Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus

Nicholas J Hunt1, Michael L Rodriguez2, Karen A Waters3

  • 1Department of Medicine, Central Clinical School, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, BOSCH Institute of Biomedical Research, University of Sydney, New South Wales, Australia.

Neurobiology of Aging
|September 13, 2014
PubMed

Insights

Orexin (Ox) expression decreases with human aging and development. This reduction in the tuberal hypothalamus may impact sleep regulation throughout life.

Area of Science:

  • Neuroscience
  • Aging Research
  • Sleep Science

Background:

  • Animal studies suggest orexin (Ox) expression changes impact sleep regulation during aging.
  • Orexin, a neuropeptide, plays a crucial role in maintaining wakefulness and regulating sleep-wake cycles.

Purpose of the Study:

  • To investigate changes in orexin A and B expression in the human tuberal hypothalamus across different age groups.
  • To determine if orexin expression declines with normal human maturation and aging.

Main Methods:

  • Examined orexin-immunoreactive (Ox-ir) neurons in the tuberal hypothalamus of infants, children, young adults, and older adults.
  • Quantified neuronal expression by percentage of Ox-ir neurons, neuron density (Ox-ir neurons/mm²), and regional distribution within the hypothalamus.

Main Results:

  • A significant decrease in the percentage of Ox-ir neurons was observed between infants and older adults (23%) and between younger and older adults (10%).
  • These age-related decreases in orexin expression were localized to the dorsal medial and/or perifornical hypothalamus.
  • Adults showed a 9%-24% reduction in Ox-ir neurons/mm² compared to infants and/or children.

Conclusions:

  • Orexin expression significantly decreases with normal human maturation and aging.
  • Reduced orexin levels may contribute to age-associated alterations in sleep regulation.
  • These findings highlight the role of orexin in developmental and aging-related changes in sleep patterns.

Related Concept Videos

Sleep-Wake Cycles01:24

Sleep-Wake Cycles

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
2.9K
Diencephalon: Hypothalamus and Coordination01:23

Diencephalon: Hypothalamus and Coordination

The hypothalamus is a small yet highly complex and essential brain region that plays a crucial role in regulating various bodily functions. Anatomically, it is located at the base of the brain, just above the brainstem and below the thalamus, forming part of the limbic system.
The hypothalamus interacts with other brain regions, including the pituitary gland, through a direct physical connection called the hypothalamic-pituitary axis. The hypothalamus receives somatic and visceral inputs and...
4.5K
Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
2.8K
Aging01:26

Aging

Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
1.1K
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
3.4K
Diencephalon: Anatomical Regions01:30

Diencephalon: Anatomical Regions

The diencephalon, etymologically translated as 'through brain,' plays an integral role as the conduit between the cerebrum and the vast extent of the nervous system. However, the olfactory system is an exception, as it interfaces directly with the cerebrum. The diencephalon, deeply ensconced beneath the cerebrum, primarily consists of three paired structures — the thalamus, hypothalamus, and epithelamus. It also includes accessory structures such as the subthalamus, which houses the...
5.9K