Expression of membrane-associated carbonic anhydrase XIV on neurons and axons in mouse and human brain

Although long suspected from histochemical evidence for carbonic anhydrase (CA) activity on neurons and observations that CA inhibitors enhance the ex tracellular alkaline shifts associated with synaptic transmission, an extra cellular CA in brain had not been identified. A candidate for this CA was s uggested by the recent discovery of membrane CA (CA XIV) whose mRNA is expr essed in mouse and human brain and in several other tissues. For immunoloca lization of CA XIV in mouse and human brain, we developed two antibodies, o ne against a secretory form of enzymatically active recombinant mouse CA XI V, and one against a synthetic peptide corresponding to the 24 C-terminal a mino acids in the human enzyme. Immunostaining for CA XIV was found on neur onal membranes and axons in both mouse and human brain. The highest express ion was seen on large neuronal bodies and axons in the anterolateral part o f pens and medulla oblongata. Other CA XIV-positive sites included the hipp ocampus, corpus callosum, cerebellar white matter and peduncles, pyramidal tract, and choroid plexus, Mouse brain also showed a positive reaction in t he molecular layer of the cerebral cortex and granular cellular layer of th e cerebellum. These observations make CA XIV a likely candidate far the ext racellular CA postulated to have an important role in modulating excitatory synaptic transmission in brain.