Project description:Stimulation of the mouse hindlimb via the sciatic nerve was used to induce contractions for 4 hours to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 + 0.1 g/g body weight) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon completion of the study. An immediate-early growth response was present in the EDL (FOS, JUN, ATF3, MAFK) with a similar but attenuated pattern in the soleus. Transcript profiles showed decreased fast fiber specific mRNA (myosin heavy chains 2A, 2B; troponins T3, I; alpha-tropomyosin, m-creatine kinase) and increased slow transcripts (myosin heavy chain slow/1beta, troponin C, tropomyosin 3gamma) in the EDL. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration or myofiber damage in stimulated vs. control muscles. Several fiber type specific transcription factors (EYA1, TEAD1, NFATc1 and c4, PPARG, PPARGC1alpha and beta, BHLHB2) increased in the EDL along with transcription factors characteristic of embryogenesis (KLF4, SOX17, TCF15, PKNOX1, ELAV). No established in vivo satellite cell markers or the genes activated during our parallel studies of satellite cell proliferation in vitro (CYCLINS A2, B2, C, E1, MyoD) increased in the stimulated muscles. These data indicated that onset of fast to slow phenotype conversion occurred in the EDL within 4 hours of stimulation without satellite cell recruitment or muscle injury but was driven by phenotype specific transcription factors from resident fiber myonuclei including activation of nascent developmental transcriptional programs.
Project description:In the gastropod mollusc Lymnaea stagnalis, insulin-like peptides in the central nervous system (CNS) control behavioral changes associated with an associative learning. We examined the responding molecules in the CNS after insulin administration by protein analysis using comparative quantitative mass spectrometry.
Project description:Microglia constitute the myeloid compartment of the Central Nervous System (CNS). scRNA sequencing was employed to decipher diverse microglia populations and other cell types from the cortex.
Project description:Specific mRNAs are transported from the cell body to synapses where their translation can modify communication of pre-existing synapses and induce formation of new synaptic connections in response to learning. Little is known, however, about the identity of the RNAs that are actively transported and when and how these RNAs are utilized during learning. By focusing on RNAs that are associated with kinesin, a motor protein that transports gene products from the cell body to synapses, we have now applied microarrays and 454 sequencing to identify actively transported RNAs from the Aplysia central nervous system. Using a library prepared from the kinesin complex immunoprecipitated from the central nervous system (CNS), we have identified thousands of unique transcripts, of which ~600 mRNAs were annotated. Two sample comparison: kinesin IP vs. control.
Project description:Infections of the central nervous system (CNS) in humans are on the rise due to changing environmental conditions and increase in vulnerable populations comprised of immunocompromised subjects with primary (genetic) or secondary (acquired) immunodeficiency. Many viruses take the opportunity to invade the CNS by capitalizing on impaired immunity of the host. Here we investigate neuropathogenesis of a rare CNS infection in immunocompromised patients caused by the astrovirus and show that it shares many features with another opportunistic infection of the CNS associated with human immunodeficiency virus. We show that astrovirus infects CNS neurons with a major impact on the brainstem. This leads to disrupted synaptic integrity loss of afferent innervation related to infected neurons and global impairment of both excitatory and inhibitory neurotransmission. In the settings of impaired peripheral adaptive immunity host responses to astrovirus infection are dominated by the microglia-macrophage-phagocytosis axis which may be a common compensatory defense mechanism employed by the CNS against opportunistic infections.
Project description:Treatment for many viral infections of the central nervous system (CNS) remains only supportive. Here we address a remaining gap in our knowledge regarding how the CNS and immune systems interact during viral infection. By examining the regulation of the immune and nervous system processes in a nonhuman primate model of West Nile virus neurological disease, we show that virus infection disrupts the homeostasis of the immune-neural-synaptic axis via induction of pleiotropic genes with distinct functions in each component of the axis. This pleiotropic gene regulation suggests an unintended off-target negative impact of virus-induced host immune responses on the neurotransmission, which may be a common feature of various viral infections of the CNS.
Project description:Microglia are macrophages-like cells in the central nervous system (CNS) harboring important roles such as synaptic organization, phagocytosis of debris and apoptotic cells, and repairing damaged tissue. Microglial function is tightly controlled, but under certain pathological conditions, activated microglia can induce excess inflammation which injure live cells in the CNS. Therefore, suppression of microglia is a fundamental strategy to treat CNS disorders. We have previously shown that the antiepileptic drug levetiracetam (LEV) inhibits microglia activation, but mechanism remains unclear. The purpose of this study is to identify a target of LEV to suppress microglial activity.