Wee 11 - Hypothalamic control Flashcards

1
Q

where are the hypothalamus and pituitary?

A

diancephalon

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2
Q

hypothalamus control centers

A

It is crucial to the control of feeding, plasma osmolality, body temperature, and sexual and stress responses.
That control always involves negative feedback, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
Some control systems maintain homeostasis — keeping some aspect of the internal environment (e.g. osmolality) roughly constant despite disturbances. Other control systems vary things through time, e.g. in circadian rhythms.

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3
Q

how does the hypothalamus exert its influence neurally and hormonally

A

Nuclei within the hypothalamus send neural signals to each other and to other parts of the brain.
The hypothalamus also synthesizes hormones which it transports
down axons to the posterior lobe of the pituitary, where they are
released into the blood.
And the hypothalamus makes releasing hormones that travel
through capillaries (the hypophyseal portal system) to the anterior
pituitary, where they trigger the release into the blood of other
hormones, made in the pituitary.

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4
Q

when do mice become obese

A

when they have lesions in the ventromedial hypothalamus

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5
Q

what do mice become thin

A

when they have lesions in the lateral hypothalamus

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6
Q

what are the ventromedial and lateral hypothalamus controlled by?

A

two groups of neurons in the arcuate nucleus of the hypothalamus: arcuate NPY cells drive feeding while arcuate POMC inhibit feeding

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7
Q

what happens in the fasting state

A

arcuate NPY neurons encourage feeding.
They release neuropeptide Y (NPY), GABA, and in some cases also agouti-related peptide (AgRP)

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8
Q

what does Arc NPY inhibit

A

Signals from Arc NPY cells inhibit neurons in the periventricular nucleus, a satiety or anorexigenic center that quells appetite for food.
PVN usually excites the sympathetic nervous system, but Arc NPY acts via PVN to decrease sympathetic activity.
High sympathetic activity usually inhibits feeding, but because Arc NPY inhibits sympathetic activity, it disinhibits feeding behavior.

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9
Q

what does Arc-NPY excite

A

it excites neurons in the lateral hypothalamus, a feeding centre. Projections from LH release orexin at their synapses, inhibiting PVN and stimulating feeding behaviour.

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10
Q

what happens in the postprandial state?

A

arcuate POMC neurons inhibit feeding. they are a group of neurons in the arcuate neurons containing pro-opiomelanocortin.
they cleave POMC to make alpha-melanocyte stimulating hormone which they release at their synapses.

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11
Q

what does alpha-melanocyte stimulating hormone excite

A

neurons in the PVN and the ventromedial nucleus.
this excites the sympathetic nervous system.

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12
Q

what does alpha melanocyte stimulating hormone inhibit

A

neurons in the dorsomedial hypothalamus.
Activity in DMH usually inhibits the sympathetic nervous system, but Arc POMC inhibits DMH, so the net result is that sympathetic activity is disinhibited (increased)

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13
Q

what does combined excitation and inhibition by alpha melaocyte stimulating hormone cause

A

stron inhibition of feeding

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14
Q

what is Arc POMC excited and inhibited by

A

excited by the sympathetic nervous system (+ve feedback loop) and inhibited by Arc NPY

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15
Q

how does control of feeding work

A

works based on negative feedback, on signals that tell the control center how close the system is to some goal state, or set point

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16
Q

set points in rats with lesions

A

rates with VMH lesions dont get fatter and fatter forever, but level off at a new set point above their original weight and rats with LH lesions level off at a new low-set point.

17
Q

how does hypothalamus infer body weight

A

leptin levels

18
Q

leptin

A

protein released into the blood mainly by fat cells, so the more fat you have, the more circulating leptin

19
Q

leptin receptors

A

some cells in the body have membrane receptors for leptin, including cells in the feeding and anorexigenic centers of the hypothalamus.

20
Q

what causes obesity

A

mutations in the genes that produce leptin or the leptin receptor cause obesity in mice and humans

21
Q

what does leptin inhibit and excite - Arrc-NPY

A

leptin inhibits feeding centers Arc-NPY and LH and excites PVN which boosts sympathetic activity inhibiting feeding

22
Q

what does leptin inhibit and excite - Arc-POMC

A

it inhibits DMH and excites Arc POMC and VMH (boosting sympathetic activity)

23
Q

how does brain known when to end a meal

A

not from leptin - beacuase it is too slow
through blood glucose; it increases as you eat, and its rising level excites Arc POMC and inhibits LH, inhibiting further feeding
other mechanisms involve sensors in the wall of the stomach and intestines that measure nutrients and stretch, and response by releasing hormones that act on the hypothalamus

24
Q

postprandial state - gut hormones

A

inhibit feeding
sensors in the wall of the small intestine detect stretch, sugar and protein, leading to the release of cholecystokinin (CCK), peptide YY, and glucagon like petide 1\

25
Q

in fasting what is released from the stomach

A

ghrelin released from the stomach encourages feeding
it is released into the blood by cells in the stomach wall when the stomach is empty stretching the stomach stops ghrelin release

26
Q

what does ghrelin act on

A

it acts directly on Arc-NPY and LH (exciting them) and on PVN (inhibiting it)

27
Q

rimonabant

A

blocks CB1 endocannabinoid receptors, can lead to moderate weight loss, but causes depression, major weight loss and suicide

28
Q

amphetamines and fenfluramine

A

an anti obesity drug withdrawn in 1997 because of cardiovascular side effects

29
Q

leptin as a drug

A

rarely helps, because fewer than 1% pf humans with morbid obesity are leptin-deficient.

30
Q

CCK and PPY agonists

A

not much success

31
Q

liraglutide

A

GLP1 agonist, works better