A5030666031- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- ATP Synthase and ATPases Research
- Trace Elements in Health
- Heavy Metal Exposure and Toxicity
- Immune Response and Inflammation
- Vestibular and auditory disorders
- Alzheimer's disease research and treatments
- Cytokine Signaling Pathways and Interactions
- S100 Proteins and Annexins
- Receptor Mechanisms and Signaling
- RNA modifications and cancer
- Regulation of Appetite and Obesity
- Nerve injury and regeneration
- RNA regulation and disease
- Genetic and Kidney Cyst Diseases
- Traumatic Brain Injury and Neurovascular Disturbances
- Pancreatic function and diabetes
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience of respiration and sleep
- Neurotransmitter Receptor Influence on Behavior
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
Universitat Autònoma de Barcelona
2015-2025
North-West University
2023-2025
University of Washington
2010-2019
Seattle University
2019
Howard Hughes Medical Institute
2011-2017
Seattle Children's Hospital
2016
Laboratoire de Biochimie
2015
Developmental Studies Center
2015
The University of Sydney
2009
Zero to Three
2008
Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated neurodegenerative disease. Here, we find that a key consequence of ROS neuronal dysfunction is the accumulation lipid droplets (LD) glia. In Drosophila, triggers c-Jun-N-terminal Kinase (JNK) Sterol Regulatory Element Binding Protein (SREBP) activity leading to LD glia prior or at onset neurodegeneration. The accumulated lipids peroxidated presence ROS. Reducing peroxidation via targeted lipase overexpression...
More from mTOR Leigh syndrome is a rare, untreatable, inherited neurodegenerative disease in children that caused by functional disruption of mitochondria, the cell's energy-producing organelles. Johnson et al. (p. 1524 , published online 14 November; see Perspective Vafai and Mootha ) show rapamycin, drug used clinically as an immunosuppressant for treatment certain cancers, delayed onset progression neurological symptoms mouse model significantly extended survival animals. Rapamycin...
To explore the lethal, ataxic phenotype of complex I deficiency in Ndufs4 knockout (KO) mice, we inactivated selectively neurons and glia (NesKO mice). NesKO mice manifested same symptoms as KO including retarded growth, loss motor ability, breathing abnormalities, death by ~7 wk. Progressive neuronal deterioration gliosis specific brain areas corresponded to behavioral changes disease advanced, with early involvement olfactory bulb, cerebellum, vestibular nuclei. Neurons, particularly these...
In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a tether that interacts with an unknown partner on the endoplasmic reticulum (ER). this work, we identified MFN2 splice variant ERMIT2 ER tethering of MFN2. Splicing produced and ERMIN2, two ER-specific variants. ERMIN2 regulated morphology, whereas localized ER-mitochondria interface interacted mitochondrial mitofusins to mitochondria. This allowed...
Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with gliosis in several brain regions that usually results infantile death. Loss of murine Ndufs4, which encodes NADH dehydrogenase (ubiquinone) iron-sulfur protein 4, compromised activity mitochondrial complex I as well progressive neurodegenerative and behavioral changes resemble LS. Here, we report the development breathing abnormalities model Magnetic resonance imaging revealed hyperintense bilateral lesions dorsal stem...
Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny these critical hypothalamic is largely unknown. We developed a novel approach to examine developmental pathways that link specific subtypes neurons by combining embryonic adult ribosome-tagging strategies in mice. This new method shows Pomc -expressing precursors not only differentiate into discrete mediate balance (POMC AgRP neurons), but also for puberty onset...
Abstract Ribosome tagging has become a very useful in vivo approach for analyzing gene expression and mRNA translation specific cell types that are difficult time consuming to isolate by conventional methods. The is based on selectively expressing hemagglutinin A (HA)–tagged ribosomal protein target type then using antibodies against HA purify the polysomes associated mRNAs from cell. original makes use of mouse line (RiboTag) harboring modified allele Rpl22 ( Rpl22‐HA ) induced action Cre...
Abstract We examined metallothionein (MT)‐induced neuroprotection during kainic acid (KA)‐induced excitotoxicity by studying transgenic mice with MT‐I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed inflammation delayed brain damage. show for the first time that even though TgMT were more susceptible to KA, cerebral decreases neuronal degeneration cell death as measured 3 days after administration. Hence, proinflammatory responses of...
Abstract IL-6 is crucial for the induction of many murine models autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis. To establish role site-specific production in autoimmunity, we examined myelin oligodendrocyte glycoprotein immunization-induced EAE transgenic mice (GFAP-IL6) with restricted to cerebellum. Myelin glycoprotein-immunized (Mi-) GFAP-IL6 developed severe ataxia but no physical signs spinal cord involvement, which was sharp...
Male spermatogenesis is a complex biological process that regulated by hormonal signals from the hypothalamus (GnRH), pituitary gonadotropins (LH and FSH) testis (androgens, inhibin). The two key somatic cell types of testis, Leydig Sertoli cells, respond to androgens regulate development maturation fertilization competent spermatozoa. Although progress has been made in identification specific transcripts are translated cells their response hormones, efforts expand these studies have...
Abstract Action control is a key brain function determining the survival of animals in their environment. In mammals, neurons expressing dopamine D2 receptors (D2R) dorsal striatum (DS) and nucleus accumbens (Acb) jointly but differentially contribute to fine regulation movement. However, region-specific molecular features are presently unknown. By combining RNAseq striatal D2R histological analyses, we identified hundreds novel markers, which may serve as tools target selective...
Anesthetics are in routine use, yet the mechanisms underlying their function incompletely understood. Studies vitro demonstrate that both GABAA and NMDA receptors modulated by anesthetics, but whole animal models have not supported role of these as sole effectors general anesthesia. Findings C. elegans children reveal defects mitochondrial complex I can cause hypersensitivity to volatile anesthetics. Here, we tested a knockout (KO) mouse with reduced due inactivation Ndufs4 gene, which...
Signaling through N-methyl-D-aspartate-type glutamate receptors (NMDARs) is essential for the development of behavioral sensitization to psychostimulants such as amphetamine (AMPH). However, cell type and brain region in which NMDAR signaling required AMPH remain unresolved. Here we use selective inactivation Grin1, gene encoding NR1 subunit NMDARs, dopamine neurons or their medium spiny neuron (MSN) targets, address this issue. We show that not AMPH. Conversely, removing NMDARs from MSNs...
Mitochondrial deficits in energy production cause untreatable and fatal pathologies known as mitochondrial disease (MD). Central nervous system affectation is critical Leigh Syndrome (LS), a common MD presentation, leading to motor respiratory deficits, seizures premature death. However, only specific neuronal populations are affected. Furthermore, their molecular identity contribution the remains unknown. Here, using mouse model of LS lacking complex I subunit Ndufs4, we dissect role...
Background: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute secondary tissue degeneration.We previously reported that this due, in part, the low levels of anti-inflammatory cytokines, such as IL-4.Since IL-13 IL-4 share receptors both cytokines drive microglia towards an vitro, here we studied whether administration SCI leads beneficial effects.Methods: We injected mice with recombinant or at 48 h assessed their...
Leigh syndrome is a mitochondrial disease characterized by neurodegeneration, neuroinflammation, and early death. Mice lacking NDUFS4, complex I subunit (Ndufs4 KO mice), have been established as good animal model for studying human pathology associated with syndrome. As the progresses, there an increase in neurodegeneration thereby leading to deteriorating neurological symptoms, including motor deficits, breathing alterations, eventually, death of animal. However, despite magnitude...