Expression of Calbindin, a Marker of Gamma-Aminobutyric Acid Neurons, Is Reduced in the Amygdala of Oestrogen Receptor β-Deficient Female Mice

Oestrogen receptor beta (ER beta) knock-out female mice display increased anxiety and decreased threshold for synaptic plasticity induction in the basolateral amygdala. This may suggest that the gamma-aminobutyric acid (GABA) inhibitory system is altered. Therefore, the immunoreactivity of main GABAergic markers-i.e., calbindin, parvalbumin, calretinin, somatostatin, alpha 1 subunit-containing GABAA receptor and vesicular GABA transporter-were compared in the six subregions (LA, BL, BM, ME, CE and CO) of the amygdala of adult female wild-type and ER beta knock-out mice using immunohistochemistry and quantitative methods. The influence of ER beta knock-out on neuronal loss and glia was also elucidated using pan-neuronal and astrocyte markers. The results show severe neuronal deficits in all main amygdala regions in ER beta knock-out mice accompanied by astroglia overexpression only in the medial, basomedial and cortical nuclei and a decrease in calbindin-expressing neurons (CB+) in the amygdala in ER beta knock-out mice compared with controls, while other markers of the GABAergic system remain unchanged. Concluding, the lack of ER beta led to failure in the structural integrity of the CB+ subpopulation, reducing interneuron firing and resulting in a disinhibitory effect over pyramidal function. This fear-promoting excitatory/inhibitory alteration may lead to the increased anxiety observed in these mice. The impact of neuronal deficits and astroglia overexpression on the amygdala functions remains unknown.