Fasting, mother separation and brain hormones

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Hi All,

Does our maternal closeness affect the effect of fasting/CR on our response to

addictive drugs?

When factors were examined in the below, 60 days after birth, represents fairly

old

young rats.

For definition, there is:

opiomelanocortin: A linear polypeptide of the pituitary gland that contains in

its

sequence the sequences of endorphins, MSH, ACTH, and the like, which are split

off

enzymically; the nucleotide sequences coding has been determined for several

species.

endorphins: One of the three major groups of endogenous opioid peptides. They

are

large peptides derived from the pro-opiomelanocortin precursor.

msh: Peptide hormones secreted by the intermediate lobe of the pituitary that

stimulate melanin release and dispersal. Melanocyte-stimulating hormones are

also

found in the brain where they are presumed to play a signaling role.

ACTH --> adrenocorticotrophic hormone: A peptide hormone that is produced by the

anterior pituitary gland. It stimulates the adrenal cortex to secrete

glucocorticoid

hormones, which help cells synthesise glucose, catabolize proteins, mobilizefree

fatty acids and inhibit inflammation in allergic responses.

?arcuate fasciculus --> superior longitudinal fasciculus: Long association fibre

bundle lateral to the centrum ovale of the cerebral hemisphere, connecting the

frontal, occipital, and temporal lobes; the fibres pass from the frontal lobe

through the operculum to the posterior end of the lateral sulcus where many

fibres

radiate into the occipital lobe and others turn downward and forward around the

putamen and pass to anterior portions of the temporal lobe.

Also, the role of neuropeptide Y (NPY) is explained in the introduction, below.

See

the HTML-only-available paper below.

Kim HJ, Lee JH, Choi SH, Lee YS, Jahng JW.

Fasting-induced increases of arcuate NPY mRNA and plasma corticosterone are

blunted

in the rat experienced neonatal maternal separation.

Neuropeptides. 2005 Oct 30; [Epub ahead of print]

PMID: 16266747

.... Pups in maternal separation (MS) groups were separated from their dam for 3h

daily from postnatal day (PND) 1-14, while pups in non-handled (NH) groups were

left

undisturbed. Rats were sacrificed on PND 60 to examine the gene expression of

neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the hypothalamic arcuate

nucleus by mRNA in situ hybridization. Half of the rats from each group were

food-deprived for 48h before sacrifice. POMC mRNA expression increased in the

free

fed MS group compared with the free fed NH group. Food deprivation significantly

decreased the arcuate POMC mRNA level in both groups. Body weight gain, basal

levels

of plasma corticosterone, leptin, and arcuate NPY mRNA were not modulated by

experience of neonatal maternal separation. However, fasting-induced increases

of

plasma corticosterone and arcuate NPY expression were blunted in MS rats. These

results suggest that neonatal maternal separation may increase the basal

expression

level of arcuate POMC mRNA, while inhibit the fasting-induced expression of

arcuate

NPY mRNA, later in life. Lastly, the altered expression of arcuate NPY mRNA, but

not

of arcuate POMC mRNA, appeared to be related with altered activity of the

hypothalamic-pituitary-adrenal gland axis in offspring by neonatal maternal

separation.

.... experiences of repeated maternal separation during pre-weaning period

increase

the hypothalamic level of neuropeptide Y (NPY) in rats later in life

(Jimenez-Vasquez et al., 2001 and Husum and Mathe, 2002). NPY, the most potent

orexic peptide known, stimulates feeding (Stanley and Leibowitz, 1985, Kalra et

al.,

1999 and Schwartz et al., 2000), and it has been suggested that hypothalamic NPY

expression is regulated, at least partly, by glucocorticoid, which is stress

hormone

released by activation of the hypothalamic-pituitary-adrenal gland (HPA) axis

(White

et al., 1990, Cintra et al., 1991, Ponsalle et al., 1992 and Makimura et al.,

2003).

It has been reported that neonatal maternal separation, an animal model of a

stressful experience in childhood, can permanently modify HPA axis

characteristics

of the offspring (Plotsky and Meaney, 1993, Suchecki and Tufik, 1997, van Oers

et

al., 1998 and Liu et al., 2000). Experience of childhood abuse is prevalent

among

patients with eating disorders (Wonderlich et al., 1997; see for review), and

dysfunction of the HPA axis is implicated in the pathogenesis of eating

disorders

(Koo-Loeb et al., 2000, Putignano et al., 2001 and Gluck et al., 2004). It is

hypothesized that neonatal maternal separation may modulate the hypothalamic

expression of feeding peptides in offspring, perhaps in relation to altered HPA

axis

characteristics, and thus contribute to the pathogenesis of eating disorders.

Glucocorticoids are known to be involved in the regulation of energy balance

(Strack

et al., 1995), and some of the central effects of glucocorticoids are believed

to be

mediated by hypothalamic neuropeptides (Tempel and Leibowitz, 1994 and

Zakrzewska et

al., 1999). Food deprivation, a stressful episode, markedly elevates the plasma

level of corticosterone, representative glucocorticoid of rodents (Timofeeva et

al.,

2002, Makimura et al., 2003, Kim et al., 2004 and Jahng et al., 2005), and the

hypothalamic mRNA expression (Jahng et al., 1998, Swart et al., 2002 and Bi et

al.,

2003) and release (Kalra et al., 1991) of NPY. Regulation of the hypothalamic

NPY

expression by glucocorticoids has been suggested; adrenalectomy downregulates

the

expression of NPY gene in the hypothalamus (White et al., 1990); NPY neurons in

the

hypothalamic arcuate nucleus contain glucocorticoid receptors (Cintra et al.,

1991);

elevated plasma corticosterone appears to be necessary for fasting-induced

increase

of NPY mRNA expression (Ponsalle et al., 1992 and Makimura et al., 2003).

.... POMC neurons in the hypothalamus contain glucocorticoid receptors (Cintra

and

Bortolotti, 1992), and it was suggested that the hypothalamic expression of POMC

may

be mediated by glucocorticoids (Savontaus et al., 2002).

.... Sprague–Dawley rats ... pups ... males and ... females ... Rats were

sacrificed

on PND 60 [for examinations] ...

.... Table 1. Body weights (g) of the non-handled (NH) and the maternal

separation

(MS) groups

=================================

PND 22 29 36 43 50 57

=================================

NH 54.32±1.37 100.72±1.24 158.05±2.17 219.58±2.83 271.23±3.58 321.41±4.00

MS 59.80±0.81a 105.63±0.90a 163.50±1.97 223.98±3.37 275.70±2.90 325.97±3.38

=================================

a P < 0.001 vs. NH in each day, n = 30 per group, values are presented as

means±SE.

.... NPY mRNA levels in the arcuate nucleus of the free-fed MS (MS/FC) group did

not

differ from the free-fed NH (NH/FC) group (Fig. 2). Food deprivation

significantly

increased the arcuate NPY mRNA level in the NH group (P < 0.05; NH/FC vs.

NH/FD),

but not in the MS group (Fig. 2) [100 to 180 for the NH and 105 to 145 for the

MS

group]. POMC mRNA levels in the arcuate nucleus of MS/FC rats significantly

increased (P < 0.0001) compared to the NH/FC group (Fig. 3) [100 in NH and 135

in

FD.]. Food deprivation markedly reduced the arcuate POMC mRNA levels both in the

NH

(P < 0.05; NH/FC vs. NH/FD) and the MS (P < 0.01; MS/FC vs. MS/FD) groups (Fig.

3).

The deprivation effect on the arcuate POMC mRNA level appeared to be greater in

the

MS group (~43% reduction), compared to the NH group (~22% reduction).

.... The plasma level of corticosterone tended to be higher in the MS group

(MS/FC)

compared with the NH group (NH/FC), but not statistically significant (Fig.

4(a)).

Food deprivation significantly elevated the plasma corticosterone level in the

NH

group (P < 0.05; NH/FC vs. NH/FD), but not in the MS group (Fig. 4(a))

[increased

from 180 to 340 in NH and 220 to 285 in FC]. Basal levels of plasma leptin in

the MS

group did not differ from the NH group, and a major effect of food deprivation

was

found in both the NH (P < 0.0001; NH/FC vs. NH/FD) and the MS groups (P < 0.001;

MS/FC vs. MS/FD) (Fig. 4().

.... In summary, repeated maternal separation during the first 2 weeks of life

increased POMC mRNA levels in the hypothalamic arcuate nucleus of the rat

offspring

later in life. Body weight gain, basal levels of plasma corticosterone, leptin,

and

arcuate NPY mRNA were not modulated by experience of the neonatal maternal

separation. However, fasting-induced increases of plasma corticosterone and

hypothalamic NPY expression were blunted in MS rats. These results suggest that

neonatal maternal separation may increase the basal expression level of arcuate

POMC

mRNA, while inhibit the fasting-induced expression of arcuate NPY mRNA, later in

life. Lastly, the altered expression of arcuate NPY mRNA, but not of arcuate

POMC

mRNA, appeared to be related with altered activity of the HPA axis in offspring

by

neonatal maternal separation. ...

Al Pater, PhD; email: old542000@...

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