The slowdown of the brain with old age is due to the lack of a brain chemical which helps neurons to be selective about what they respond to, reveals research involving the world’s oldest monkeys. Higher brain functions, such as visual recognition or understanding language, require the processing of information in the brain but decline as people get older. This decline appears to be due to a reduction in a neurotransmitter called GABA, say researchers, which means neurons with specific tasks become more easily fired by some other stimulus.
Macaque monkeys, with an age equivalent to 90-years in humans, were not as sharp as their younger counterparts in visual tests despite having perfect eyesight. But when they were given drugs to increase levels of GABA in the brain they improved vastly, say the team. Delivering GABA calms the neurons down and they become more selective, says neuroscientist Audie Leventhal, at the University of Utah School of Medicine, who led the study. “They look the same as they did 20 years ago,” he says.
Importantly, this suggests that mental decline could be easily treated, says Leventhal. “The fact is all the cells are still there and functioning, it’s a transmitter problem – it’s treatable,” he told New Scientist.
Tranquillise and sharpen
The study is the first to show that increasing GABA or its effects can reverse mental decline, says Leventhal. But drugs that boost GABA’s effects, such as benzodiazepines, are normally used to tranquillise brain activity not sharpen it. “It is counterintuitive to say that in order to make Grandpa faster, slow down his brain. Nobody was really thinking about giving tranquillisers to an 85-year-old to perk him up – which is the implication of the study,” he says. But he cautions that the team has done no research in humans and that people should not start taking the drugs themselves.
Peter Tyrer, a community psychiatrist at Imperial College London, thinks the findings are “very interesting and novel”. He adds that doctors have sometimes observed a paradoxical effect of benzodiazepine drugs in which rather than calming down, people had become more alert and aggressive.
The reason GABA is so important in the brain is that it works as a “gating” mechanism, explains Leventhal. By helping neurons to respond only to specific stimuli, it enables the brain to make sense of the vast quantity of incoming information. However, as people get older the neurons in their brains increasingly fire non-selectively. Interpreting information then becomes like listening to “whispering in the discotheque as opposed to shouting in a quiet room,” Leventhal says.
In the work with the young and old monkeys, his team examined neurons in the part of the brain’s vision cortex associated with orientation and shape. He says this is analogous to the region used for vision in humans. The researchers measured the neuronal responses in monkeys watching computer screens displaying various stimuli, such as moving horizontal lines or flashing dots. Certain neurons should only have been activated in response to specific stimuli – but this was not the case in the oldest monkeys.
When GABA and a GABA-enhancing drug were delivered to the brain cells, the team saw an improvement in the selectivity of neurons in the older animals within a couple of minutes.
Leventhal believes a lack of GABA as people age will not just affect vision but all higher brain functions. The team is now exploring the effects of GABA further and has filed patent applications for this new role of GABA-enhancing drugs in humans.