PMID- 10213096
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20191210
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 407
IP  - 2
DP  - 1999 May 3
TI  - Cyclic AMP phosphodiesterases are localized in regions of the mouse brain
      associated with reinforcement, movement, and affect.
PG  - 287-301
AB  - Four cyclic AMP-specific, rolipram-inhibited phosphodiesterases (PDE4s) have been
      identified in mammals; all four are homologs of dunce, a gene required for
      learning and memory in Drosophila. To determine the distribution of PDE4s in the 
      mammalian brain, specific antibodies were generated against the proteins encoded 
      by each of three dunce homologs PDE4A, PDE4B, and PDE4D in the mouse. On Western 
      blots, these antibodies recognized multiple protein species in all brain regions 
      studied. Immunohistochemical studies showed that both cell bodies and neuropil
      were well labeled in selected regions throughout the brain. Immunoreactivity for 
      PDE4A was found predominantly in the anterior olfactory nucleus, subiculum, layer
      V pyramidal neurons from the cerebral cortex, and corticospinal tracts. By
      contrast, anti-PDE4B-labeled neurons were observed in the inferior olive, the
      paraventricular and supraoptic nuclei of the hypothalamus, and in the ventral
      striatum. Regions of neuropil containing high levels of PDE4B immunoreactivity
      included the cerebellar molecular layer, globus pallidus, nucleus accumbens, and 
      substantia nigra. Anti-PDE4D antibody distinctly labeled cerebellar Purkinje
      cells as well as neurons in the medial habenula and thalamic nuclei. Fibers in
      the fasciculus retroflexus, interpeduncular nuclei, and periaqueductal gray were 
      also stained with this antibody. These findings indicate that the distribution of
      PDE4s in the brain is remarkably segregated, and suggest that each of these
      enzymes has a unique functional role. Furthermore, the data support the notion
      that rolipram, the PDE4-specific inhibitor that acts as an antidepressant in
      humans, may mediate its behavioral effects through PDE4B, which is highly
      localized to neural pathways known to underlie reward and affect in mammals.
FAU - Cherry, J A
AU  - Cherry JA
AD  - Department of Psychology, Boston University, Massachusetts 02215, USA.
      jcherry@bu.edu
FAU - Davis, R L
AU  - Davis RL
LA  - eng
GR  - DC03019/DC/NIDCD NIH HHS/United States
GR  - GM47680/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Isoenzymes)
RN  - 0 (Pyrrolidinones)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - K676NL63N7 (Rolipram)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/*analysis/metabolism
MH  - Affect/*physiology
MH  - Animals
MH  - Brain/enzymology/*physiology
MH  - Drosophila
MH  - Female
MH  - Isoenzymes/analysis/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Motor Activity/*physiology
MH  - Neurons/enzymology
MH  - Organ Specificity
MH  - Pyrrolidinones/pharmacology
MH  - *Reinforcement, Psychology
MH  - Rolipram
EDAT- 1999/04/23 02:02
MHDA- 2000/06/20 09:00
CRDT- 1999/04/23 02:02
PHST- 1999/04/23 02:02 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/04/23 02:02 [entrez]
AID - 10.1002/(SICI)1096-9861(19990503)407:2<287::AID-CNE9>3.0.CO;2-R [pii]
PST - ppublish
SO  - J Comp Neurol. 1999 May 3;407(2):287-301.