Ramified parenchymal microglia may provide immune surveillance in the nervous system and become activated in response to injury, showing increases in antigens found on macrophages, e.g. CD4 and MHCs. We investigated in adult rats the effects of a 2-week intraventricular infusion with ciliary neurotrophic factor (CNTF), a nervous system-associated cytokine, on microglia of the normal and injured corpus callosum. CNTF caused morphological changes, induced the expression of low-affinity nerve growth factor receptor and CD4 and increased the expression of complement receptor 3. Such changes were also observed after treatment of pure cultures of neonatal rat microglial cells with highly purified CNTF, suggesting a direct responsiveness to CNTF. Thus, endogenous astroglial and Schwann cell-derived CNTF may be an important component of the immune responses of the nervous system.

Animals↗

PubMedDate not supplied

Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor.

In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal-diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF). In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death and promote behavioural recovery after damage to the septo-hippocampal connections. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.

Acetylcholinesterase↗

PubMedDate not supplied

Neuronotrophic and neurite-promoting factors and their clinical potentials.

Neuronal maintenance and neuritic growth during development are increasingly recognized as being under the extrinsic control of neuronotrophic- and neurite-promoting agents. Protein agents ('factors') are the most studied but not the only molecules exerting such controls. It appears increasingly likely that adult neurons in situ are equally subject to similar extrinsic regulations. Two recently studied in vivo models for peripheral and central neural regeneration have demonstrated trauma-related accumulations of neuronotrophic- and neurite-promoting factors in the adult rat, in close temporal correlation with neuronal maintenance and axonal regrowth, respectively. Deficits in the supply or utilization of similar factors may underlie neuronal or glial regressive processes in aging, and in selected neuronal diseases such as Parkinson, ALS and Alzheimer. Speculative approaches to, and potential problems of, clinical interventions addressing putative neuronotrophic deficits are discussed.

Aging↗