Institute
2001-2016
Culham Science Centre
2016
Women's Health Research Institute
2000-2015
St George's, University of London
2008
Petra Christian University
2006
University of Edinburgh
2000
Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to throughout pregnancy lactation. now report that obese (OffOb) rats display amplified prolonged neonatal leptin surge, is accompanied by elevated mRNA expression their abdominal white adipose tissue. At postnatal Day 30, before onset these animals, serum normal, but...
In rodents, a circadian signal from the suprachiasmatic nucleus (SCN) is essential for pro‐oestrous surge of gonadotrophin‐releasing hormone (GnRH), which, in turn, induces luteinising (LH) and ovulation. We hypothesised that kisspeptin (KP) neurones anteroventral periventricular preoptic nuclei (AVPV/PeN) form part communication pathway between SCN GnRH neurones. anterograde track tracing studies, we first identified vasopressin (VP)‐containing axons origin apposition to KP‐immunoreactive...
Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension adult offspring. In this study we investigated the influence of maternal rat on blood pressure regulatory pathways juvenile Obesity was induced before pregnancy female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. animals (30 days age), onset hyperleptinemia, basal nighttime mean arterial significantly raised offspring obese dams (OffOb) relative to controls...
We recently reported that soy isoflavones increase gene expression of endothelial nitric-oxide synthase (eNOS) and antioxidant defense enzymes, resulting in improved function lower blood pressure vivo. In this study, we establish equol (1-100 nM) causes acute endothelium- nitric oxide (NO)-dependent relaxation aortic rings rapidly (2 min) activates eNOS human umbilical vein cells. Intracellular Ca2+ cyclic AMP levels were unaffected by treatment (100 nM, 2 with equol, daidzein, or genistein....
Abstract Double‐label immunohistochemistry was employed to establish whether immunoreactivity for the β subtype of oestrogen receptor (ERβ‐IR) is present in gonadotropin releasing hormone (GnRH)‐containing cells. In immortalized GnRH cell line, GT1‐7, almost all nuclei were immunoreactive ERβ. preoptic area ovariectomized rats, more than one‐half neurones (52.0–63.5%) contained ERβ‐IR within nucleus; a smaller proportion these (5–10%) displayed particularly intense nuclear signal The...
Abstract In mammals, the principal circadian pacemaker is housed in hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two three VIP receptors, VPAC 2 PAC 1 , are found rat SCN. However, role remains unclear. this study, we examined phase‐resetting actions selective receptor agonists on electrical activity rhythm neurons vitro . Application during subjective day did not shift peak firing rate rhythm....
The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there great interest in identifying the adaptations responsible for these other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between mole-rats wild-derived mice. Our results indicate that genes associated with oxidoreduction mitochondria were expressed at higher relative levels mole-rats. largest effect nearly 300-fold epithelial cell adhesion molecule...
Oestrogen regulates various aspects of circadian rhythm physiology. The presence oestrogen receptors within the suprachiasmatic nucleus (SCN), principal oscillator, indicates that some actions on functions may be exerted at site. present study analysed sex differences, topographic distribution, and neurochemical phenotype neurones expressing alpha beta subtypes (ERalpha ERbeta) in mouse SCN. We found relatively few SCN are immunoreactive (IR) for ERalpha (approximately 4.5% females 3%...
Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role mediating actions E(2) gonadotrophin-releasing (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found anteroventral periventricular nucleus (AVPV) arcuate (ARC). Extensive...
The gonadotrophin-releasing hormone (GnRH) secreting neurones, which form the final common pathway for central regulation of reproduction, are directly targeted by kisspeptin (KP) via G protein-coupled receptor, GPR54. In these multiple labelling studies, we used ovariectomised mice treated with 17β-oestradiol (OVX + E(2)) or vehicle oil) to determine: (i) ultrastructural characteristics KP-immunoreactive (IR) afferents GnRH neurones; (ii) their galanin neurokinin B (NKB) content; and (iii)...
Having used the cingulate cortex to demonstrate validity of our methods for detecting hitherto unrecognized oestrogen receptor alpha (ERalpha)-immunoreactive neurones, we have now employed immunoprecipitation and double-label immunohistochemistry investigate whether ERalpha protein is present in gonadotrophin-releasing hormone (GnRH)-containing cells. The immortalized GnRH cell line GT1-7 neurones within rat preoptic area were found possess ERalpha-immunoreactivity (ERalpha-IR). These...
The substantia nigra pars reticulata (SNr) plays a key role in basal ganglia function. Projections from multiple nuclei converge at the SNr to regulate nigrothalamic output. is also characterized by abundant aminergic input, including dopaminergic dendrites and axons containing 5-hydroxytryptamine (5-HT) or histamine (HA). functions of HA include motor control via H 3 receptors (H Rs), although mechanism remains far elucidated. In Parkinson's disease, there an increase Rs density...
Abstract Topographical distribution of estrogen receptor‐β (ER‐β)‐synthesizing oxytocin (OT) and vasopressin (VP) neurons was studied in the hypothalamic paraventricular supraoptic nuclei (PVH; SO) ovariectomized rats. In distinct subregions, 45–98% OT 88–99% VP exhibited ER‐β immunoreactivity that confined to cell nuclei. Neuronal populations differed markedly with respect intensity signal. Magnocellular PVH, SO, accessory groups typically contained low levels signal; contrast, robust...
The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a superfamily of structurally related hormones that includes glucagon, glucagon-like peptides, secretin, growth hormone-releasing hormone. Microinjection VIP or PACAP into the rodent suprachiasmatic nucleus (SCN) phase shifts circadian pacemaker antagonists, antisense oligodeoxynucleotides have been shown disrupt function. equal potency as agonists VPAC 2 receptor...
The roles of the adrenergic projection to paraventricular nucleus (PVN) and central CRH in suppression pulsatile LH secretion during 48-h fasting were examined ovariectomized estradiol (E2)-treated rats. animals immediately implanted with Silastic tubing containing E2. One week after ovariectomy E2 implantation, stereotaxically a guide cannula for microinjection into PVN or intracerebroventricular (icv) injection. later, some deprived food 48 h. unfasted controls provided ad libitum. At this...
African mole-rats provide a unique taxonomic group for investigating the evolution and neurobiology of sociality. The two species investigated here display extreme differences in social organization reproductive strategy. Naked (NMRs) live colonies, dominated by queen her consorts; most members remain nonreproductive throughout life but cooperate burrowing, foraging, caring pups, which they are not biological parents (alloparenting). In contrast, Cape (CMRs) solitary intolerant conspecifics,...
Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action orexin the regulation LH have been investigated vivo ovariectomized rats that were given vehicle or estradiol benzoate (EB), with without an injection progesterone 48 h later. was administered intrahypothalamically under Saffan anesthesia, 50 after EB vehicle; its effects on plasma levels monitored sequential blood samples. (1.0 μg/side) injected into rostral preoptic area (rPOA) at level organum...
The prevalence of obesity among pregnant women is increasing. Evidence from human cohort studies and experimental animals suggests that offspring cardiovascular metabolic function compromised through early life exposure to maternal obesity. Previously, we reported juvenile obese rats develop sympathetically mediated hypertension associated with neonatal hyperleptinemia. We have now addressed the hypothesis raised leptin in immediate postnatal period plays a causal role. Pups lean...
Abstract Introduction The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood. Methods Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts—AD a transgenic mouse model—to investigate T14, 14mer peptide, as key signaling molecule the neuropathology. Results T14 increases AD brains progresses conspicuous 5XFAD mice, where its immunoreactivity corresponds to that seen AD: neurons immunoreactive for...
Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans. The aims of this study were 2-fold: 1) to determine vivo whether genistein coumestrol act the GnRH pulse generator suppress hypothalamic multiunit electrical activity volleys associated LH pulses and/or pituitary response GnRH; 2) examine effect these phytoestrogens GnRH-induced release vitro estrogen receptors are involved. Wistar rats ovariectomized chronically implanted with recording...
Abstract Corticotropin‐releasing hormone (CRH) is implicated in the suppression of pulsatile luteinizing (LH) secretion by a variety stressful stimuli; 17β‐oestradiol (E 2 ) has been shown to modulate this inhibitory response. The present study ovariectomized (OVX) rats was designed investigate effect E and progesterone (P 4 on hypoglycaemic stress‐induced changes LH associated both central peripheral components hypothalamic‐pituitary‐adrenal axis. enhanced pulses; P addition further...
Abstract The suprachiasmatic nucleus (SCN) contains the predominant circadian pacemaker in mammals. Considerable evidence indicates that VPAC 2 and PAC 1 , receptors for vasoactive intestinal peptide (VIP) pituitary adenylate cyclase‐activating (PACAP), play critical roles maintaining entraining rhythms. Retinal projections to rat SCN contain PACAP terminate mostly ventral SCN, site of VIP neurons. incidence mRNAs within distinct neuronal populations has been determined using double‐label...