GABA(A) Receptors Are Well Preserved in the Hippocampus of Aged Mice

GABA is the primary inhibitory neurotransmitter in the nervous system. GABA(A) receptors (GABA(A)Rs) are pentameric ionotropic channels. Subunit composition of the receptors is associated with the affinity of GABA binding and its downstream inhibitory actions. Fluctuations in subunit expression levels with increasing age have been demonstrated in animal and human studies. However, our knowledge regarding the age-related hippocampal GABA(A)R expression changes is limited and based on rat studies. This study is the first analysis of the aging-related changes of the GABA(A)R subunit expression in the CA1, CA2 3, and dentate gyrus regions of the mouse hippocampus. Using Western blotting and immunohistochemistry we found that the GABAergic system is robust, with no significant age-related differences in GABA(A)R alpha1, alpha2, alpha3, alpha5, beta3, and gamma2 subunit expression level differences found between the young (6 months) and old (21 months) age groups in any of the hippocampal regions examined. However, we detected a localized decrease of alpha2 subunit expression around the soma, proximal dendrites, and in the axon initial segment of pyramidal cells in the CA1 and CA3 regions that is accompanied by a pronounced upregulation of the alpha2 subunit immunoreactivity in the neuropil of aged mice. In summary, GABA(A)Rs are well preserved in the mouse hippocampus during normal aging although GABA(A)Rs in the hippocampus are severely affected in age-related neurological disorders, including Alzheimers disease.GABA is the primary inhibitory neurotransmitter in the nervous system. GABA(A) receptors (GABA(A)Rs) are pentameric ionotropic channels. Subunit composition of the receptors is associated with the affinity of GABA binding and its downstream inhibitory actions. Fluctuations in subunit expression levels with increasing age have been demonstrated in animal and human studies. However, our knowledge regarding the age-related hippocampal GABA(A)R expression changes is limited and based on rat studies. This study is the first analysis of the aging-related changes of the GABA(A)R subunit expression in the CA1, CA2 3, and dentate gyrus regions of the mouse hippocampus. Using Western blotting and immunohistochemistry we found that the GABAergic system is robust, with no significant age-related differences in GABA(A)R alpha1, alpha2, alpha3, alpha5, beta3, and gamma2 subunit expression level differences found between the young (6 months) and old (21 months) age groups in any of the hippocampal regions examined. However, we detected a localized decrease of alpha2 subunit expression around the soma, proximal dendrites, and in the axon initial segment of pyramidal cells in the CA1 and CA3 regions that is accompanied by a pronounced upregulation of the alpha2 subunit immunoreactivity in the neuropil of aged mice. In summary, GABA(A)Rs are well preserved in the mouse hippocampus during normal aging although GABA(A)Rs in the hippocampus are severely affected in age-related neurological disorders, including Alzheimers disease.