TY - JOUR
T1 - Post-natal Deletion of Neuronal cAMP Responsive-Element Binding (CREB)-1 Promotes Pro-inflammatory Changes in the Mouse Hippocampus
AU - Marchese, Elisa
AU - Di Maria, Valentina
AU - Samengo, Daniela Maria
AU - Pani, Giovambattista
AU - Michetti, Fabrizio
AU - Geloso, Maria Concetta
PY - 2017
Y1 - 2017
N2 - By taking advantage of a "floxed" conditional CREB mutant mouse (CREB1loxP/loxP), in which postnatal deletion of the Creb gene in the forebrain is driven by the calcium/calmodulin-dependent protein kinase II-α gene (Camk2a) promoter (BCKO mice), we here show that selective disruption of CREB function in adult forebrain neurons results, in adult mice, in morphological alterations at the hippocampal level, including hippocampal shrinkage, reduced somal volume of neurons, microgliosis and mild reactive astrocytosis, mainly involving the CA1 subfield. The huge increase of microglial cells showing a mild activated profile, and the higher percentage of double-stained GFAP/S100B astrocytes, together with the increased expression of S100b mRNA at hippocampal level, suggest the establishment of a sub-inflammatory environment in the hippocampus of BCKO mice compared with age-matched controls. Collectively, the present data link neuron-specific, adult deletion of CREB to hippocampal structural alterations and to the early appearance of neuropathological features closely resembling those occurring in the aged brain. This information may be valuable for the understanding of the role of CREB in neuroinflammatory pathways.
AB - By taking advantage of a "floxed" conditional CREB mutant mouse (CREB1loxP/loxP), in which postnatal deletion of the Creb gene in the forebrain is driven by the calcium/calmodulin-dependent protein kinase II-α gene (Camk2a) promoter (BCKO mice), we here show that selective disruption of CREB function in adult forebrain neurons results, in adult mice, in morphological alterations at the hippocampal level, including hippocampal shrinkage, reduced somal volume of neurons, microgliosis and mild reactive astrocytosis, mainly involving the CA1 subfield. The huge increase of microglial cells showing a mild activated profile, and the higher percentage of double-stained GFAP/S100B astrocytes, together with the increased expression of S100b mRNA at hippocampal level, suggest the establishment of a sub-inflammatory environment in the hippocampus of BCKO mice compared with age-matched controls. Collectively, the present data link neuron-specific, adult deletion of CREB to hippocampal structural alterations and to the early appearance of neuropathological features closely resembling those occurring in the aged brain. This information may be valuable for the understanding of the role of CREB in neuroinflammatory pathways.
KW - Astroglia
KW - Hippocampus
KW - Microglia
KW - Neuroinflammation
KW - S100B
KW - cAMP responsive-element binding (CREB)
KW - Astroglia
KW - Hippocampus
KW - Microglia
KW - Neuroinflammation
KW - S100B
KW - cAMP responsive-element binding (CREB)
UR - http://hdl.handle.net/10807/100485
U2 - 10.1007/s11064-017-2233-9
DO - 10.1007/s11064-017-2233-9
M3 - Article
SN - 0364-3190
VL - 42
SP - 2230
EP - 2245
JO - Neurochemical Research
JF - Neurochemical Research
ER -