Embedded Files
Exercise Rescues the Cholinergic Forebrain
Exercise Rescues the Cholinergic Forebrain
1. Exercise rescues cholinergic functioning:
1. Exercise rescues cholinergic functioning:
The forebrain cholinergic system is critical for successful memory and learning. It is the brain system that is first affected in several neurodegenerative diseases. However, cholinergic neurons are very responsive to neurotrophin regulation. A timely neurotrophin signal can rescue cholinergic neurons from degeneration. Exercise increases several neurotrophins for a sustained period of time. We found that exercise rescues a selective population of cholinergic neurons, those that co-express nestin. Using a procedure that sequestered BDNF or NGF, we found that NGF—not BDNF-- is the critical neurotrophin responsible for exercise-induced recovery of the cholinergic system.
The forebrain cholinergic system is critical for successful memory and learning. It is the brain system that is first affected in several neurodegenerative diseases. However, cholinergic neurons are very responsive to neurotrophin regulation. A timely neurotrophin signal can rescue cholinergic neurons from degeneration. Exercise increases several neurotrophins for a sustained period of time. We found that exercise rescues a selective population of cholinergic neurons, those that co-express nestin. Using a procedure that sequestered BDNF or NGF, we found that NGF—not BDNF-- is the critical neurotrophin responsible for exercise-induced recovery of the cholinergic system.
2. Measuring and modulation frontocortical acetylcholine release and behavior:
2. Measuring and modulation frontocortical acetylcholine release and behavior:
Modulation of acetylcholine alters attention and memory. Adolescent binge alcohol exposure suppresses about 50% cholinergic neurons in the nucleus basalis that projects to the entire cortical mantle—including the prefrontal cortex. Our recent data demonstrate that if we block the p75NTR cell death pathway we can recover acetylcholine activity in the prefrontal frontal cortex and prefrontal cortical-dependent behaviors, which are dysfunctional after adolescent alcohol binge exposure. We employ multiple methods for measuring molecules: in vivo microdialysis and fiber photometry.
Modulation of acetylcholine alters attention and memory. Adolescent binge alcohol exposure suppresses about 50% cholinergic neurons in the nucleus basalis that projects to the entire cortical mantle—including the prefrontal cortex. Our recent data demonstrate that if we block the p75NTR cell death pathway we can recover acetylcholine activity in the prefrontal frontal cortex and prefrontal cortical-dependent behaviors, which are dysfunctional after adolescent alcohol binge exposure. We employ multiple methods for measuring molecules: in vivo microdialysis and fiber photometry.
Circuits affected by alcohol-related brain damage
Circuits affected by alcohol-related brain damage
3. Alcohol-related brain damage:
3. Alcohol-related brain damage:
We have made several discoveries about what factors contribute to alcohol-related brain damage: (1) Thiamine deficiency, a symptom of malnourishment associated with long-term alcoholism, leads to selective loss of anterior and midline thalamic regions. This in turn leads to circuit dysfunction with the limbic system and the frontocerebellar system, which contributes to the enduring cognitive deficits associated with alcoholism. (2) Exposure to extreme binge-like alcohol drinking during adolescence lead to loss of cholinergic forebrain neuronal populations, and different regions (medial septum/diagonal band vs nucleus basalis magnocellularis) have different sensitivities that lead to the emergence of cognitive dysfunction on different time scales. (3) We are currently examining how the brain rewires as it ages with alcohol-related brain damage.
We have made several discoveries about what factors contribute to alcohol-related brain damage: (1) Thiamine deficiency, a symptom of malnourishment associated with long-term alcoholism, leads to selective loss of anterior and midline thalamic regions. This in turn leads to circuit dysfunction with the limbic system and the frontocerebellar system, which contributes to the enduring cognitive deficits associated with alcoholism. (2) Exposure to extreme binge-like alcohol drinking during adolescence lead to loss of cholinergic forebrain neuronal populations, and different regions (medial septum/diagonal band vs nucleus basalis magnocellularis) have different sensitivities that lead to the emergence of cognitive dysfunction on different time scales. (3) We are currently examining how the brain rewires as it ages with alcohol-related brain damage.
Report abuse