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This study examined how excess Mn affects glutamatergic signaling and neurotransmission in a beta\u2010amyloid mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>APP\/PSEN1 and control mice were exposed to systemic Mn subcutaneously. Gene expression, glutamate clearance dynamics, electroencephalography (EEG) activity, and sleep architecture were analyzed using quantitative polymerase chain reaction (qPCR), Western blot, ex vivo hippocampal slices, and EEG recordings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Mn exposure elevated brain Mn levels and altered glutamate dynamics in both WT and APP\/PSEN1 mice. Wild\u2010type (WT) mice showed faster glutamate clearance, increased spiking, disrupted sleep, and brain wave changes. APP\/PSEN1 mice exhibited slower glutamate clearance, altered gene expression, increased glial fibrillary acidic protein (GFAP), and changes in non\u2013rapid eye movement (NREM) delta and rapid eye movement (REM) alpha power.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Mn exposure altered glutamate clearance and brain activity, particularly in WT mice. APP\/PSEN1 mice showed impaired clearance, limited gene expression changes, and altered EEG patterns, suggesting distinct or pre\u2010existing compensatory mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Manganese exposure significantly alters glutamate clearance dynamics differentially in wild\u2010type and APP\/PSEN1 mouse models of Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Acute manganese treatment disrupts sleep architecture, evidenced by changes in electroencephalography (EEG) patterns and vigilance states.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>APP\/PSEN1 mice exhibit slower glutamate clearance and altered gene expression compared to wild\u2010type mice following manganese exposure.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Distinct brain wave frequency shifts were observed in response to manganese treatment, particularly affecting delta, theta, and alpha rhythms.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Findings suggest a potential exacerbation of excitatory\/inhibitory imbalances due to environmental manganese exposure in Alzheimer's pathology.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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