TGI Friday! Our weekly round-up of recently published research abstracts and related items | 18 July 2014

From the European Journal of Neuroscience, 5 July 2014/

Induction of interleukin-1β by activated microglia is a prerequisite for immunologically induced fatigue

Masataka Ifuku(1), Shamim M. Hossain(1), Mami Noda(2) and Toshihiko Katafuchi(1)
1) Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
2) Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
* Correspondence: Dr T. Katafuchi, as above.
E-mail: kataf@physiol.med.kyushu-u.ac.jp

Abstract

We previously reported that an intraperitoneal (i.p.) injection of synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly-I:C), produced prolonged fatigue in rats, which might serve as a model for chronic fatigue syndrome.

The poly-I:C-induced fatigue was associated with serotonin transporter (5-HTT) overexpression in the prefrontal cortex (PFC), a brain region that has been suggested to be critical for fatigue sensation.

In the present study, we demonstrated that microglial activation in the PFC was important for poly-I:C-induced fatigue in rats, as pretreatment with minocycline, an inhibitor of microglial activation, prevented the decrease in running wheel activity. Poly-I:C injection increased the microglial interleukin (IL)-1β expression in the PFC.

An intracerebroventricular (i.c.v.) injection of IL-1β neutralising antibody limited the poly-I:C-induced decrease in activity, whereas IL-1β (i.c.v.) reduced the activity in a dose-dependent manner. 5-HTT expression was enhanced by IL-1β in primary cultured astrocytes but not in microglia. Poly-I:C injection (i.p.) caused an increase in 5-HTT expression in astrocytes in the PFC of the rat, which was inhibited by pretreatment with minocycline (i.p.) and rat recombinant IL-1 receptor antagonist (i.c.v.).

Poly-I:C injection (i.p.) led to a breakdown of the blood–brain barrier and enhanced Toll-like receptor 3 signaling in the brain. Furthermore, direct application of poly-I:C enhanced IL-1β expression in primary microglia.

We therefore propose that poly-I:C-induced microglial activation, which may be at least partly caused by a direct action of poly-I:C, enhances IL-1β expression. Then, IL-1β induces 5-HTT expression in astrocytes, resulting in the immunologically induced fatigue.


From the Handbook of Clinical Neurology, published by Elsevier, 2014.

Human herpesvirus 6 and the nervous system

Hill JA(1), Venna N(2).
1) Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA. Electronic address: joshuaah@uw.edu.
2) Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

Abstract

Human herpesvirus (HHV)-6 is a β-herpesvirus that infects most infants by 2 years of age and persists in a variety of host cells after primary infection, with intermittent reactivation typically during periods of immunosuppression.

HHV-6 has two closely related species, HHV-6A and B, which are both neurotropic and can be detected in up to 85% of brain samples at autopsy.

This pleiotropic virus has been implicated in many central nervous system (CNS) diseases, including febrile seizures (FS), epilepsy due to medial temporal lobe sclerosis, multiple sclerosis, encephalomyelitis, progressive multifocal leukoencephalopathy, chronic fatigue syndrome, and cognitive dysfunction.

The significance of HHV-6 infection is often controversial due to the challenge implicit in attributing disease to a commensal virus of the brain. Studies have used a variety of unstandardized techniques on an array of sample sources to detect HHV-6, making direct comparisons problematic.

In addition, many detection methods do not distinguish between latent and active infection. However, there is accumulating evidence implicating HHV-6 as a cause of CNS pathology, especially in FS and encephalitis.

Treatment options are limited, fraught with side-effects, and poorly studied. Whether HHV-6 is a commensal pathogen of the brain, marker of immune dysregulation, trigger of autoimmunity, or directly neurotoxic mediator of CNS disease will remain uncertain for many CNS diseases until more refined studies are performed.


From Frontiers in Physiology, 8 July 2014. Full text available at link.

Review ARTICLE

Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome

Elisabeth Lambert and Gavin W. Lambert
BakerIDI Heart and Diabetes Institute, Australia

Orthostatic intolerance is the inability to tolerate the upright posture and is relieved by recumbence. It most commonly affects young women and has a major impact on quality of life and psychosocial well being.

Several forms of orthostatic intolerance have been described.

The most common one is the recurrent vasovagal syncope (VVS) phenotype which presents as a transient and abrupt loss of consciousness and postural tone that is followed by rapid recovery. Another common type of orthostatic intolerance is the postural orthostatic tachycardia syndrome (POTS) which is characterized by an excessive rise in heart rate upon standing and is associated with symptoms of pre syncope such as light-headedness, fatigue, palpitations and nausea.

Maintenance of arterial pressure under condition of reduced central blood volume during the orthostasis is accomplished in large part through sympathetic efferent nerve traffic to the peripheral vasculature.

Therefore sympathetic nervous system (SNS) dysfunction is high on the list of possible contributors to the pathophysiology of orthostatic intolerance. Investigations into the role of the SNS in orthostatic intolerance have yielded mixed results. This review outlines the current knowledge of the function of the SNS in both VVS and POTS.


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