Neurofibrillary tangle-related synaptic alterations of spinal motor neurons of P301L tau transgenic mice.

We investigated axosomatic synapses of anterior horn cells of transgenic (TG) mice expressing mutant P301L human tau and non-transgenic (NTG) mice using electron microscopic methods to demonstrate the relationship between neurofibrillary tangles (NFTs) and synaptic alterations. Animals aged 3.5-8.5 months were used because at this age many motor neurons in TG mice have NFTs. We measured the perimeter of anterior horn cell perikarya, the number of boutons and total length of boutons in contact with the neuronal perikarya from the micrographs of NFT and non-NFT-bearing neurons. We also calculated the proportion of the perimeter covered by boutons, density of boutons and mean size of boutons. The density of synaptic boutons in contact with NFT-bearing neurons was significantly decreased compared to non-NFT-bearing neurons. These findings suggest that synaptic reduction occurs during neurofibrillary degeneration and is probably associated with NFT. In addition, synaptic boutons were detached from NFT-bearing neurons with the resulting space occupied by astrocytic processes, suggesting that astrocytes may be involved in the observed synaptic alterations.