The impact of Bdnf gene deficiency to the memory impairment and brain pathology of APPswe/PS1dE9 mouse model of Alzheimer's disease
| Autor: | Marius C. Hoener, Masami Kojima, Susanna Kemppainen, Saara Stavén, Heikki Tanila, Hennariikka Koivisto, Henri Autio, Hanna Antila, Eero Castrén, Lothar Lindemann, Elisa Kärkkäinen, Tomi Rantamäki, Liisa Vesa, Pasi Miettinen, Nina N. Karpova |
|---|---|
| Přispěvatelé: | Neuroscience Center |
| Rok vydání: | 2012 |
| Předmět: |
Male
CELL-SURVIVAL lcsh:Medicine Hippocampus Gene Expression Plaque Amyloid Tropomyosin receptor kinase B Amyloid beta-Protein Precursor Mice Behavioral Neuroscience 0302 clinical medicine Learning and Memory Neurotrophic factors Molecular Cell Biology Tyrosine Kinase Signaling Cascade Neurobiology of Disease and Regeneration lcsh:Science AMYLOID DEPOSITION DECREASED-LEVELS 0303 health sciences Multidisciplinary Brain Signaling Cascades Neurology Medicine Female Alzheimer's disease MESSENGER-RNA Research Article Signal Transduction medicine.medical_specialty Cognitive Neuroscience education Mice Transgenic Environment Hyperkinesis Signaling Pathways Presenilin 03 medical and health sciences PARIETAL CORTEX Alzheimer Disease Memory Internal medicine medicine Presenilin-1 Animals Humans WILD-TYPE Cholinergic neuron Maze Learning Biology 030304 developmental biology Brain-derived neurotrophic factor Memory Disorders business.industry Brain-Derived Neurotrophic Factor NERVE GROWTH-FACTOR lcsh:R Body Weight 3112 Neurosciences medicine.disease Disease Models Animal Endocrinology Nerve growth factor nervous system NEUROTROPHIC-FACTOR lcsh:Q Protein Translation Dementia Molecular Neuroscience business 030217 neurology & neurosurgery Psychomotor Performance CHOLINERGIC NEURONS Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 7, p e68722 (2013) |
| ISSN: | 1932-6203 |
| Popis: | Brain-derived neurotrophic factor (BDNF) importantly regulates learning and memory and supports the survival of injured neurons. Reduced BDNF levels have been detected in the brains of Alzheimer's disease (AD) patients but the exact role of BDNF in the pathophysiology of the disorder remains obscure. We have recently shown that reduced signaling of BDNF receptor TrkB aggravates memory impairment in APPswe/PS1dE9 (APdE9) mice, a model of AD. The present study examined the influence of Bdnf gene deficiency (heterozygous knockout) on spatial learning, spontaneous exploratory activity and motor coordination/balance in middle-aged male and female APdE9 mice. We also studied brain BDNF protein levels in APdE9 mice in different ages showing progressive amyloid pathology. Both APdE9 and Bdnf mutations impaired spatial learning in males and showed a similar trend in females. Importantly, the effect was additive, so that double mutant mice performed the worst. However, APdE9 and Bdnf mutations influenced spontaneous locomotion in contrasting ways, such that locomotor hyperactivity observed in APdE9 mice was normalized by Bdnf deficiency. Obesity associated with Bdnf deficiency did not account for the reduced hyperactivity in double mutant mice. Bdnf deficiency did not alter amyloid plaque formation in APdE9 mice. Before plaque formation (3 months), BDNF protein levels where either reduced (female) or unaltered (male) in the APdE9 mouse cortex. Unexpectedly, this was followed by an age-dependent increase in mature BDNF protein. Bdnf mRNA and phospho-TrkB levels remained unaltered in the cortical tissue samples of middle-aged APdE9 mice. Immunohistological studies revealed increased BDNF immunoreactivity around amyloid plaques indicating that the plaques may sequester BDNF protein and prevent it from activating TrkB. If similar BDNF accumulation happens in human AD brains, it would suggest that functional BDNF levels in the AD brains are even lower than reported, which could partially contribute to learning and memory problems of AD patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|