Abstract Details

Title Gender differences in sleep homeostasis: Pharmacogenetic approach to examine the role of melanin concentrating hormone

Topic Sleep

Presentation(s) N6 - Neuroscience in the Clinic: The Brain Across the Menstrual Cycle (4:35 PM-4:50 PM)

Poster/Presentation
Number 004

Objective

The objective of this research was to understand the neuronal mechanisms responsible for differential homeostatic sleep response in males and females mice.

Background Male and female have minimal differences in spontaneous sleep. However, gender differences have been observed in recovery sleep following sleep deprivation. Recent studies suggest that neurons containing melanin-concentrating hormone (MCH) has a crucial role in sleep regulation. More importantly, the expression of MCH and its receptors is modulated by the female sex hormone, estrogen. Is MCH responsible for differential homeostatic response in males and females mice?

Design/Methods To address this question, we performed pharmacogenetic silencing of MCH neurons in male (N=5) and female (N=10) MCH-cre transgenic mice (expression of cre-recombinase under MCH promoter control). Mice were implanted with sleep recording electrodes. Inhibitory DREADD (AAV/hSyn-DIO-hM4Di-mCherry; 300nl/site) was bilaterally infused in MCH-rich lateral hypothalamus. On experiment day (diestrus or proestrus day in females), sleep deprivation (6 hours)-recovery sleep (3 hours) paradigm was used to examine homeostatic response. Chemogenetic silencing was achieved by systemic administration of clozapine-N-oxide (CNO; 5 mg/Kg/300µL). Control experiment (second sleep deprivation-recovery sleep with 0.9%; 300 µL) was performed in the same mice, three days later, coinciding with diestrus or proestrus day in females. On completion, mice were euthanized, brain removed and processed for MCH immunofluorescence to determine the percentage of MCH neurons with DREADD expression.

Results DREADD was expressed in >50% of MCH neurons. Statistical analysis suggested that as compared to males, pharmacogenetic silencing had differential effects on sleep homeostasis only when females were in proestrus stage. Male and females during diestrus stage had comparable values.

Conclusions Our preliminary results suggest that MCH neurons may have a causal role in differential homeostatic response observed in male and female mice.

Authors/Disclosures
Mahesh M. Thakkar (Department of Neurology) PRESENTER	No disclosure on file
	No disclosure on file
Pradeep K. Sahota, MD, FAAN	The institution of Dr. Sahota has received research support from VA Merit award.

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