Browse/search for people

Professor Astrid Linthorst

Professor Astrid Linthorst

Professor Astrid Linthorst
Ph.D.(Utrecht)

Professor of Neuroscience and Deputy Head of School

Area of research

Neurochemistry and neuroendocrinology of stress and behaviour

Office Room 2.14
1-5 Whiteladies Road,
BS8 1NU
(See a map)

+44 (0) 117 331 3140
+44 (0) 117 42 83138

Summary

My research group investigates neurochemical and neuroendocrine mechanisms in the brain that support coping with stress. We have a particular interest in the role of GABA and serotonin in the regulation of the neuroendocrine and behavioural responses to stress. We recently characterised the role of synaptic and extrasynaptic GABA transporters in the regulation of extracellular GABA which is of importance for improved understanding of tonic inhibition by GABA in the brain. We also found that stress changes GABAergic neurotransmission in a stressor-dependent manner in the hippocampus, a brain region of critical importance in the stress response.

In another line of research we are studying the distinct regulation of free glucocorticoid hormone levels under baseline and stress conditions. In the blood, glucocorticoids are largely bound to plasma proteins and the concentration of free hormone is very low. However, given that only the free fraction of glucocorticoid hormone is biologically active, it is crucial to study its regulation. We recently discovered that free glucocorticoid hormone responses to stress are 20-30 min delayed compared to the responses of total hormone. The cause of this phenomenon is a rapid, within 5 minutes, release of corticosteroid-binding globulin (CBG) from the liver. This delay will have an important impact on glucocorticoid hormone-mediated responses to stress both in peripheral tissues and in the brain. We are therefore currently investigating the mechanisms underlying the rapid stress-induced release of CBG.

Exercise has been found to improve coping with stress and is regularly used in the treatment of stress-related psychiatric disorders such as depression and anxiety. We are currently investigating the effects of exercise on GABAergic neurotransmission and on the regulation of free glucocorticoid hormone. This research includes studies on extracellular GABA, GABA transporters and synthesising enzymes, and epigenetic changes in promoter regions of selected genes.

Finally, we have recently established a method to measure free cortisol levels in human volunteers by in vivo microdialysis. Our method allows continuous collection of dialysate samples over several days while the volunteer is ambulant. This new approach will allow us to study the levels, circadian rhythms and stress responses of free glucocorticoid hormone in human volunteers and in patient populations.

Our research is currently funded by the Wellcome Trust and the European Union.

Activities / Findings

  • The regulation of extracellular GABA in the hippocampus by serotonin and endocannabinoids
  • Role of GAT-1 and GAT-3 in the regulation of extracellular GABA
  • The effects of voluntary exercise on HPA axis regulation and GABAergic neurotransmission
  • Ultradian rhythm of free corticosterone in brain and peripheral tissue
  • Delayed response of free corticosterone to acute stress caused by a rapid release of CBG from the liver
  • Establishment of microdialysis for glucocorticoid hormones in ambulant humans

Teaching

I am the Course Director of the MSc Molecular Neuroscience (Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology; Faculty of Medicine and Dentistry).

I am Deputy Course Director of the MRes Systems Neuroscience (BBSRC Master Training Grant to Professor Richard Apps and Professor Astrid Linthorst).

Unit Head Foundations of Neuroscience.

Unit Head Principles in Neuroscience.

Various lectures on neuroscience; research methods; statistics.

Keywords

  • Serotonin
  • Noradrenaline
  • GABA
  • Corticosterone
  • Corticotropin-releasing factor
  • Hypothalamic-Pituitary-Adrenocortical (HPA) axis
  • Autonomic Nervous System
  • Hippocampus
  • Exercise
  • In Vivo Microdialysis

Skills

  • Major depression
  • Anxiety
  • Panic Disorder
  • Neuroendocrine disorders

Processes and functions

  • Neurotransmission
  • Neuroendocrine regulation
  • Autonomic regulation
  • Epigenetics
  • Behaviour

Methodologies

  • Microdialysis
  • HPLC with electrochemical detection
  • Behavioural models
  • Radioimmunoassays
  • ELISA's

Expertise

My research group investigates neurochemical and neuroendocrine mechanisms in the brain that support coping with stress. We have a particular interest in the role of GABA and serotonin in the regulation of the neuroendocrine and behavioural responses to stress. Furthermore, we study the distinct regulation of free glucocorticoid levels under baseline and stress conditions. Our research is funded by the BBSRC, Wellcome Trust and Neuroendocrinology Charitable Trust.

  • serotonin
  • noradrenaline
  • GABA
  • stress
  • hypothalamic-pituitary-adrenocortical (HPA) axis
  • autonomic nervous system
  • hippocampus
  • Recent publications

    View complete publications list in the University of Bristol publications system

    Networks & contacts

    • University of Bristol - Professor Johannes (Hans) Reul
    • University of Bristol - Professor Stafford Lightman
    • University of Bristol - Dr Flavie Kersant√© (former postdoc)
    • Riken Brain Science Institute Japan - Professor Alexey Semyanov
    • Institute of Neurology University College London - Professor Matthew Walker
    • Institute of Neurology University College London - Dr Ivan Pavlov

    Edit this profile If you are Professor Astrid Linthorst, you can edit this page. Login required.

    PDF versionDownload PDF