Ok, some more.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Aug;22(4):121-9. Related
Articles, Links
[Modifications of several pharmacological actions by diabetes:
effects on the opioid receptor agonist and benzodiazepines]
[Article in Japanese]
Kamei J, Zushida K, Miyata S.
Department of Pathophysiology and Therapeutics, Hoshi University
School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara,
Shinagawa-ku, Tokyo, 142-8501 Japan.
Diabetic neuropathy is a most-convoluted complication. Diabetic
gastropathy, ulcers, diarrhea, and bladder dysfunction are the major
peripheral neuropathies. Peripheral neuropathies have been the primary
neuroscience focus of diabetes research. In contrast to the periphery,
the brain is not usually thought to be a target of chronic diabetic
complications. However, the impact of diabetes mellitus on the central
nervous system has recently gained attention. It is well known that
diabetes or hyperglycemia influences the sensitivity of laboratory
animals to various pharmacological agents. An increased sensitivity of
hyperglycemic or diabetic animals to barbiturates and a decreased
sensitivity of D-amphetamine, p-chloroamphetamine, and carbon
tetrachloride have been demonstrated. Furthermore, it was reported that
mice and rats with streptozotocin-induced diabetes and spontaneously
diabetic mice are significantly less sensitive than non-diabetic mice to
the antinociceptive effect of morphine. However, little information is
available regarding the mechanism responsible for these changes. It is
well established that anxiety and depression are common in patients with
diabetes. Moreover, diabetic animals showed significantly more
anxiogenic activity than non-diabetic animals did. However, the
mechanisms through which diabetes may contribute to the development of,
or be a risk factor for, psychiatric disorders are not clear. We provide
an overview of our current understanding of the effects of
streptozotocin-induced diabetes on the opioid receptor and the
benzodiazepine receptor.
Publication Types:
* Review
* Review, Tutorial
PMID: 12373865 [PubMed - indexed for MEDLINE]
J Pharmacol Exp Ther. 2002 Jun;301(3):1067-78. Related Articles, Links
Click here to read
SSR180575
(7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]
indole-1-acetamide), a peripheral benzodiazepine receptor ligand,
promotes neuronal survival and repair.
Ferzaz B, Brault E, Bourliaud G, Robert JP, Poughon G, Claustre Y,
Marguet F, Liere P, Schumacher M, Nowicki JP, Fournier J, Marabout B,
Sevrin M, George P, Soubrie P, Benavides J, Scatton B.
Discovery Research, Central Nervous System Research Department,
Sanofi-Synthelabo Recherche, 31 avenue P. Vaillant-Couturier, 92225
Bagneux Cedex, France.
In the present study, we have investigated the potential
neuroprotective effects of a novel peripheral benzodiazepine binding
site (PBR) ligand,
7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]i
ndole-1-acetamide (SSR180575), in models of central and peripheral
neurodegeneration in vivo and its effect on steroid concentrations in
plasma and nervous tissue. SSR180575 shows high affinity (IC(50),
2.5-3.5 nM) and selectivity for the rat and human PBR and potently
inhibits the in vivo binding of [(3)H]alpidem to PBR in the rat brain
and spleen after oral or i.p. administration (ID(50), 0.1-0.3 mg/kg). In
an experimental model of motoneuron degeneration induced by facial nerve
axotomy in the immature rat, SSR180575 given i.p. or orally for 8 days
rescued facial motoneurons, increasing their survival by 40 to 72% at 6
and 10 mg/kg p.o. b.i.d. Moreover, in this model, SSR180575 (10 mg/kg
p.o. b.i.d.) increased by 87% the number of motoneurons immunoreactive
to peripherin, a type III intermediate filament, whose expression is
up-regulated during nerve regeneration. SSR180575 also improved
functional recovery in acrylamide-induced neuropathy in the rat when
given therapeutically at 2.5 to 10 mg/kg/day p.o. Furthermore, SSR180575
(3 mg/kg i.p. b.i.d.) accelerated functional recovery of the blink
reflex after local injury of the facial nerve in the rat. SSR180575
increased pregnenolone accumulation in the brain and sciatic nerve
(+100% at 3 mg/kg i.p.), suggesting that its neuroprotective effects are
steroid-mediated. These results indicate that PBR ligands (e.g.,
SSR180575) promote neuronal survival and repair in axotomy and
neuropathy models and have potential for the treatment of
neurodegenerative diseases (e.g., peripheral neuropathies or amyotrophic
lateral sclerosis).
PMID: 12023539 [PubMed - indexed for MEDLINE]
Brain Res Brain Res Rev. 2001 Nov;37(1-3):360-71. Related Articles,
Links
Click here to read
Neuroactive steroids and peripheral myelin proteins.
Magnaghi V, Cavarretta I, Galbiati M, Martini L, Melcangi RC.
Department of Endocrinology and Center of Excellence for
Neurodegenerative Disorders, University of Milan, Via Balzaretti 9,
20133, Milan, Italy.
The present review summarizes observations obtained in our
laboratories which underline the importance of neuroactive steroids
(i.e., progesterone (PROG), dihydroprogesterone (5alpha-DH PROG),
tetrahydroprogesterone (3alpha, 5alpha-TH PROG), testosterone (T),
dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol
(3alpha-diol)) in the control of the gene expression of myelin proteins
(i.e. glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22))
in the peripheral nervous system. Utilizing different in vivo (aged and
adult male rats) and in vitro (Schwann cell cultures) experimental
models, we have observed that neuroactive steroids are able to stimulate
the mRNA levels of Po and PMP22. The effects of these neuroactive
steroids, which are able to interact with classical (progesterone
receptor, PR, and androgen receptor, AR) and non-classical (GABA(A)
receptor) steroid receptors is further supported by our demonstration in
sciatic nerve and/or Schwann cells of the presence of these receptors.
On the basis of the observations obtained in the Schwann cells cultures,
we suggest that the stimulatory effect of neuroactive steroids on Po is
acting through PR, while that on PMP22 needs the GABA(A) receptor. The
present findings might be of importance for the utilization of specific
receptor ligands as new therapeutical approaches for the rebuilding of
the peripheral myelin, particularly in those situations in which the
synthesis of Po and PMP22 is altered (i.e. demyelinating diseases like
Charcot-Marie-Tooth type 1A and type 1B, hereditary neuropathy with
liability to pressure palsies and the Dejerine-Sottas syndrome, aging,
and after peripheral injury).
Publication Types:
* Review
* Review, Tutorial
PMID: 11744100 [PubMed - indexed for MEDLINE]
