Cognitive function is known to change during normal aging and in age-related disease such as Alzheimer’s disease. Although the exact cause for age-related cognitive decline is not clear, recent studies suggest that a contribution of disturbed mechanisms of plasticity in cognitive dysfunction during the normal aging process. Neuroplasticity is a fundamental feature of the central nervous system that allows synapses to remember previous activity and bring about plastic changes to fine-tune synaptic action, which is reduced with aging. A decrease in plasticity may change the dynamic interactions between cells in hippocampal networks, causing deficits in the storage and retrieval of information. Deficits in synaptic plasticity have been identified in aged animals; however, the factors affecting synaptic plasticity remain unclear. Mounting evidence implicates caveolin-1 as playing a central role in the modulation of synaptic plasticity.
Now, a new study from researchers at The Scripps Research Institute (TSRI), the Veterans Affairs San Diego Healthcare System (VA) and UC San Diego has shown that increasing a crucial cholesterol-binding membrane protein, called caveolin-1 (Cav-1), in neurons within the brain can improve learning and memory in aged mice. The team state that this is a novel strategy for treating neurodegenerative diseases, and it underscores the importance of brain cholesterol.
Previous studies show that Caveolin-1 is the principal structural component of caveolae and participates in cellular cholesterol homeostasis, molecular transport and transmembrane signaling events. Recently it has been shown that caveolin-1 may act as a modulator of compensatory synaptic plasticity in Alzheimer’s disease. Research has also demonstrated that alterations in caveolin-1 expression coincide with the onset of reactive synaptogenesis during injury-induced synaptic remodeling. Therefore, it is speculated that caveolin-1 may have a lifelong modulatory role in synaptic plasticity and contribute to neurodegenerative disease.
Earlier studies from the lab show that raising Cav-1 levels supported healthy rafts of cholesterol involved in neuron growth and cell signaling; however, it wasn’t clear if this new growth actually improved brain function or memory. The current study shows that by bringing back this protein, cholesterol is returned to the cell membrane, which is very important for forming new synaptic contacts.
The current study focuses on Cav-1 and expands teams’ understanding of neuroplasticity, the ability of neural pathways to grow in response to new stimuli. The researchers delivered Cav-1 directly into a region of the brain known as the hippocampus in adult and aged mice. The lab explain that the hippocampus is a structure thought to participate in formation of contextual memories; for example, if one remembers a past picnic when later visiting a park. Results show that in addition to improved neuron growth, treated mice demonstrated better retrieval of contextual memories, in that they froze in place, indicating fear, when placed in a location where they’d once received small electric shocks.
The team surmise that their findings may be a path toward treating age-related memory loss, and this new understanding of Cav-1 and neuroplasticity could also be relevant to memory loss due to alcohol and drug use. For the future, the researchers are now testing this gene therapy in mouse models of Alzheimer’s disease and plan to study whether they can manipulate Cav-1 in other areas of the brain; expanding it to possibly treat spinal cord injury and traumatic brain injury.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.