Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons.
Increased neuroinflammatory reaction is frequently observed during normal brain aging. However, a direct link between neuroinflammation and neurodegeneration during aging has not yet been clearly shown. Here, we have characterized the age-related hippocampal inflammatory processes and the potential relation with hippocampal neurodegeneration. The mRNA expression of the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha), and the iNOs enzyme was significantly increased in aged hippocampus. Accordingly, numerous activated microglial cells were observed in aged rats. These cells were differentially distributed along the hippocampus, being more frequently located in the hilus and the CA3 area. The mRNA expression of somatostatin, a neuropeptide expressed by some GABAergic interneurons, and the number of somatostatin-immunopositive cells decreased in aged rats. However, the number of hippocampal parvalbumin-containing GABAergic interneurons was preserved. Interestingly, in aged rats, the mRNA expression of somatostatin and IL-1beta was inversely correlated and, the decrease in the number of somatostatin-immunopositive cells was higher in the hilus of dentate gyrus than in the CA1 region. Finally, intraperitoneal chronic lipopolysaccharide (LPS) injection in young animals mimicked the age-related hippocampal inflammation as well as the decrease of somatostatin mRNA expression. Present results strongly support the neuroinflammation as a potential factor involved in the age-related degeneration of somatostatin GABAergic cells.
Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
M Paz
MP
Gavilán
Elisa
E
Revilla
Cristina
C
Pintado
Angélica
A
Castaño
M Luisa
ML
Vizuete
Inés
I
Moreno-González
David
D
Baglietto-Vargas
Raquel
R
Sánchez-Varo
Javier
J
Vitorica
Antonia
A
Gutiérrez
Diego
D
Ruano
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010320:Parvalbumins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D052247:Nitric Oxide Synthase Type II