Learn More
The adipose-derived hormone, leptin, was discovered over 10 years ago, but only now are we unmasking its downstream pathways which lead to reduced energy intake (feeding) and increased energy expenditure (thermogenesis). Recent transgenic models have challenged the long-standing supposition that the hypothalamic arcuate nucleus (Arc) is omnipotent in the(More)
Axonal degeneration is a major cause of permanent neurological deficit in multiple sclerosis (MS). The mechanisms responsible for the degeneration remain unclear, but evidence suggests that a failure to maintain axonal sodium ion homeostasis may be a key step that underlies at least some of the degeneration. Sodium ions can accumulate within axons due to a(More)
Axonal degeneration is a major cause of permanent neurological deficit in multiple sclerosis (MS), but no current therapies for the disease are known to be effective at axonal protection. Here, we examine the ability of a sodium channel-blocking agent, flecainide, to reduce axonal degeneration in an experimental model of MS, chronic relapsing experimental(More)
Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) epsilon or delta can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1epsilon and CK1delta using(More)
Axonal degeneration is a major cause of permanent disability in multiple sclerosis (MS). Recent observations from our and other laboratories suggest that sodium accumulation within compromised axons is a key, early step in the degenerative process, and hence that limiting axonal sodium influx may represent a mechanism for axonal protection in MS. Here we(More)
Twilight is characterised by changes in both quantity ("irradiance") and quality ("colour") of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using(More)
In response to stressful stimuli, cells respond by inducing a set of heat shock (stress) proteins (hsps) that play important roles in repair and protective mechanisms. The present study investigates the expression patterns of Hsp27 and Hsp32 in the adult rat hippocampus following whole body hyperthermia. A pronounced induction of these low-molecular-weight(More)
Inflammatory demyelinating neuropathies such as Guillain-Barre syndrome (GBS) and its animal model, experimental autoimmune neuritis (EAN), are typically acute monophasic diseases of the PNS that can leave affected individuals with permanent disability due primarily to axonal degeneration. The mechanisms underlying the degeneration are not understood, but(More)
The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1epsilon-/-, whereas CK1epsilon(tau/tau) shortened circadian period of behavior in(More)
Heat-shock proteins are induced in response to cellular stress. Although heat-shock proteins are known to function in repair and protective mechanisms, their relationship to critical neural processes, such as synaptic function, has received little attention. Here we investigate whether the major heat-shock protein Hsp70 localizes to the synapse following a(More)