[AVX Seminar] Free radical brain communication and cognition: function and failure during aging and neurodegeneration

AVX Seminar

Title: Free radical brain communication and cognition: function and failure during aging and neurodegeneration

Speaker: João Laranjinha

Affiliation: Faculty of Pharmacy, University of Coimbra, Center for Neurosciences and Cell Biology, University of Coimbra

Abstract:

Appreciation is growing that free radicals and oxidants, notably nitric oxide (·NO), are cellular messengers involved in the redox regulation of cell process, supporting brain functions. This notion opposes an impression from the past that all free radicals are merely highly reactive and highly damaging to biological systems.

Neuronal activation at glutamatergic synapses leads to the synthesis of ·NO by nitric oxide synthases and it is clear that ·NO does not act like a traditional neurotransmitter; it is not stored in vesicles, does not reacts specific with membrane receptors and it does not follow a simple, one-way conduction across synapses. Nitric oxide acts via volume signaling, targeting remote cells, (neurons, astrocytes, vascular cells …), regardless of whether these cells are connected to each other. Such a property provides a high degree of plasticity and versality required for the neurochemistry of brain functions, as in learning and cognition.

The brain is uniquely dependent on a constant and well-regulated amount of blood flow. In view of the limited energy availability, the brain is equipped with fine mechanisms for a precise spatial and temporal control of cerebral blood flow according to cellular activity, thus providing active neurons with bioenergetic substrates. This process, neurovascular coupling, is critical for cognition and failure in neurovascular coupling, either during aging and disease (e.g., Alzheimer´s disease ), compromises brain integrity and functionality. The regulation of neurovascular coupling is under the concerted cooperation of the cells comprising the neurovascular unit but the role of ·NO is central to convey the message from neurons to nearby blood vessels. Multimodal and molecular mechanistic approaches in vivo have spotted the early dysfunction of neurovascular coupling as a central event in cognition impairment and that diet, via redox cycles of nitrite with polyphenols and ascorbate, increases ·NO bioavailability and augments cerebral blood flow in hippocampus, thus suggesting a role of diet on cognitive enhancement in aging and neurodegeneration.