PMID- 15481801
OWN - NLM
STAT- MEDLINE
DCOM- 20041207
LR  - 20181101
IS  - 0391-4097 (Print)
IS  - 0391-4097 (Linking)
VI  - 27
IP  - 6 Suppl
DP  - 2004
TI  - Energy gradients for VT-signal migration in the CNS: studies on melanocortin 
      receptors, mitochondrial uncoupling proteins and food intake.
PG  - 23-34
AB  - The present paper enlightens a new point of view on brain homeostasis and 
      communication, namely how the brain takes advantage of different 
      chemical-physical phenomena such as pressure waves, and temperature and 
      concentration gradients to allow the homeostasis of the brain internal milieu as 
      well as some forms of intercellular communications (volume transmission, VT) at 
      an energy cost much lower than the classical synaptic transmission (the prototype 
      of wiring transmission, WT). The possible melanocortin control of uncoupling 
      protein 2 (UCP2) expression (hence of local brain temperature gradients) has been 
      studied in relation to food intake in male Wistar rats. Osmotic minipumps were 
      subcutaneously (sc) implanted in the midscapular region for 
      intracerebroventricular (icv) infusion. The control rats received an icv infusion 
      of 0.5 microl/h of artificial cerebrospinal fluid (ACSF), while experimental rats 
      received either an icv infusion of 0.16 nmol/h of HS024 or of 0.16 nmol/h of 
      adrenocorticotropin-(1-24) [ACTH-(1-24)]. The ACTH-treated group ate 
      significantly less than the ACSF-treated group during the first three days of 
      infusion, while, subsequently, food intake of the two groups was similar. On the 
      other hand, the HS024-treated group ate significantly more (up to 153% of the 
      control value) than ACSF- and ACTH-treated rats during the entire period. UCP2 
      mRNA analysis in arcuate nuclei of ACTH, HS024 and ACSF-treated animals showed a 
      significant 75% decrease (p<0.05 vs saline) of the total specific mRNA level in 
      the HS024-treated group vs ACSF-treated animals (control group), while no 
      significant change was observed between ACTH- and ACSF-treated animals. 
      Melanocortin antagonist HS024 via blockade of MCR4 increases food intake and via 
      a reduction of UCP2 expression enhances the food consumption ratio. This result 
      underlines the fact that UCP2 expression and food intake can be differentially 
      regulated. In other words, via a peptidergic control the central nervous system 
      (CNS) can modulate the energy stored from the amount of the food that the animal 
      has eaten and also uncouple the thermal micro-gradients (dependent on UCP2 
      expression) and hence the VT-signal micro-migrations from the food intake. It 
      should also be noticed that the control of the thermal gradients affects also the 
      neuronal firing rate and hence the transmitter release (likely above all the 
      release of peptides such as neuropeptide Y (NPY), melanin-concentrating hormone 
      (MCH) and beta-endorphin, e.g., in the arcuate nucleus representing signals 
      relevant to energy homeostasis). Thus, WT and VT are both modulated by 
      peptidergic signals that affect thermal gradients.
FAU - Agnati, L F
AU  - Agnati LF
AD  - Section of Physiology, Department of Medicine, University of Modena and Reggio 
      Emilia, Modena, Italy. luigiagnati@tin.it
FAU - Vergoni, A V
AU  - Vergoni AV
FAU - Leo, G
AU  - Leo G
FAU - Genedani, S
AU  - Genedani S
FAU - Franco, R
AU  - Franco R
FAU - Bertolini, A
AU  - Bertolini A
FAU - Fuxe, K
AU  - Fuxe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Neuropeptide Y)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Pituitary Hormone)
RN  - 0 (Ucp2 protein, rat)
RN  - 0 (Uncoupling Protein 2)
RN  - 60617-12-1 (beta-Endorphin)
RN  - 810S9KV11R (MSH receptor)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
SB  - IM
MH  - Adrenocorticotropic Hormone/metabolism
MH  - Animals
MH  - Body Temperature/physiology
MH  - Cell Communication/physiology
MH  - Central Nervous System/*physiology
MH  - Cerebral Cortex/physiology
MH  - Cerebrovascular Circulation/physiology
MH  - Eating/*physiology
MH  - Energy Metabolism/*physiology
MH  - Ion Channels
MH  - Male
MH  - Membrane Transport Proteins/*physiology
MH  - Mitochondria/drug effects/*metabolism
MH  - Mitochondrial Proteins/*physiology
MH  - Neuropeptide Y/physiology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Pituitary Hormone/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skull/physiology
MH  - Uncoupling Protein 2
MH  - beta-Endorphin/metabolism
EDAT- 2004/10/16 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/16 09:00
PHST- 2004/10/16 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/16 09:00 [entrez]
PST - ppublish
SO  - J Endocrinol Invest. 2004;27(6 Suppl):23-34.