Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications
Sex differences in brain metabolism and their relationship to neurodegenerative diseases like Alzheimer’s are an important emerging topic in neuroscience. Intrinsic anatomic and metabolic differences related to male and female physiology have been described, underscoring the importance of considerin...
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2024-11-01
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| author | José Manuel Martínez-Martos Vanesa Cantón-Habas Manuel Rich-Ruíz María José Reyes-Medina María Jesús Ramírez-Expósito María del Pilar Carrera-González |
| author_facet | José Manuel Martínez-Martos Vanesa Cantón-Habas Manuel Rich-Ruíz María José Reyes-Medina María Jesús Ramírez-Expósito María del Pilar Carrera-González |
| author_sort | José Manuel Martínez-Martos |
| collection | DOAJ |
| description | Sex differences in brain metabolism and their relationship to neurodegenerative diseases like Alzheimer’s are an important emerging topic in neuroscience. Intrinsic anatomic and metabolic differences related to male and female physiology have been described, underscoring the importance of considering biological sex in studying brain metabolism and associated pathologies. The hippocampus is a key structure exhibiting sex differences in volume and connectivity. Adult neurogenesis in the dentate gyrus, dendritic spine density, and electrophysiological plasticity contribute to the hippocampus’ remarkable plasticity. Glucose transporters GLUT3 and GLUT4 are expressed in human hippocampal neurons, with proper glucose metabolism being crucial for learning and memory. Sex hormones play a major role, with the aromatase enzyme that generates estradiol increasing in neurons and astrocytes as an endogenous neuroprotective mechanism. Inhibition of aromatase increases gliosis and neurodegeneration after brain injury. Genetic variants of aromatase may confer higher Alzheimer’s risk. Estrogen replacement therapy in postmenopausal women prevents hippocampal hypometabolism and preserves memory. Insulin is also a key regulator of hippocampal glucose metabolism and cognitive processes. Dysregulation of the insulin-sensitive glucose transporter GLUT4 may explain the comorbidity between type II diabetes and Alzheimer’s. GLUT4 colocalizes with the insulin-regulated aminopeptidase IRAP in neuronal vesicles, suggesting an activity-dependent glucose uptake mechanism. Sex differences in brain metabolism are an important factor in understanding neurodegenerative diseases, and future research must elucidate the underlying mechanisms and potential therapeutic implications of these differences. |
| format | Article |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-e11a00da74824bf68f832485868c706d2024-12-27T14:35:52ZengMDPI AGLife2075-17292024-11-011412154710.3390/life14121547Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease ImplicationsJosé Manuel Martínez-Martos0Vanesa Cantón-Habas1Manuel Rich-Ruíz2María José Reyes-Medina3María Jesús Ramírez-Expósito4María del Pilar Carrera-González5Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Las Lagunillas University Campus, 23009 Jaen, SpainDepartment of Nursing, Pharmacology and Physiotherapy, Faculty of Medicine and Nursing, University of Córdoba, 14004 Córdoba, SpainDepartment of Nursing, Pharmacology and Physiotherapy, Faculty of Medicine and Nursing, University of Córdoba, 14004 Córdoba, SpainDepartment of Nursing, Pharmacology and Physiotherapy, Faculty of Medicine and Nursing, University of Córdoba, 14004 Córdoba, SpainExperimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Las Lagunillas University Campus, 23009 Jaen, SpainExperimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Las Lagunillas University Campus, 23009 Jaen, SpainSex differences in brain metabolism and their relationship to neurodegenerative diseases like Alzheimer’s are an important emerging topic in neuroscience. Intrinsic anatomic and metabolic differences related to male and female physiology have been described, underscoring the importance of considering biological sex in studying brain metabolism and associated pathologies. The hippocampus is a key structure exhibiting sex differences in volume and connectivity. Adult neurogenesis in the dentate gyrus, dendritic spine density, and electrophysiological plasticity contribute to the hippocampus’ remarkable plasticity. Glucose transporters GLUT3 and GLUT4 are expressed in human hippocampal neurons, with proper glucose metabolism being crucial for learning and memory. Sex hormones play a major role, with the aromatase enzyme that generates estradiol increasing in neurons and astrocytes as an endogenous neuroprotective mechanism. Inhibition of aromatase increases gliosis and neurodegeneration after brain injury. Genetic variants of aromatase may confer higher Alzheimer’s risk. Estrogen replacement therapy in postmenopausal women prevents hippocampal hypometabolism and preserves memory. Insulin is also a key regulator of hippocampal glucose metabolism and cognitive processes. Dysregulation of the insulin-sensitive glucose transporter GLUT4 may explain the comorbidity between type II diabetes and Alzheimer’s. GLUT4 colocalizes with the insulin-regulated aminopeptidase IRAP in neuronal vesicles, suggesting an activity-dependent glucose uptake mechanism. Sex differences in brain metabolism are an important factor in understanding neurodegenerative diseases, and future research must elucidate the underlying mechanisms and potential therapeutic implications of these differences.https://www.mdpi.com/2075-1729/14/12/1547hippocampusAlzheimer’s diseaseglucose transportersGLUT4renin–angiotensin systeminsulin regulated aminopeptidase |
| spellingShingle | José Manuel Martínez-Martos Vanesa Cantón-Habas Manuel Rich-Ruíz María José Reyes-Medina María Jesús Ramírez-Expósito María del Pilar Carrera-González Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications Life hippocampus Alzheimer’s disease glucose transporters GLUT4 renin–angiotensin system insulin regulated aminopeptidase |
| title | Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications |
| title_full | Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications |
| title_fullStr | Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications |
| title_full_unstemmed | Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications |
| title_short | Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications |
| title_sort | sexual and metabolic differences in hippocampal evolution alzheimer s disease implications |
| topic | hippocampus Alzheimer’s disease glucose transporters GLUT4 renin–angiotensin system insulin regulated aminopeptidase |
| url | https://www.mdpi.com/2075-1729/14/12/1547 |
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