Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.
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)
Hellweg
R
R
Max-Planck-Institute for Psychiatry, Clinical Institute, Munich, Federal Republic of Germany.
Nitsch
R
R
Hock
C
C
Jaksch
M
M
Hoyer
S
S
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
D009414:Nerve Growth Factors; D013311:Streptozocin; D002795:Choline O-Acetyltransferase; D005947:Glucose