Non-neuronal BDNF, a key player in development of central sensitization and neuropathic pain

status: publishe

Water-seeking behavior in insects harboring hairworms: should the host collaborate?

We explored the idea that hosts infected with manipulative parasites might mitigate the costs of infection by collaborating with the parasite rather than resisting it. Nematomorphs are usually considered to be manipulative parasites of arthropods because they cause hosts to seek an aquatic environment, which is needed by the adult parasite. We placed infected cricket hosts in situations of forced noncompliance and compared some fitness parameters (life expectancy, gonad development, and reproductive behaviors) in noncompliant hosts and hosts allowed to express parasite-induced behavior. Compared to uninfected controls, reduced survival was observed in both males and females from the two categories of infected hosts, collaborative or not. A substantial proportion of collaborative females produced eggs or had developed ovaries while such phenomena were never observed among noncollaborative ones. Collaborative females retained a nymphal phenotype, but adult males nevertheless courted and produced spermatophores to such females. However, collaborative females had difficulties mounting males, taking spermatophores and/or ovipositing. In contrast to females, all males were entirely castrated by the parasite regardless of their behavior, collaborative or not. Thus, bringing the parasite into water does not effectively mitigate the costs of infection for the host. Copyright 2005.host collaboration; host manipulation; Nematomorpha; Orthoptera

The Ca(2+)-activated cation channel TRPM4 is a negative regulator of angiotensin II-induced cardiac hypertrophy

Cardiac muscle adapts to hemodynamic stress by altering myocyte size and function, resulting in cardiac hypertrophy. Alteration in myocyte calcium homeostasis is known to be an initial signal in cardiac hypertrophy signaling. Transient receptor potential melastatin 4 protein (TRPM4) is a calcium-activated non-selective cation channel, which plays a role in regulating calcium influx and calcium-dependent cell functions in many cell types including cardiomyocytes. Selective deletion of TRPM4 from the heart muscle in mice resulted in an increased hypertrophic growth after chronic angiotensin (AngII) treatment, compared to WT mice. The enhanced hypertrophic response was also traceable by the increased expression of hypertrophy-related genes like Rcan1, ANP, and α-Actin. Intracellular calcium measurements on isolated ventricular myocytes showed significantly increased store-operated calcium entry upon AngII treatment in myocytes lacking the TRPM4 channel. Elevated intracellular calcium is a key factor in the development of pathological cardiac hypertrophy, leading to the activation of intracellular signaling pathways. In agreement with this, we observed significantly higher Rcan1 mRNA level, calcineurin enzyme activity and protein level in lysates from TRPM4-deficient mice heart compared to WT after AngII treatment. Collectively, these observations are consistent with a model in which TRPM4 is a regulator of calcium homeostasis in cardiomyocytes after AngII stimulation. TRPM4 contributes to the regulation of driving force for store-operated calcium entry and thereby the activation of the calcineurin-NFAT pathway and the development of pathological hypertrophy.status: publishe

TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis

In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this process. TRPM4 is expressed in mouse and human neuronal somata, but it is also expressed in axons in inflammatory CNS lesions in experimental autoimmune encephalomyelitis (EAE) in mice and in human multiple sclerosis tissue. Deficiency or pharmacological inhibition of TRPM4 using the antidiabetic drug glibenclamide resulted in reduced axonal and neuronal degeneration and attenuated clinical disease scores in EAE, but this occurred without altering EAE-relevant immune function. Furthermore, Trpm4(-/-) mouse neurons were protected against inflammatory effector mechanisms such as excitotoxic stress and energy deficiency in vitro. Electrophysiological recordings revealed TRPM4-dependent neuronal ion influx and oncotic cell swelling upon excitotoxic stimulation. Therefore, interference with TRPM4 could translate into a new neuroprotective treatment strategy