New Delhi: Hypertension can start impairing major brain cells responsible for cognition well before blood pressure increases by a measurable amount, according to a study conducted on mice, which can help explain how the condition is a major risk factor for cognitive impairment.
Findings published in the journal Neuron suggest that hypertension may induce early changes in how genes in a brain cell express themselves and could interfere with one’s thinking and memory, researchers from Weill Cornell Medical College said.
The study can provide clues for finding ways through which neurodegeneration — seen in disorders such as Alzheimer’s — could be blocked, they said.
Having high blood pressure has been shown to heighten one’s risk of cognitive impairment, usually seen to precede Alzheimer’s disease and dementia, which are marked by affected decision-making and loss of memory.
However, the reasons behind how hypertension can impact cognition are not understood, the researchers said.
While hypertension medications succeed in lowering blood pressure, brain function shows little or no effects, suggesting that changes to blood vessels could cause damage independently of the elevated pressure associated with hypertension, they added.
“We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice, before blood pressure increased,” said senior author and lead researcher Dr Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute and professor of neuroscience and neurology at Weill Cornell Medical College.
“The bottom line is something beyond the dysregulation of blood pressure is involved,” Iadecola said.
For the study, mice were administered the hormone ‘angiotensin’, which raises blood pressure, mimicking what happens in humans. Different types of brain cells were examined to understand the impacts three days later (before blood pressure increased) and after 42 days (when blood pressure was high, and cognition was affected).
At day three, gene expression dramatically changed in three cell types: endothelial cells, interneurons, and oligodendrocytes, the researchers said.
Endothelial cells that line the inner surface of blood vessels were seen to have aged prematurely due to a lower energy metabolism and higher senescence (aging) markers.
They also observed early signs of a weakening in the blood-brain barrier, known to regulate the flow of nutrients into the brain and keep out harmful molecules.
Interneurons — brain cells that regulate the balance of excitatory and inhibitory nerve signals — were damaged, leading to an imbalance between inhibition and excitation, similarly observed in Alzheimer’s disease, the team said.
Further, oligodendrocytes — which enwrap nerve fibres with the protective myelin sheath — did not properly express genes responsible for their maintenance and replacement.
Without enough oligodendrocytes to maintain the health of the myelin sheath, neurons eventually lose the ability to communicate with each other, which is critical for cognitive function, the researchers said, adding that more changes in gene expression were noted at day 42 that coincided with cognitive decline.
“Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may provide clues to finding ways that can potentially block neurodegeneration,” co-lead researcher Anthony Pacholko, postdoctoral associate in neuroscience at Weill Cornell Medical College, said.>
