As part of a global research effort, scientists have discovered a relationship between metabolism problems in the brain and a range of neuropsychiatric and neurodegenerative disorders, from autism to Alzheimer’s disease and more .
Despite their diverse symptoms, these conditions – as well as depression, epilepsy, schizophrenia, intellectual disability and bipolar disorder – all involve some degree of cognitive impairment and often share genetic or metabolic characteristics, hinting at a biological basis. common.
The broad collaboration of the International Brain pH Project Consortium, involving 131 scientists from 105 laboratories in seven countries, identified changes in brain acidity and lactate levels in animals as key signs of this metabolic dysfunction.
“We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism,” the team writes in their published paper.
“However, research on this phenomenon in animal models is still limited, leaving its generality in other pathological animal models uncertain.”
Their findings could lead to new ways of diagnosing and treating these complex disorders that affect a large part of the world’s population.
“This research could provide a stepping stone toward identifying common therapeutic targets in various neuropsychiatric disorders,” says molecular and cellular physiologist Masayuki Matsushita of the University of the Ryukyus in Japan.
Changes in lactate can impact information transfer in neurons by disrupting the functional balance between excitatory and inhibitory brain networks. Increased lactate levels in the brain can lead to lower pH, which evidence suggests is another common feature of most of the disorders studied here.
By examining whole brain samples from several animal models, including mice, rats and chicks, some genetically modified to mimic different neuropsychiatric and neurodegenerative diseases, the team discovered consistent changes in brain pH and lactate levels. .
“This is the first and largest systematic study evaluating brain pH and lactate levels across a range of animal models for neuropsychiatric and neurodegenerative disorders,” says first author Hideo Hagihara, a medical scientist at the Fujita Health University in Japan.
Remarkably, about 30 percent of 2,294 The animals studied, in 109 different models, showed significant changes in pH and lactate levels. This implies that these disturbances are common in many neuropsychiatric pathologies.
Animal models representing stress-induced depression, diabetes or colitis – all of which lead to a higher risk of depression – have shown a consistent trend toward decreased brain pH and increased lactate levels.
This suggests that various genetic or environmental factors that may induce these differences, such as inflammation, could influence brain metabolism and contribute to the development of neuropsychiatric disorders.
Various responses were observed in autism models, with some showing increased pH and decreased lactate levels, while others showed an opposite trend. This suggests that there may be various subgroups of metabolic dysfunctions in people with autism spectrum disorders.
And in behavioral testing, the team noted a strong link between high lactate levels and impaired working memory performance, which they say shows that metabolic dysfunctions can have a direct impact on abilities. cognitive disorders in various neuropsychiatric disorders.
Mitochondrial dysfunction is linked to several neuropsychiatric disorders that often present with working memory deficits as a common symptom. Mitochondrial dysfunction in neurons can result in decreased lactate consumption for energy production, with its accumulation potentially leading to impaired learning and memory functions.
But lactate production is also necessary for memory formation, so decreased levels could also contribute to dysfunction.
Overall, the authors say their results indicate that changes in brain pH and lactate levels, although these changes contribute to a benefit, can serve as biological markers for neuropsychiatric disorders associated with cognitive impairment.
“Future studies will focus on discovering effective treatment strategies in various animal models with changes in brain pH,” says Miyakawa.
“This could significantly contribute to the development of tailored treatments for subgroups of patients characterized by specific alterations in brain energy metabolism.”
The research was published in eLife.
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