Part of the Basic Biomedical and Physiological Science research group and the Neuroscience and Molecular Psychiatry research group, this group, led by Dr Andrew Coogan, is interested in attempting to delineate some of the molecular, neurophysiological and anatomical factors that underpin the circadian timekeeping system in mammals.

Circadian rhythms are recurring patterns in various physiological parameters that display periods of about 24 hours. In other words, these are things we tend to do at the same time every day. Examples of circadian rhythms are the sleep/wake cycles, feeding schedules, cycles in body temperature and endocrine factors (e.g. cortisol, prolactin). Circadian timekeeping mechanisms are deployed by organisms from cyanobacteria up the evolutionary scale, through yeast, fungi and rodents, to humans. Thus, circadian clocks can be regarded as a key homeostatic control mechanism, one that allows an organism to anticipate changes in its environment, and not merely react to those changes.

In mammals, it is known that the circadian system is a highly distributed one, with several organs expressing molecular components of the circadian clock. Part of the hypothalamus of the brain, the suprachiasmatic nucleus, is known to be the site of the master circadian clock, which in turn integrates environmental stimuli (e.g. light) and synchronises the phase of clocks present in other brain sites and peripheral organs. It is not clear how the communication between the master suprachismatic clock and the other constituent components is achieved, although it seems likely that a mix of hard-wired neuronal connections and humeral factors are involved.

In recent years, it has become evident that dysfunction of the circadian clock is an important factor in various disease. For example, there is circadian control of the cell cycle, and circadian clock genes (e.g. Per2) act as tumour suppressor and the expression of these genes is aberrant in cancer. Likewise, there is a body of evidence that implicated circadian rhythm dysfunction in various psychiatric disorders (schizophrenia, bipolar disorder, ADHD). Furthermore, the functionality of the circadian clock declines with normal ageing, and it is believed that these changes lead to decreased quality of sleep in the elderly.

This group is addressing a number of these issues, using a mix of molecular, electrophysiological, endocrine and behavioural techniques in order to gain a better insight into clock function in health and disease. Current projects include:

• Assessing the expression of neuroimmune mediators in the circadian clock, in order to assess the cross talk between the immune system and the clock and gain insight regarding sleep and behavioural disturbance in the medically ill
• Addressing how the circadian system changes with increasing age, in particular how communication between disparate components of the system may become altered in senescence
• Asking how the circadian clock may be perturbed in ADHD and whether this contributes to the psychopathology of the condition (in collaboration with Professor Thome)
• Investigating the contribution of MAP kinase signalling to the normal running of the suprachismatic clock

There are close links with the neuroscience groups of Professor Rees and Professor Thome, as well as with a number of other laboratories.

Academic Staff
Dr Andrew Coogan

Publications
Schneider M, Retz W, Coogan AN, Thome J, Rosler M (2006) Anatomical and fuctional brain imaging in adult attention-deficit/hyperactivity disorder (ADHD) – a neurological view. Eur. Arch. Psychiatry Clin. Neurosci. 256: I/32 – I/41.

Coogan AN, Piggins HD Daytime dark pulse suppress levels of c-Fos and P-ERK in the hamster suprachiasmatic nucleus. (2005) Eur. J. Neurosci. 22: 158-168.

Coogan AN, Piggins HD MAP kinases in the mammalian circadian system: key regulators of clock function. (2004) J. Neurochem. 90: 769-775.

Hughes AT, Fahey B, Cutler DJ, Coogan AN, Piggins HD Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor. (2004) J Neurosci. 24:3522-6.

Coogan AN, Piggins HD Circadian and Photic regulation of phosphorylation of ERK1/2 and Elk-1 in the suprachiasmatic nuclei of the Syrian hamster. (2003) J. Neurosci. 23: 3085-3093.

Piggins HD, Samuels RE, Coogan AN, Cutler DJ Distribution of of substance P and neurokinin-1 receptor immunoreactivity in the suprachiasmatic nuclei and intergeniculate leaflet of hamster, mouse,and rat. (2001) J. Comp. Neurol. 438: 50-65.

Coogan AN, Rawlings N, Luckman SM, Piggins HD Effects of neurotensin on discharge rates of rat suprachiasmatic nucleus neurons in vitro. (2001) Neuroscience 103: 663-672.

Piggins HD, Coogan AN, Cutler DJ, Reed HE Neurochemistry of the circadian clock. 164-180. in Biological Rhythms, ed. V. Kumar, Narosa, New Delhi.

McArthur AJ, Coogan AN, Supaporn L, Sugden D, Biello SM, Piggins HD Gastrin-releasing peptide phase shifts rodent SCN rhythms in vitro. (2000) J. Neuroscience 20:5496-5502.

O’Connor JJ, Coogan AN Actions of the pro-inflammatory cytokine IL-1 on central synaptic transmission. (1999) Expt. Physiol. 84: 601-614.

Coogan AN, O’Connor JJ Interleukin-1beta; inhibits a tetraethylammonium-induced synaptic potentiation in the rat dentate gyrus in vitro. (1999) Eur. J. Pharmacol. 374: 197-206.

Coogan AN, O’Neill LAJ, O’Connor JJ The p38 mitogen-activated protein kinase inhibitor SB203580 antagonises the inhibitory effects of interleukin-1 on long-term potentiation in the rat dentate gyrus in vitro. (1999) Neuroscience 93: 57-69.

Coogan AN, O’Leary DM, O’Connor, JJ p42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic plasticity in rat dentate in vitro. (1999) J. Neurophysiol. 81: 103-110.

Coogan A, O’Connor, JJ Inhibition of NMDA receptor-mediated syanptic transmission in the rat dentate gyrus in vitro by IL-1. (1997) Neuroreport 8: 2107-2110.

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