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Schizophrenia and Decreasing in Corticolimbic Gabaergic Function
*Corresponding author: Behzad Saberi, Medical Research, Esfahan, Iran
Received: May 15, 2019; Published: June 19, 2019
Glutamic Acid Decarboxylase (GAD) and Gamma Amino Butyric Acid (GABA) activities in the cortex, nucleus accumbens and thalamus would be decreased in schizophrenia. Also, there would be a reduction in presynaptic markers in some GABAergic interneurons in hippocampus and frontal cortex. Glutamic acid decarboxylase 65 KDa is expressed in axons and terminals while Glutamic acid decarboxylase 67 is expressed in dendrites and perikarya. Neurons which express GAD 67 mRNA in prefrontal cortex and other brain parts are reduced in numbers than ones expressing GAD 65 .
Calcium binding proteins like Parvalbumin (PV), Calbindin and Calretin expressions are done by GABAergic interneurons and modulated by afferent synaptic activity. Calbindin is found in double bouquet cells while calretin is found in bipolar neurons and double bouquet cells. PV is found in basket and chandelier cells in the cortex and pyramidal neurons send input to that also. Cartridges and pyramidal cells are the centre for their synaptic contacts and pyramidal cell firing is influenced by them, results in cortical excitatory output coordination. PV expression reduction is found in the prefrontal cortex of the patients with schizophrenia . The amount of neurons with PV mRNA in prefrontal cortex in schizophrenia is intact while the amount of mRNA per neuron is decreased . Calretin mRNA expression would not be altered in schizophrenia while mRNA encoding for GABA-A receptors, GAT1, GABA membrane transporters, GAD 67, Somatostatin and PV is decreased in primary visual and motor, anterior cingulate and primary motor cortex. GAT1 expression reduction in hippocampus and prefrontal cortex is seen in schizophrenia. Also, cartridges of GABAergic terminal boutons density reduction are seen in schizophrenia [4,5].
GAT1 and GAD67 reductions would cause different results, GAT1 reduction causes GABAergic neurotransmission enhancement while GAD67 reduction causes GABAergic neurotransmission reduction [6,7]. Increasing in GABA-A receptors can be found in intermediate layers of the cortex located in pyramidal neurons. GABA-A receptor subunits including Alpha 5 and Alpha 1 are increased in prefrontal cortex [8,9].
The overall results of these findings suggest that corticolimbic GABAergic function would be decreased in .
- Volk DW, Pierri JN, Fritschy JM, Auh S, Sampson AR, et al. (2002) Reciprocal alterations in pre - and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia. Cereb Cortex 12 (10): 1063–1070.
- Woo TU, Whitehead RE, Melchitzky DS, Lewis DA (1998) A subclass of prefrontal gamma - aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci U S A 95(9): 5341-5346.
- Reynolds GP, Czudek C, Andrews HB (1990) Defi cit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. Biol Psychiatry 27(9): 1038-1044.
- Conde F, Lund JS, Jacobowitz DM, Baimbridge KG, Lewis DA (1994) Local circuit neurons immunoreactive for calretinin, calbindin D - 28k or parvalbumin in monkey prefrontal cortex: distribution and morphology. J Comp Neurol 341(1): 95-116.
- Beasley CL, Reynolds GP (1997) Parvalbumin - immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res 24(3): 349-355.
- Volk D, Austin M, Pierri J, Sampson A, Lewis D (2001) GABA transporter - 1mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons. Am J Psychiatry 158(2): 256-265.
- Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 52(4): 258-266.
- Heckers S, Stone D, Walsh J, Shick J, Koul P, et al. (2002) Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry 59(6): 521-529.
- Akbarian S, Huang HS (2006) Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. Brain Res Rev 52(2): 293-304.
- Kaufman DL, Houser CR, Tobin AJ (1991) Two forms of the gammaaminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem 56(2): 720-723.