title: Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.
abstract: Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Max-Planck-Institute for Psychiatry, Clinical Institute, Munich, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hellweg
authors.forename: R
authors.initials: R
authors.lastname: Nitsch
authors.forename: C
authors.initials: C
authors.lastname: Hock
authors.forename: M
authors.initials: M
authors.lastname: Jaksch
authors.forename: S
authors.initials: S
authors.lastname: Hoyer
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D009414:Nerve Growth Factors; D013311:Streptozocin; D002795:Choline O-Acetyltransferase; D005947:Glucose