title: Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory.
abstract: The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino acid-starved cells have reported that glutamine addition can either stimulate or repress mTORC1 activity, depending on the particular experimental system that was used. However, these experiments do not directly address the effect of glutamine on mTORC1 activity under physiological conditions in nondeprived cells in vivo. We present experimental results indicating that intrahippocampal administration of glutamine to rats reduces mTORC1 activity. Moreover, post-training administration of glutamine impairs long-term spatial memory formation, while coadministration of glutamine with leucine had no influence on memory. Intracellular recordings in hippocampal slices showed that glutamine did not alter either excitatory or inhibitory synaptic activity, suggesting that the observed memory impairments may not result from conversion of glutamine to either glutamate or GABA. Taken together, these findings indicate that glutamine can decrease mTORC1 activity in the brain and may have implications for treatments of neurological diseases associated with high mTORC1 signaling.
authors: Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
authors: Natalia S
authors: NS
authors: Rozas
authors: Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
authors: John B
authors: JB
authors: Redell
authors: Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
authors: Juan D
authors: JD
authors: Pita-Almenar
authors: Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA.
authors: James
authors: J
authors: Mckenna
authors: Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
authors: Anthony N
authors: AN
authors: Moore
authors: Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA.
authors: Michael J
authors: MJ
authors: Gambello
authors: Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA p.dash@uth.tmc.edu.
authors: Pramod K
authors: PK
authors: Dash
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005973:Glutamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D057567:Memory, Long-Term / Q000187:drug effects*; D046912:Multiprotein Complexes / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects*; D065852:Spatial Memory / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D005973:Glutamine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007930:Leucine