Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans . Using these techniques, we uncover surprising tissue-specific differences in mitochondrial morphology when fusion or fission proteins are absent. From ultrastructural analysis, we reveal a novel role for the fusion protein FZO-1/mitofusin 2 in regulating the structure of the inner mitochondrial membrane. Moreover, we have determined the influence of the individual mitochondrial fission (DRP-1/DRP1) and fusion (FZO-1/mitofusin 1,2; EAT-3/OPA1) proteins on animal behaviour and lifespan. We show that loss of these mitochondrial fusion or fission regulators induced age-dependent and progressive deficits in animal movement, as well as in muscle and neuronal function. Our results reveal that disruption of fusion induces more profound defects than lack of fission on animal behaviour and tissue function, and imply that while fusion is required throughout life, fission is more important later in life likely to combat ageing-associated stressors. Furthermore, our data demonstrate that mitochondrial function is not strictly dependent on morphology, with no correlation found between morphological changes and behavioural defects. Surprisingly, we find that disruption of either mitochondrial fission or fusion significantly reduces median lifespan, but maximal lifespan is unchanged, demonstrating that mitochondrial dynamics play an important role in limiting variance in longevity across isogenic populations. Overall, our study provides important new insights into the central role of mitochondrial dynamics in maintaining organismal health. Electronic supplementary material The online version of this article (10.1007/s00018-019-03024-5) contains supplementary material, which is available to authorized users.
While advances in neuroscience are helping to improve many aspects of human life, inequalities exist in this field between Africa and more scientifically-advanced continents. Many African countries lack the infrastructure and appropriately-trained scientists for neuroscience education and research. Addressing these challenges would require the development of innovative approaches to help improve scientific competence for neuroscience across the continent. In recent years, science-based non-profit organisations (NPOs) have been supporting the African neuroscience community to build state-of-the-art scientific capacity for sustainable education and research. Some of these contributions have included: the establishment of training courses and workshops to introduce African scientists to powerful-yet-cost-effective experimental model systems; research infrastructural support and assistance to establish research institutes. Other contributions have come in the form of the promotion of scientific networking, public engagement and advocacy for improved neuroscience funding. Here, we discuss the contributions of NPOs to the development of neuroscience in Africa.
The science of the brain and nervous system cuts across almost all aspects of human life and is one of the fastest growing scientific fields worldwide. This necessitates the demand for pragmatic investment by all nations to ensure improved education and quality of research in Neurosciences. Although obvious efforts are being made in advancing the field in developed societies, there is limited data addressing the state of neuroscience in sub-Saharan Africa. Here, we review the state of neuroscience development in Nigeria, Africa's most populous country and its largest economy, critically evaluating the history, the current situation and future projections. This review specifically addresses trends in clinical and basic neuroscience research and education. We conclude by highlighting potentially helpful strategies that will catalyse development in neuroscience education and research in Nigeria, among which are an increase in research funding, provision of tools and equipment for training and research, and upgrading of the infrastructure at hand.
Our findings suggest that calcium mediated toxicity is primary to the cause and progression of Parkinsonism and targeting receptors that primarily modulates calcium reduces the morphological and behavioral deficits in drug induced Parkinsonism. VDR activation was more effective than NMDAR inhibition and a combined intervention. We conclude that targeting VDR is key for controlling calcium toxicity in drug/chemotoxin induced Parkinsonism.
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