title: Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats.
abstract: Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-α-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Lima
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: V M
authors.initials: VM
authors.lastname: Sardinha
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Oliveira
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Reis
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Mota
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Silva
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Marques
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cerqueira
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Pinto
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Sousa
authors.affiliation: 1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: J F
authors.identifier: 0000000210052328
authors.initials: JF
authors.lastname: Oliveira
mesh_terms: D015074:2-Aminoadipic Acid / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D001284:Atrophy; D001288:Attention / Q000187:drug effects; D016923:Cell Death; D003071:Cognition / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008845:Microinjections; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D012193:Reversal Learning / Q000187:drug effects
chemical_list: D015074:2-Aminoadipic Acid