Pineal gland, blood-brain barrier

Question 1

Cell types of Pineal gland

Answer 1

1. Pinealocytes (modified neurons)
2. Astrocytes/glial cells (provides structural and metabolic support)

Question 2

Hormone produced by pineal gland

Answer 2

Melatonin

Question 3

Function of melatonin from pineal gland

Answer 3

Maintenance of circadian rhythm

Question 4

What causes the brain to trigger pineal gland?

Answer 4

• Use both circadian (daytime vs. nighttime) and circannual rhythm
• Light during the day, less melatonin released by pineal gland
• Darkness= more melatonin

Question 5

Pituicytes (astrocytes, glial cells)

Answer 5

• Cells within the pituitary gland
• Supportive cells

Question 6

Circadian and Circannual regulation in horse

Answer 6

Use both circadian rhythm (daily light and dark) and circannual rhythm (tidal, lunar, annual) to regulate body systems/functions
- However, melatonin is not well understood in horses and may not have a main role in the cycle in horses

Ex. circadian rhythm- activity level, body temp

Ex. circannual- reproduction, hair coat, growth, mood

Question 7

Circadian Trends in Prolactin and Melatonin Secretion in Murrah Buffalo Heifers

Answer 7

Circadian pattern that influences the release of prolactin and melatonin. More released during nighttime for melatonin. Slight increase later in day for prolactin but not throughout the night

Question 8

Circadian GH secretory profiles in Dogs

Answer 8

• Growth hormone release was slightly higher in the day than at night, but there was no significant different between the release time of day
• Study shows individual variation of release between individuals

Question 9

Circannual/seasonal changes in growth hormone secretion in male dogs

Answer 9

• Release much lower during the spring compared to the other seasons
• Release highest in the summer, but similar to autumn and winter

Question 10

Pulsatile Secretion of growth hormone

Answer 10

There can be variation in hormone release throughout the day. Hormones show pulsatility (peaks and troughs)

Strenuous exercise and first few hours of sleep causes increase in growth hormone release

Question 11

Negative feedback of hormone release

Answer 11

• Too much hormone release will most likely result in negative feedback since too much hormone can prevent proper function.
• Can play a role in pulsatility of hormone release

Question 12

Half-life of hormones in circulation

Answer 12

• Hormones have a half-life once released and circulated in body
• Defined as the amount of time required for half of the molecules to become inactivated or cleared from circulation

Question 13

Peptide hormones and half-life

Answer 13

• Short half-life = 2-30 mins
• Proteolytic enzymes will inactivate/convert peptide to other forms upon secretion
  -Site of inactivation is cell
  membrane itself or in
  tissue fluids

Question 14

Thyroid stimulating hormone (TSH) half life

Answer 14

Half-life of 60mins

Question 15

Hormone inactivating enzymes

Answer 15

Exopeptidases

Endopeptidases

Question 16

Exopeptidases

Answer 16

Act on C- and N- terminal of peptides and break them down/inactivate them

Eg. Carboxypeptidase/aminopeptidase

Question 17

Endopeptidases

Answer 17

Cleaves peptides at specific sites within the peptide

Eg. Insulinase- Acts on insulin

Eg. dipeptidyl peptidase family. Acts on a number of target peptide hormones including glucagon like peptide-1 (GLP-1)

Question 18

Ways to increase half-life

Answer 18

Amidation or other post-transitional modifications

• Can help bioactivity and increase half-life
• Can be used in drug design and delivery

Question 19

Blood-Brain Barrier

Answer 19

• A continuous endothelium of capillaries with tight junctions, basal membrane, astrocytes, pericytes (multi-functional, contractile cells), and neurons
• Forms a selectively permeable barrier that restricts movement of ions and molecules, including hormones, between the brain and the blood

Question 20

Cells of the blood brain barrier

Answer 20

• Pericyte
• Endothelial cell
• Neuron
• astrocyte

Question 21

Functional implications of the Blood-brain barrier and considerations in veterinary medicine

Answer 21

Certain hormones can’t reach the brain, and certain hormones from the brain can’t reach the periphery
- Affects functions of the hormones because there is no longer free access to receptors in the brain

In medicine, before making a decision need to look at whether the drug can pass the blood-brain barrier and at its half-life

Question 22

Blood-brain barrier dysfunction

Answer 22

• likely plays a role in epileptic seizures
• Study found that 37% of dogs that had seizures also had BBB dysfunction

Question 23

P-Glycoprotein in the BBB & role in multidrug resistance

Answer 23

In neural capillary (brain): no fenestra and intercellular clefts for movement. Instead has P-glycoproteins that function as pumps that will pump out drugs that come in from periphery and prevent neurotoxicity. Therefore P-glycoproteins allow for drug resistance
o Ex. Ivermectin- Has P-glycoproteins (MDR1) pump out drug and prevent it from getting to the brain. Some breeding dogs do not have these P-glycoproteins and drugs are not pumped out of brain.

Question 24

Movement into non-neural capillary

Answer 24

Fenestra and intercellular clefts within endothelial cells allow access of materials throughout the endothelium