Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment
We previously published about this research in a story titled “Scientists have Discovered a Connection Between Metabolic Problems in the Brain and Neurological Disorders” which can be found here. The study was originally published in the research journal eLife. You can read the full text of the study here.
This research was affiliated with the International Brain pH Project Consortium.
What Happened?
Alzheimer’s, autism, schizophrenia, bipolar disorder, depression, and a wide range of other neurological disorders are all associated with some semblance of cognitive impairment and, despite significant variations in presentation, appear to share some metabolic or genetic characteristics. This suggests that these illnesses all share some degree of biological origin.
This study sought to understand the biological similarities that are shared by this vast range of conditions, all of which impact the brain in some way. The study was a massive collaborative effort involving seven countries, 131 researchers, and 105 different laboratories.
The research team looked at whole brain samples from multiple animal models, including rats, chicks, and mice. Many were genetically modified to imitate different neurological disorders. The researchers noted consistent changes in lactate and pH levels in the samples. A total of 2,294 animals were studied for a total of 109 models. Around 30% of those studies displayed changed to lactate and pH.
The findings suggest that changes in these areas were consistently associated with disease, though precisely how they changed depended on the condition. For example, in models intended to represent depression, brain pH decreased while lactate levels increased. Meanwhile, in autism models, a wider range of changes was documented.
Behavioral tests demonstrated a connection between high lactate levels and impairment in working memory. High lactate levels may be related to mitochondrial dysfunction, which has been widely linked to neuropsychiatric disease. Mitochondria normally consume lactate as part of energy generation, so dysfunction could lead to the increase in lactate levels. The authors concluded that changes in lactate levels and brain pH may be reliable biomarkers for diseases that result in cognitive impairment.
Why Does it Matter?
Disorders affecting the brain and neurological system can be challenging to treat. The blood-brain barrier limits the use of medication. Accessibility to effective treatment ranges widely between conditions, with some having multiple effective options and others having none.
The results of this study reveal both a biomarker and also a potential therapeutic target that could help stabilize patients experiencing a diverse array of neurological disease and mental health disorders:
“This could significantly contribute to developing tailored treatments for patient subgroups characterized by specific alterations in brain energy metabolism.” – Tsuyoshi Miyakawa, professor, Fujita Health University, corresponding author
Future avenues of research will focus on revealing therapy strategies that appear effective in animal disease models characterized by changes to brain pH and lactate levels.
“This research could be a stepping stone towards identifying shared therapeutic targets in various neuropsychiatric disorders.” – Masayuki Matsushita, molecular and cellular physiologist, University of the Ryukyus
