ABSTRACT
GIT1, a multifunctional signaling adaptor protein, is implicated in the development of dendritic spines and neuronal synapses. GIT1 forms a signaling complex with PIX, RAC, and PAK proteins that is known to play important roles in brain development. Here we found that Git1-knockout (Git1-/-) mice show a microcephaly-like small brain phenotype, which appears to be caused by reduced neuronal size rather than number. Git1-/- mice also show decreased dendritic spine number without morphological alterations in the hippocampus. Behaviorally, Git1-/- mice show impaired motor coordination and learning and memory. In addition, adult dGit Drosophila mutants show decreased brain size and abnormal morphology of the mushroom body. These results suggest that GIT1 is important for brain development in both rodents and flies.
Subject(s)
Adult , Animals , Humans , Mice , Brain , Dendritic Spines , Diptera , Drosophila , Hippocampus , Invertebrates , Learning , Memory , Microcephaly , Mushroom Bodies , Neurons , Phenotype , Rodentia , Synapses , VertebratesABSTRACT
The mushroom body (MB), a bilateral brain structure possessing about 2000-2500 neurons per hemisphere, plays a central role in olfactory learning and memory in Drosophila melanogaster. Extensive studies have demonstrated that three major types of MB neurons (α/β, α'/β' and Γ) exhibit distinct functions in memory processing, including the critical role of approximately 1000 MB α/β neurons in retrieving long-term memory. Inspired by recent findings that MB α/β neurons can be further divided into three subdivisions (surface, posterior and core) and wherein the α/β core neurons play an permissive role in long-term memory consolidation, we examined the functional differences of all the three morphological subdivisions of MB α/β by temporally precise manipulation of their synaptic outputs during long-term memory retrieval. We found the normal neurotransmission from a combination of MB α/β surface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory, whereas output from MB α/β posterior or core subdivision alone is dispensable. These results imply a specific requirement of about 500 MB α/β neurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MB α/β region.
Subject(s)
Animals , Adenylyl Cyclases , Metabolism , Drosophila Proteins , Metabolism , Drosophila melanogaster , Cell Biology , Metabolism , Physiology , Memory, Long-Term , Physiology , Mushroom Bodies , Cell Biology , Physiology , Neurons , Cell Biology , Metabolism , Synapses , Metabolism , Transcription Factors , MetabolismABSTRACT
Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.
Subject(s)
Aged , Animals , Humans , Aging , Genetics , Metabolism , Pathology , Amyotrophic Lateral Sclerosis , Genetics , Metabolism , Pathology , Animals, Genetically Modified , Disease Models, Animal , Drosophila melanogaster , Genetics , Metabolism , Gene Expression , Microscopy, Electron, Scanning , Motor Neurons , Metabolism , Pathology , Mushroom Bodies , Metabolism , Pathology , Mutant Proteins , Genetics , Metabolism , Mutation , Photoreceptor Cells, Invertebrate , Metabolism , Pathology , Plasmids , RNA-Binding Protein FUS , Genetics , Metabolism , Recombinant Fusion Proteins , Genetics , Metabolism , Retinal Degeneration , Pathology , TransfectionABSTRACT
Ganoderma lucidum is a functional food and a source of physiologically beneficial medicine. The Ganoderma fungi contained polyphenols, flavonoids, carotenoids, tannins, saponins and some of micro-elements [Cu, Zn, Mg, Mn and Se] as excellent antioxidants. Data showed a content of polyphenols and flavonoids fractions by HPLC. Ganoderma has a high content of kaempherol [14.43 micro g/g] then myricetin and quercetin [9.94 and 9.33 micro g/g, respectively]. The content of cinnamic acid and P-cumaric acid [9.82 and 11.53 micro g/g] were higher than cumarin, O-cumarin [8.88 and 8.44 micro g/g], respectively. Ganoderma protein is rich in cystine and methionine [0.85 and 13.53 g/100g protein], respectively compared with its level in casein [0.33 and 2.59 g/100g protein]. The ratio of arginine: lysine was higher than of methionine: glycine which is used as indication of the ability of plant proteins to lower cholesterol level in blood. The composition of Ganoderma mushroom having a relatively high content of unsaturated fatty acids [oleic, linoleic, linolenic, ecosanoic and decosahexanoic acids]. Also, the reducing power Ganoderma extract was higher compared to that for vitamin C