Which neurons disappear in the brain when estrogen declines during menopause?

Dopamine Neurons Disappear in the Brain When Estrogen Declines During Menopause

The answer is A. Dopamine neurons are the ones that significantly disappear in a major area of the brain when estrogen levels decline during menopause. 1

Neurobiological Effects of Estrogen Decline

Estrogen has profound effects on the brain, particularly on neurotransmitter systems. When estrogen levels decline during menopause, several important changes occur:

Impact on Dopamine System

• Estrogen decline leads to decreased dopamine neurotransmission in key brain regions
• The BMJ (2023) reports that dopamine neurotransmission is critically involved in episodic memory encoding and retrieval via nerve cell signaling 1
• Catechol-O-methyltransferase (COMT), which metabolizes dopamine, has been identified as a risk factor for cognitive impairment when estrogen levels drop 1

Mechanisms of Neuronal Loss

When estrogen levels fall during menopause, several pathways are affected:

1. Reduced neuroprotection:

   • Estrogen normally provides antioxidant effects that protect neurons from reactive oxygen species (ROS) damage 1
   • Without estrogen, dopaminergic neurons are particularly vulnerable to oxidative stress

2. Decreased neuroplasticity:

   • Estradiol normally stimulates dendritic spine production and enhances neuroplasticity 1
   • This occurs via brain-derived neurotrophic factor (BDNF) related mechanisms
   • When estrogen declines, this support is lost, particularly affecting dopamine neurons

3. Altered N-methyl-D-aspartate (NMDA) receptor function:

   • Estrogen decline reduces NMDA receptor concentrations 1
   • This particularly affects dopaminergic pathways in the brain

Clinical Manifestations

The loss of dopamine neurons due to estrogen decline manifests in several ways:

• Cognitive changes: Particularly affecting verbal memory and processing speed 1
• Mood alterations: Dopamine plays a key role in mood regulation
• Changes in reward processing: Dopamine is central to the brain's reward system

Why Other Neurotransmitter Systems Are Less Affected

While other neurotransmitter systems are also influenced by estrogen, the evidence points most strongly to dopamine neurons being particularly vulnerable to disappearance when estrogen declines:

• Serotonin: While serotonin function is modulated by estrogen 2, there is less evidence for widespread serotonergic neuron loss compared to dopaminergic neurons
• Epinephrine: Less directly affected by estrogen decline in terms of neuronal loss
• Cortisol: Represents a hormone rather than a primary neurotransmitter system, and its production is regulated differently

Clinical Implications

Understanding the loss of dopamine neurons during estrogen decline has important implications:

• It helps explain cognitive changes during menopause, particularly verbal memory deficits 1
• It provides a neurobiological basis for mood changes during menopause
• It suggests potential therapeutic targets for managing menopausal cognitive symptoms

The significant impact of estrogen decline on dopamine neurons underscores the complex relationship between hormonal changes and brain function during menopause.