Schulz 2013 - Effects of PS on α4β2 and α7 Hippocampal nAChR Levels in Adult Offspring

Prenatal Stress (PS)

Stress experienced by a mother during pregnancy that may affect the development of her offspring.

Nicotinic Acetylcholine Receptors (nAChRs)

Receptors in the brain that respond to the neurotransmitter acetylcholine and are implicated in various psychiatric disorders.

Alpha4-Beta2 (α4β2*) nAChR

A subtype of nicotinic receptor implicated in nicotine addiction, learning, and cognitive function.

Alpha7 (α7*) nAChR

A subtype of nicotinic receptor involved in learning and memory and MIs like depression and anxiety. Can influence neuroinflammation.

Cholinergic Dysfunction

Impairments in acetylcholine signaling that may contribute to psychiatric conditions.

Quantitative Autoradiography

A technique used to measure the binding of specific ligands to receptors in brain tissue.

Molecular Layer of Dentate Gyrus (MoDG)

• receives excitatory inputs from the entorhinal cortex

• Influences the activity of dentate granule cells

• Contributes to pattern separation and memory encoding

Polymorphic Layer of Dentate Gyrus (PoDG)

• Communication between the dentate gyrus and CA3

• Contains mossy cells, which project to the CA3 region, and GABAergic interneurons, which provide inhibitory connections.

Alveus

• Part of the fornix in the hippocampus

• important role in the process of learning

• formation of new memories

• the reproductive cycle

Lacunosum moleculare of CA1 (LMol CA1)

• Relay between the entorhinal cortex (EC) and CA1

• Strength and timing of hippocampal activity

Lacunosum moleculare of CA3 (LMol CA3)

• Connects the entorhinal cortex (EC) with CA1

• influences CA1's activity during different behavioral states.

What causes the axiolytic affects associated with smoking nicotine?

Decreased cholinergic signaling in the brain (drug).

What effects do acetylcholinesterase inhibitors have on humans?

Decreased depression and anxiety symptoms

What were the number of subjects and the groups in this study?

37 Sprague-Dawley rats, either in no stress or prenatal stress groups.

Describe the prenatal stress protocol

• Unpredictable variable stress 2–3 times daily between 9 a.m. and 5 p.m. during gestational days 14–21

  • restraint in cylindrical restrainers (30 min)

  • exposure to a cold room at 4 °C (6 h)

  • swim in water at room temperature (15 min)

  • social stress - 5 rats/cage (9 h)

  • overnight fast

  • exposure to loud radio static (80 db, 60 min)

  • transport on a noisy cart (30 min)

At what age were brains collected?

• PD 56 (early adulthood)

What was used to measure α4β2 binding?

Epibatidine.

What was used to measure α7 binding?

α-bungarotoxin (a-BTX)

What was used to define nonspecific binding?

Nicotine

What were the three things analyzed for an effect on binding?

1. Sex

2. Hemisphere

3. Stress condition

What were the sex specific findings for α7 nAChR (3 things)?

Females

1. LMol CA1: PS eliminated normal left-biased lateralization

2. MoDG & PoDG: Trends toward PS-induced increase

Males

3. No effect of PS or hemisphere on α7* binding

Describe the α7 nAChR lateralization.

In females, PS eliminated normal left-biased lateralization in the LMol CA1, with a trend towards a PS-induced increase in the MoDG & PoDG.

In both sexes, there was a left-biased lateralization of α7 nAChR in all other layers of the CA1.

Describe the α4β2 findings.

PS increased α4β2 binding in the LMol CA1, LMol CA3, and MoDG. So, every area but the PoDG.

What receptor type is most influenced by sex?

α7 nAChR

What brain region is most influenced by sex?

LMol CA1

What does the finding that PS increases α4β2* nAChRs in the hippocampus of both sexes mean?

This possibly contributes to increased cholinergic activity which is linked to depression and anxiety. Non-sex-specific symptoms of these MIs.

What does the finding that there is disruption of normal lateralization of α7* receptors in females mean?

This may relate to altered hippocampal function and psychiatric vulnerability seen in females.

What is the importance of the lateralization findings to humans?

Schizophrenia and other MIs are characterized by atypical or absent lateralization in the hippocampal cholinergic system