Hypothalamic gonadotropin-releasing hormone (GnRH) is a key hormone for reproductive functions in vertebrates and non-vertebrates. Although GnRH neuronal system is regulated by several factors such as steroids, neurotransmitters and neuropeptides, it is not fully understood how environmental signals control the GnRH neuronal system. RFamide peptides, members of peptides possessing an Arg-Phe-NH(2) motif at their C-terminus, have recently been characterized as major regulators of GnRH neurons. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH), are emerging as important regulators of the reproductive axis. Kisspeptin acts as the accelerator, directly driving GnRH neurons, whereas GnIH acts as the restraint. In addition, other RFamide peptides such as prolactin-releasing peptide (PrRP), PQRFa peptide, 26RFa/QRFP are also known to control reproduction. These RFamide peptides are regulated by environmental factors such as photoperiods, steroid hormones, metabolic signals, and stress. How environmental signals are integrated by RFamide peptides to regulate reproduction through the GnRH neurons?
Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy.