Molecular linking brain to mind

• Autorzy: Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

The Merriam-Webster Dictionary derives term “Mind” from Old English gemynd; akin to Old High German gimunt meaning memory. Over the last quarter of century we have followed molecular roots of the memory in a hope to identify also building blocks of the mind. Initially, we have identified increased c-fos mRNA levels in memory formation, thus discovering phenomenon of gene expression in learning. Following c-Fos protein function as transciptional regulator, we have focused on its gene targets: TIMP-1 and MMP-9 (tissue inhibitor of matrix metalloproteinases-1 and matrix metalloproteinase-9), composing extracellular proteolytic system that we and others have implicated as a major player in the synaptic plasticity, learning and memory. MMP-9 has been shown first to be activated in dendritic remodeling, accompanying epileptogenesis. Then, functional studies demonstrated MMP-9 role in learning and memory as well as their cellular models and finally epileptogenesis. At the subcellular level, MMP-9 localization and activity helps to explain this role, as the enzyme, its protein and mRNA are all available at the or near excitatory synapses located at the dendritic spines to allow for a rapid, local unleash of the enzymatic activity in response to synaptic stimulation. Furthermore, MMP-9 was shown to directly affect the dendritic spine morphology and excitatory neurotransmitter receptor function and trafficking. In aggregate, the pivotal role of MMP-9 in the synaptic plasticity underlying brain physiology has been firmly established. The present research challenge is to explain possible contribution of the enzyme to such human neuropsychiatric conditions as epilepsy, drug addiction, schizophrenia and autism spectrum disorders to name just those for which such a link has been demonstrated. By these virtues, MMP-9 emerges indeed as a molecular link to the brain molecular underpinning of the mind

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S11

Twórcy

autor

Kaczmarek L.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland