Beta-adrenergic receptors regulate astrogliosis and cell proliferation in the central nervous system in vivo.
Astrocytes express several cell surface receptors including the beta 2 -adrenergic receptor. To explore whether beta-adrenergic receptors (beta-ARs) directly regulate astrogliosis and glial scar formation, we evaluated the effects of beta-AR activation and blockade on astrocyte hypertrophy and cell proliferation in rabbit optic nerves in vivo. Artificial cerebrospinal fluid (CSF), isoproterenol (ISO; a beta-agonist), or propranolol (PROP; a beta-antagonist) were infused via osmotic minipumps into non-injured and crushed optic nerves for 14 days. Changes in nerve cell numbers and astroglial hypertrophy were monitored by ethidium bromide nuclear staining and glial fibrillary acidic protein (GFAP) immunohistochemistry, respectively. In non-injured nerves infused with CSF or PROP, there were no alterations in GFAP-immunoreactivity or cell numbers compared to normal optic nerves; however, in non-injured nerves infused with ISO, there was a significant increase in both GFAP-immunoreactivity and cell number. In crushed optic nerves, there was a significant increase in both GFAP-immunoreactivity and cell number compared to normal nerves, and this increase was not altered by infusion of either CSF or ISO. In contrast, PROP infusion significantly reduced the crush-induced increase in GFAP-immunofluorescence and cell number. These findings suggest that a) beta-AR activation, in the absence of injury, can promote astroglial hypertrophy and cell proliferation; b) after injury, beta-AR activation drives injury-induced astrogliosis and cell proliferation; c) astrocyte beta-ARs are maximally stimulated after neuronal injury; and d) neuronal regeneration may be influenced, both positively and negatively, through the pharmacological manipulation of glial receptors.
Hodges-Savola
C
C
Department of Psychiatry, University of Minnesota, Minneapolis 55455, USA.
Rogers
S D
SD
Ghilardi
J R
JR
Timm
D R
DR
Mantyh
P W
PW
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001345:Autoradiography; D002455:Cell Division / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta