Free and conjugated GABA in human cerebrospinal fluid: effect of degenerative neurologic diseases and isoniazid.
gamma-Aminobutyric acid (GABA) was measured in CSF as such and following acid hydrolysis by the ion-exchange/fluorometric method. The conjugated GABA level was obtained by subtracting the free GABA level from the total GABA level. Results showed that at room temperature, while the free GABA level increased, the level of conjugated GABA decreased in a linear fashion during the first 24 h (r = -0.974; P less than 0.001). Aging and CSF conjugated GABA levels were inversely correlated (r = -0.613; P less than 0.05). Unlike free GABA levels, the levels of conjugated GABA were not altered in Huntington's disease, Parkinson's disease, cerebellar ataxias, dementias, epilepsy and multiple sclerosis compared to controls. In patients with Huntington's disease, on administration of isoniazid at 900 mg/day, along with pyridoxine at 100 mg/day, a 4-fold increase of both free (P less than 0.005) and conjugated GABA (P less than 0.0025) was seen. The results indicate that while total GABAergic peptides are not altered in several of the neurologic diseases studied, drugs such as isoniazid and/or pyridoxine can significantly elevate both free and conjugated GABA levels in human CSF.