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ACTH modulation of nerve development and regeneration.
F L Strand1, K J Rose, J A King
1Department of Biology, New York University, N.Y. 1003.
Progress in Neurobiology
|January 1, 1989
Summary
Adrenocorticotropic hormone (ACTH) peptides, like alpha-MSH, influence neuromuscular and central nervous system development. Early exposure can accelerate maturation, but effects are age-dependent and can lead to long-term behavioral changes.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Adrenocorticotropic hormone (ACTH) 1-39 has known corticotropic and neurotrophic effects.
- Specific peptide fragments, including ACTH 4-10, ACTH 4-9 analog (Org 2766), and alpha-MSH (ACTH 1-13), exhibit neurotrophic properties without stimulating corticosteroid secretion.
- These fragments are crucial for peripheral nerve development and regeneration.
Purpose of the Study:
- To investigate the impact of specific ACTH peptide fragments on the maturation of the neuromuscular system and central nervous system (CNS) in developing rats.
- To determine the age-dependency of these effects during prenatal and postnatal development.
- To explore the long-term behavioral consequences of perinatal ACTH peptide exposure.
Main Methods:
- Administration of ACTH 4-10, Org 2766, or alpha-MSH during specific prenatal and postnatal periods in rats.
- Assessment of neuromuscular development, including muscle contractile strength, motor activity, and grasping strength.
- Histological examination of neuromuscular junction morphology, including nerve arborization and terminal branching.
- Observation of CNS developmental milestones such as eye opening.
- Behavioral testing in adult rats, including motor activity, arousal, social behavior, and sexual behavior.
Main Results:
- Early postnatal administration of ACTH peptides accelerated neuromuscular maturation, enhancing muscle strength and motor activity.
- Prenatal treatment showed complex effects: early gestation administration accelerated development, while later administration decelerated it.
- ACTH peptides increased nerve arborization and terminal branching at the neuromuscular junction, though an initial depression was observed.
- Perinatal exposure accelerated eye opening and induced lasting behavioral changes in adulthood, including altered motor activity, arousal, and social interactions.
- Neonatal alpha-MSH improved certain cognitive functions in males but decreased male sexual behavior and eliminated sexually dimorphic behaviors.
Conclusions:
- The developing neuromuscular and CNS are sensitive to ACTH peptides, with effects being critically age-dependent.
- Optimal therapeutic or developmental effects may be confined to brief, specific developmental windows.
- Perinatal ACTH peptide exposure can significantly and permanently alter neurodevelopmental trajectories and adult behavior, potentially by modulating neurotransmitter systems like dopamine and serotonin.