A5060097781- Estrogen and related hormone effects
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Retinoids in leukemia and cellular processes
- Biotin and Related Studies
- Neuroendocrine regulation and behavior
- Menopause: Health Impacts and Treatments
- Alzheimer's disease research and treatments
- Hypothalamic control of reproductive hormones
- Retinal Development and Disorders
- Phosphodiesterase function and regulation
- Air Quality Monitoring and Forecasting
- Nuclear Structure and Function
- Functional Brain Connectivity Studies
- Memory and Neural Mechanisms
- Zebrafish Biomedical Research Applications
- Ocular and Laser Science Research
- Membrane-based Ion Separation Techniques
- Membrane Separation Technologies
- Cellular transport and secretion
- Cell Image Analysis Techniques
- Cholinesterase and Neurodegenerative Diseases
King's College London
2012-2023
Neuroscience Institute
2016-2023
Kensington College of Business
2017
Abstract Introduction Synapse loss is the structural correlate of cognitive decline indicative dementia. In brains Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble are toxic synapses. We previously demonstrated that Aβ induces Dickkopf‐1 (Dkk1), which in turn activates Wnt–planar cell polarity (Wnt‐PCP) pathway drive tau pathology and neuronal death. Methods compared effects Dkk1 on synapse morphology memory impairment while inhibiting or...
Variation in the gene encoding zinc finger binding protein 804A (ZNF804A) is associated with schizophrenia and bipolar disorder. Evidence suggests that ZNF804A a regulator of transcription present nuclear extranuclear compartments. However, detailed examination distribution its neuronal functions has yet to be performed.The localization was examined neurons derived from human neural progenitor cells, induced pluripotent stem or primary rat cortical neurons. In addition, small interfering...
In the mammalian forebrain, majority of excitatory synapses occur on dendritic spines. Changes in number these structures is important for brain development, plasticity and refinement neuronal circuits. The formation involves coordinated spines targeting multi-protein complexes to nascent connections. Recent studies have demonstrated that estrogen 17β-estradiol (E2) can rapidly increase spines, an effect consistent with ability E2 influence cognitive function. However, molecular composition...
The thalamus is often defined as the 'gateway to consciousness', a feature that supported by specific connectivity and electrophysiological properties of its neurons. Inhibitory GABAergic neurons are required for dynamic gating information passing through thalamus. high degree heterogeneity among thalamic GABA suggests that, during embryonic development, alternative differentiation programmes exist guide acquisition inhibitory neuron subtype identity. Taking advantage accessibility...
Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain influence development, female reproduction, anxiety, stress. Hormone-activated PRs associate with multiple proteins form functional complexes. In present study, from mouse hypothalamus that PR were isolated using affinity pull-down assays glutathione S-transferase-tagged PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) mass spectrometry, we identified hypothalamic interact a...
Abstract Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic studies SCZ MDD using in vivo vitro systems have supported role for dysfunction excitatory the pathophysiology these disorders. Recent clinical demonstrated that estrogen, 17β-estradiol can ameliorate many symptoms experienced by patients. Yet, date, our understanding how exerted beneficial...
Oestrogens play an important role in brain development where they have been implicated controlling various cellular processes. Several lines of evidence presented showing that oestrogens can be synthesized locally within the brain. Studies demonstrated aromatase, enzyme responsible for conversion androgens to oestrogens, is expressed during early both male and female cortices. Furthermore, 17β-oestradiol has measured foetal tissue from multiple species. regulates neural progenitor...
Abstract The cell-adhesion proteins neuroligin-3 and neuroligin-4X (NLGN3/4X) have well described roles in synapse formation. NLGN3/4X are also expressed highly during neurodevelopment. However, the role these play this period is unknown. Here we show that localized to leading edge of growth cones where it promoted neuritogenesis immature human neurons. Super-resolution microscopy revealed clustering induced cone enlargement influenced actin filament organization. Critically, morphological...
Estrogens have been shown to rapidly regulate local signalling at synapses and within the nucleus. The result of these events is modulate synapse structure function, as well epigenetic mechanisms including histone modifications. Ultimately are thought contribute long-lasting changes in neural circuitry, thus influence cognitive functions such learning memory. However, by which estrogen-mediated synaptic nuclear coordinated not understood. In this study we found that scaffold protein afadin,...
Abstract Estrogens, specifically 17β-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of proteins. However, mechanisms underlying estradiol’s regulation protein expression, whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures mixed-sex primary neurons, we investigated local synthesis required for estradiol- induced expression. Estradiol rapidly increased rate...
Increased levels of Aβ destroy the connections between nerve cells. This synaptotoxic property is likely main driver Alzheimer's disease. Our contention that this key effect driven by dysregulation Wnt signaling, primarily Wnt-PCP-RhoA/ROCK pathway. Primary rodent cortical neuronal cultures, adult rats and transgenic mice were treated with or canonical antagonist Dickkopf-1 (Dkk1), plus minus ROCK inhibitors an siRNA directed against a element Wnt-PCP Dendritic spine morphology in...
Abstract Estrogens have been shown to rapidly regulate local signalling events at both synapses and within the nucleus. The result of these is modulate synapse structure function, as well epigenetic mechanisms including histone modifications. Ultimately are thought contribute long-lasting changes in neural circuitry, thus influences cognitive functions such learning memory. However, by which estrogen-mediated synaptic nuclear coordinated not understood. In this study we found that scaffold...
Abstract Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic studies SCZ MDD using in vivo vitro systems have supported role for dysfunction excitatory the pathophysiology these disorders. Recent clinical demonstrated that estrogen, 17β-estradiol can ameliorate many symptoms experienced by patients. Yet, date, our understanding how exerted beneficial...
Abstract Estrogens play an important role in the sexual dimorphisms that occur during brain development, including neural circuitry underlies sex-typical and socio-aggressive behaviors. Aromatase, enzyme responsible for conversion of androgens to estrogens, is expressed at high levels early development both male female cortices, suggesting a brain-synthesized estrogens corticogenesis. This study investigated how local synthesis affects neurodevelopment cerebral cortex, this differs males...