Lecture 2 - The Hypothalamus Neuropeptides and Central Circuits Flashcards
Obesity a ______ of the brain
disease
why is it difficult to lose weight once gained
increased body fat alters brain function
long term obesity induces brain re-programming
CNS influences energy balance and body weight by what 3 mechanisms
behaviour
ANS activity
Neuroendocrine system
Main CNS centre responsible is the
hypothalamus
in the hypothalamus lesion of ________ _________ causes obesity
ventromedial hypothalamus
in the hypothalamus lesion of the ______ ___________ causes leanness
lateral hypothalamus
The energy balance of an individual is controlled by ________ _________
- these act to maintain constancy of total body energy stores
feedback loops
The energy balance of an individual is controlled by feedback loops
- these act to maintain _______ of total body energy stores
constancy
injection of muscimol (GABAa receptor agonist) into VMN, PVN, or DMN stimulates ______
feeding
injection of what into VMN, PVN or DMN stimulates feeding
muscimol
OPIODS
beta endorphin, dynorphin and long-acting enkephalin analogues injected into DMN, VMN, ARC or PVN stimulates _____ feeding and effects are short lived
feeding
MONOAMINES
Noradrenaline, dopamine and serotonin (5-HT) all _____ food intake. Many anti-obesity drugs developed to act on monoamine system and most suffer with what
suppress food intake
most withdraw due to side affects
regulatory peptide molecules can be (neuropeptides)
Orexigenic and Anorexigenic
name a few anorexigenic neuropeptides
leptin, insulin, alpha MSH, GLP1, TRH, CRH, PYY, CART
name a few oreigenic neuropeptides
NPY, MCH, endocannabinoids
NPY is a __ amino acid peptide (number)
36
NPY is one of the _____ ______ peptides in the human brain
most abundant
where are there significant numbers of NPY
ARC and DMN
injection of NPY into hypothalamus potently ______ food intake
stimukates
injection of NPY into hypothalamus potently stimulates food intake, reduces energy expenditure and induces _____ enzymes in fat and liver cells
lipogenic
repeated administration of NPY to hypothalamus leads to
obesity
NPY receptor antagonists or antisera attenuate
feeding and weight gain
NPY gene expression is increased during ______ and decreased after _______
fasting
feeding
NB mice lacking NPY receptor subtypes, Y1, or Y5 are predisposed to mild
obesity
alpha MSH, a non opiod peptide is encoded by what
proopiomelanocortin (POMC) gene
POMC gene expression is reduced on fasting and increased following attainment of
positive energy balance
alphaMSH levels are high in the hypothalamus )Arcuate) and this peptide ______ food intake
inhibts
TWo melanocortin receptor subtypes _____ and ____ are expressed in the brain
MC3 and MC4
depletion of either MC3 or MC4 receptor produces _____ in mice
obesity
agouti-related protein (AgRP)
a mutant mouse displaying ectopic expression of protein is ____
obese
agouti protein induces obesity by antagonising the action of _____ on MC-receptors (MC3 and MC4 rece[ptors in the CNS only
alphaMSH
expression of AgRP is localised to the ARC where it acts as an ______
antagonist
expression of AgRP is localised to the ARC where it acts as an antagonist (actually an inverse agonist) to
MC3 and MC4 receptors
injection (i.c.v) of AgRP causes increased
food intake
injection (i.c.v) of AgRP causes increased food intake - long lasting compared to
NYP
AgRP is co-expressed with NPY in ___ neurons (also contain GABA)
NPY in ARC neurons
Cocaine and amphetamine regulated transcript (CART)
cocaine and amphetamine are _________ and increase CART mRNA
anorexigenic and increase CARTV mRNA
neuropeptide found throughout CNS including hypothalamic centres ARC, VMN, PVN
CART
i.c.v application of CART ____ feeding (short lived) and increases locomotor activity
inhibits
hypothalamic hypoactivity of CART in depression is associated with hyperphagia and
weight gain
CART is co-expressed with
alphaMSH in ARC POMC neurons
second order neurons - PVN peptides
The PVN also regulates _________
pituitary hormone secretion e.g. (thyrotropin releasing hormone)
The PVN also regulates hormone secretion - a good example are Thyrotropin releasing hormone (TRH) neurons that regulate _______ ________ axis
pituitary-thyroid axis
TRH acts as a neurotransmitter/neuromodulator sub-serves various behavioural functions - including ________ and ___-_____
depression and food intake
Corticotropin-releasing hormone (CRH) a 41aa peptide also synthesised in the PVN which controls what
pituitary-adrenocortical system via ACTH secretion
CRH in the PVN elicits numerous actions associated with a state of negative energy
balance
what do magnocellular cells release
release oxytocin and vasopressin `
what does parvocellular release
CRH and TRH
Second Order Neurons
Specific LHA neurons are intensely innervated by ARC projections and these project to numerous other
CNS centres
Second Order Neurons
Two major peptidergic neurons in ___ are important for energy ______
LHA are important for energy homeostasis
Second Order Neurons
Melanin-concentrating hormone - 19aa central injection _____ food intake
increases
Second Order Neurons
mice deficient in MCH eat less, are hyperactive and ____
lean
Second Order Neurons
mice overexpressing MCH are
obese
Orexins (hypocretins) two peptides derived from single precurose ______A and ______B
orexin A and orexin B
central injection of either orexin A or orexin B increases what
food intake
Second Order Neurons
deletion of the orexin gene induces _______ - suggesting ______
narcolepsy
system may be more involved in arousal mechanisms