Trophic factors during normal brain aging and after functional damage

Abstract

There is an increasing body of information concerning the physiological role of several target-derived neurotrophic proteins that are structurally and functionally related to the classical neurotrophic molecule NGF and which resemble a genetic family called neurotrophins. However apart from NGF, there is little knowledge about the pathophysiological role of these neurotrophins concerning aging or dementia. To our present knowledge, decreased NGF production does not seem to play a causal role in age-related cognitive impairment which is usually associated with neurodegenerative processes in the cholinergic basal forebrain system. However, there are several experimentally found indications that NGF might be of importance in the stimulation of compensatory changes and repair mechanisms. Moreover, recent findings suggest that disturbances in cerebral glucose metabolism may play an important role in cognitive disabilities during normal aging and also in dementia disorders such as Alzheimer's disease. Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to decrease cerebral glucose utilization and energy metabolism and to impair passive avoidance learning in adult rats. One week after ICV STZ treatment, NGF content was significantly decreased in the septal region, where NGF-responsive cell bodies are known to be located and where NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels were increased within 3 weeks after ICV STZ treatment by about the same magnitude as has been observed for aged learning-impaired rats in the target regions for the basal forebrain cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)