Excess glucocorticoid exposure affects emotional and cognitive brain functions. The extreme form, Cushing’s Syndrome, is adequately modeled in the AdKO_2.0 mouse, consequential to adrenocortical hypertrophy and hypercorticosteronemia. We previously reported that the AdKO2.0 mouse brain undergoes volumetric changes that resemble closely those of Cushing’s Syndrome human patients, as well as changes in expression of glial related marker proteins. In the present work, the expression of genes related to glial and neuronal cell populations and functions was assessed in multiple forebrain areas and hypothalamus. Glucocorticoid target genes were consistently regulated, including CRH mRNA suppression in the hypothalamus and induction in amygdala and hippocampus. Glial genes expression was consistently affected in the AdKO2.0 mouse brain, pointing to different activation status rather than cell numbers. Generic markers for neuronal cell populations, and cellular integrity were only slightly affected. The findings highlight the vulnerability of glial cell populations to chronic high levels of circulating glucocorticoids.