Feeding patterns and adult hippocampal neurogenesis: ghrelin

Question 1

what is adult hippocampal neurogenesis

Answer 1

ongoing process of generating functionally integrated neurons from progenitor cells under adult brain conditions - aka birth of new adult born nerve cells

affects brain structure and plasticity

Question 2

how long does adult hippocampal neurogenesis take

Answer 2

approx 7 weeks

Question 3

where does adult hippocampal neurogenesis take place - 2

Answer 3

subventricular zone of lateral ventricles

dentate gyrus of hippocampus

Question 4

what is the subgranular zone

Answer 4

niche in dentate gyrus where neurogenesis pools - multipotent stem cells

Question 5

what are the stem cell types that are found in the subgranular zone of dentate gyrus

Answer 5

type 1 - radial glial like, express proteins like nestin

type 2 - typically express SOX2

type 3 - more differential, neuronal role

Question 6

how many types of stem cells are found in the subgranular zone of dentate gyrus

Answer 6

3

Question 7

what is adult hippocampal neurogenesis necessary for

Answer 7

pattern separation memory - ability to distinguish between very similar contexts

difficult in pstd

Question 8

what does adult hippocampal neurogenesis decline with - 4

Answer 8

age
stress
depression
dementia

Question 9

what does adult hippocampal neurogenesis increase with - 4

Answer 9

exercise
environmental enrichment
antidepressants
diet-calorie restriction

Question 10

is calorie restriction effect conserved across species

Answer 10

yes, conserved nutrient signalling pathways AMPK (lead to inc cell metabolism and insulin sensitivity)

Question 11

calorie restriction has been associated with

Answer 11

improvements in learning and memory

mechanisms are less known - thought to mediate via promoting hippocampal plasticity and neurogenesis, potentially though ghrelin (mice studies)

Question 12

ghrelin and calorie restriction

Answer 12

circulating ghrelin inc during calorie restriction, positively modulates learning and memory processes

unique as all other GI hormones reduced during calorie restriction

Question 13

ghrelin has how many amino acids

Answer 13

28

Question 14

what type of peptide is ghrelin

Answer 14

orexigenic peptide (promotes eating)

Question 15

what is ghrelin produced by

Answer 15

PD/1 cells in stomach

Question 16

ghrelin function

Answer 16

regulates GH release from pituitary

hunger hormone

Question 17

what are the two forms of ghrelin

Answer 17

acyl ghrelin AG - active form

unacylated ghrelin UAG

Question 18

ghrelin on 3rd serine residue is

Answer 18

octanoylated (occurs in acylation)

octanoic acid comes from coconut, dairy intake in diet

Question 19

what enzyme performs acylation/ activation in stomach

Answer 19

GOAT, ghrelin O - acyl transferase

Question 20

ghrelin functions through what receptor

Answer 20

GHSR1a , a GPCR

Question 21

GHSR-eGFP - transgenic mouse model ghrelin results - where is ghrelin expressed/ not expressed

Answer 21

ghrelin not expressed on type 1 or type 2 (NSPCs), or proliferating cells (Ki67+)

widely expressed in granular cell layer of dentate gyrus on mature granule cells (NeuN+)

Question 22

what are NSPCs

Answer 22

neural stem and progenitor cells

Question 23

what is Ki67+

Answer 23

marker for cell proliferation

Question 24

what is NeuN+

Answer 24

marker for mature neuronal cell

Question 25

does acyl-ghrelin enhance AHN - rat results

Answer 25

in rats, AG treatment sig inc AHN in dentate gyrus, improved memory in pattern separation memory task no sig effect on rate of stem cell self renewal or new astrocyte formation across rostro-caudal axis of dentate gyrus so overall good as inc memory, no neg impact to other stuff

Question 26

what is BrdU

Answer 26

thymidine analogue

Question 27

does calorie restriction have neurogenic effect on brain like acyl ghrelin does? rat results study

Answer 27

in rats, no change in terms of c-Fos expression/ neuronal activity but Egr-1 expression/ integration of newborn neuronal cell increases both in calorie restriction and ghrelin

Question 28

what is c-Fos

Answer 28

protoncogene, marker for neuronal activity

Question 29

what is Egr-1 role

Answer 29

promoting functional integration of newborn cells into dentate gyrus

Question 30

does calorie enhance AHN via GHSR / ghrelin receptor signalling rat results study

Answer 30

GHSR knockout mice - calorie restriction in 2 weeks, then behaviour task, and tissues collected inc neurogenesis by 52% in GHSR-dependent manner

Question 31

effect of unacylated ghrelin on AHN rat results

Answer 31

GOAT knockouts - no AG and lots of UAG - 40% reduction in proliferating cells in knockout and WT with extra UAG reduction in immature neurons (shown via DCX+ - immature neuronal marker) reduction in newborn cells and non-neuronal cells overall, dec in neuronal plasticity behaviour wise, dec in spatial memory (maze task)

Question 32

how much of circulating ghrelin is unacylated

Answer 32

approx 85%

Question 33

can AG injections rescue a prev lack thereof

Answer 33

single injection - no 7 days AG treatment - memory deficits rescued

Question 34

can ghrelin be used as a biomarker of cog decline - pilot study results

Answer 34

PD dementia and mild cog decline pts bloods collected showed PD mfs have altered post-prandial (after munch) ghrelin response and altered AG lvl compared to controls AG as a % of total ghrelin dec in fasting and post prandial PD pts

Question 35

post-prandial

Answer 35

after meal

Question 36

effects of other feeding patterns - not restrictive eating rat results

Answer 36

in mice with ghrelin knockouts, 3 weeks: free access to food vs grazing animals (eat little, often) vs 3 feedings a day spatial memory task 3x a day: inc neuronal mature cells produced if no ghrelin receptor, meal feeding effect lost (aka less spatial memory and learning) anxiety behaviour = open field test . meal fed were less anxious, absence of ghrelin receptor reversed anti anxiety effect of meal feeding

Question 37

what is ab libitum

Answer 37

as much or as often as necessary or desired

Question 38

calorie restriction and ghrelin promote

Answer 38

AHN

Question 39

AHN is mediated by

Answer 39

GHSR

Question 40

GHSR is highly expressed in

Answer 40

mature DG neurons also expressed in basolateral amygdala (fear) and lateral entorhinal cortex (alzheimers)