OPA1 and cardiolipin team up for mitochondrial fusion

Fusion between the inner membranes of two mitochondria requires the GTPase optic atrophy 1 (OPA1), but the molecular mechanism is poorly understood. A study now shows that fusion of two liposomes can be performed by OPA1 tethered to just one liposome, through an interaction with the phospholipid cardiolipin on the opposing liposome

Changes in the distribution of the neuron-specific B-50, neurofilament protein and glial fibrillary acidic proteins following an unilateral mesencephalic lesion in the rat

Following a unilateral electrolytic lesion in the ventral rat mesencephalon, changes in the immunocytochemical distribution of the neuron-specific B-50, neurofilament (NF) protein and glial fibrillary acidic (GFAP) proteins were studied around the lesion after 0, 3, 10 and 28 days. At all recovery times, the controls displayed on immunostaining with anti-B-50 and anti-neurofilament antibodies, a characteristic pattern of synaptic and neuritic localization of these antigens, whereas anti-GFAP staining revealed a distribution typical for astrocytes. The lesion was characterized by a center of coagulated material that exhibited immunoreactivity to B-50 (BIR) and NF (NFIR), but never GFAP-immunoreactivity. From 3 days on, the center became surrounded by disintegrating cells which were unreactive to the antibodies. The antigen distribution changed temporally, predominantly at the lesion rim. By 10 and 28 days postlesion, additional BIR was observed as punctuate dots in fibers and membranes of neurons. Enhanced NFIR was detected in fibers and cell bodies. Many astrocytes were detected around the lesion rim, forming by 28 days postsurgery a barrier between the lesion cavity and the uninjured tissue. Our study shows that distribution changes in B-50, NF and GFAP around the lesion may indicate local degenerative and adaptative processes as a temporal response to brain trauma

Changes in properties and neurosteroid regulation of GABAergic synapses in the supraoptic nucleus during the mammalian female reproductive cycle

GABAA receptor-mediated synaptic innervation of oxytocin neurones in the supraoptic nucleus (SON) was analysed in adult female rats going through their first reproductive cycle by recording the spontaneous inhibitory postsynaptic currents (sIPSCs) at six stages of female reproduction.During pregnancy we observed a reduction in the interval between monoquantal sIPSCs. The synaptic current amplitude, current decay and neurosteroid sensitivity of postsynaptic GABAA receptors observed at this stage were not distinguishable from those measured in virgin stage SON.Upon parturition an increase in monoquantal synaptic current decay occurred, whereas potentiation by the progesterone metabolite allopregnanolone (3α-OH-DHP) was suppressed.Throughout a substantial part of the lactation period the decay of synaptic currents remained attenuated, whilst the potentiation by 3α-OH-DHP remained suppressed.Several weeks after the end of lactation sIPSC intervals, their current decay velocity as well as the potentiation by 3α-OH-DHP were restored to pre-pregnancy levels, which is indicative of the cyclical nature of synaptic plasticity in the adult SON.Competitive polymerase chain reaction (PCR) analysis showed that virgin animals expressed α1 and α2 GABAA receptor subunit mRNA at a relative ratio of 2 : 1 compared with β-actin. After pregnancy both α1 and α2 subunit mRNA levels were transiently increased, although at a relative ratio of 1 : 4, in line with the hypothesis that α2 plays a large role in postsynaptic receptor functioning. During post-lactation both α subunits were downregulated.We propose that synaptic remodelling in the SON during pregnancy includes changes in the putative number of GABA release sites per neurone. At parturition, and during the two consecutive weeks of lactation, a subtype of postsynaptic GABAA receptors was observed, distinct from the one being expressed before and during pregnancy. Synaptic current densities, calculated in order to compare the impact of synaptic inhibition, showed that, in particular, the differences in 3α-OH-DHP potentiation of these two distinct GABAA receptor subtypes produce robust shifts in the impact of synaptic inhibition of oxytocin neurones at the different stages of female reproduction