Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.

Objective: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety, and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and complex 2 (mTORC2) activities in the brain, given that both pathways may represent unique targets for treatment.

Methods: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes.

Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons.

Nectins are cell adhesion molecules that, together with the intracellular binding partner afadin, mediate adhesion and signaling at a variety of intercellular junctions. In this work we studied the distribution of nectin-1 and afadin during hippocampal synapse formation using cultured primary hippocampal neurons. Nectin-1 and afadin cluster at developing synapses between hippocampal neurons.

Proteolytic processing of proNGF is necessary for mature NGF regulated secretion from neurons.

Nerve growth factor mediates neuronal survival, synaptogenesis, and synaptic remodeling. We utilized primary hippocampal cultures to investigate the intrinsic motifs of proNGF that might contribute to its processing and subsequent allocation to a regulated versus constitutive secretory pathway. The addition of a carboxypeptidase E motif to proNGF did not alter the secretion of NGF.

Neurotrophin secretory pathways and synaptic plasticity.

Neurotrophins and synaptic activity work in conjunction during the process of synaptic plasticity. Both are required to stabilize new synaptic structures and the loss of either can lead to cognitive impairments, as new information cannot be stored efficiently or later recalled. Neurotrophins are becoming recognized as mediators of activity-dependent plasticity.