An initial series of experiments with rats in a swimming pool established that they could find a hidden platform the location of which was defined in terms of 3 or 4 landmarks and that, when trained with all 4, any subset of 3 (or even, after a sufficient number of swimming trials, 2) landmarks was sufficient to produce accurate performance. When only one landmark was present during testing, however, performance fell to chance. Two additional experiments demonstrated a significant blocking effect: If rats were first trained to locate the platform with 3 landmarks, they did not learn to use a 4th landmark added to their initial set of 3.

No abstract

Glial cell line-derived neurotrophic factor (GDNF) was assayed for its neurotrophic effects against the neuronal atrophy that causes cognitive deficits in old age. Aged Fisher 344 rats with impairment in the Morris water maze received intrahippocampal injections at the dorsal CA1 area of either a lentiviral vector encoding human GDNF or the same vector encoding human green fluorescent protein as a control. Recombinant lentiviral vectors constructed with human cytomegalovirus promotor and pseudotyped with lyssavirus Mokola glycoprotein specifically transduced the astrocytes in vivo. Astrocyte-secreted GDNF enhanced neuron function as shown by local increases in synthesis of the neurotransmitters acetylcholine, dopamine and serotonin. This neurotrophic effect led to cognitive improvement of the rats as early as 2 weeks after gene transduction. Spatial learning and memory testing showed a significant gain in cognitive abilities due to GDNF exposure, whereas control-transduced rats kept their performance at the chance level. These results confirm the broad spectrum of the neurotrophic action of GDNF and open new gene therapy possibilities for reducing age-related neurodegeneration.

No abstract

No abstract