A quantitative ultrastructural study of the effects of phenylacetate on synaptic organization in the developing rat cerebral cortex.

Male rats were injected with either phenylacetate (PA; a phenylalanine metabolite) or saline (control). Osmicated tissue from the parietal cortex was analyzed qualitatively and quantitatively, attention being focused on possible synaptic changes in the molecular layer. PA-treated rats differed from controls in the following ways: a 20% decrease in body weight at 21 days, and a reduction in brain weight at 10 and 21 days; the presence of 'atypical' profiles (possibly derived from axonal growth cones) in the neuropil; a lag in the accretion of synapses per 100 micron2 of tissue, and of vesicles per micron2 of presynaptic terminal; the presence of a 'crossover' in the developmental trend for several synaptic organizational parameters between days 15 and 21; an elevation in synaptic density at day 21; an increased proportion of negatively curved synapses at 21 days; a significant difference in the preponderance of axodendritic synapses over days 7-21. This suggests that the metabolism of some neurons in the PA brain is initially different from normal, with a lag in synaptic development being evident. The increase in synaptic density and the relative preponderance of other synaptic parameters at 21 days signifies that an initial lag in development may alter the developmental scheme. This may be coupled with changes in synaptic efficacy and connectivity.