title: Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.
abstract: Traumatic brain injury (TBI) is one of the leading causes of death and disability in humans. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. Using an animal model of TBI we examined the effect of dietary restriction (DR) on the neuroapoptosis and Bcl-2 family genes as the main regulators of the intrinsic apoptotic pathway. Bcl-2, Bcl-xl and Bax mRNA and protein expression in the ipsilateral cortex of adult Wistar rats exposed to DR before TBI were studied from 2 to 28 days post injury. Our results showed that DR suppressed neuroapoptosis and promoted significant upregulation of antiapoptotic Bcl-2 and Bcl-xl mRNAs in the ipsilateral cortex following injury. Expression of the proapoptotic Bax gene increased in ad libitum (AL) fed rats but remained unchanged in rats exposed to DR. Although the expression of Bcl-2, Bcl-xl and Bax proteins was changed in a similar manner in both experimental groups, DR promoted a continuous increase in the Bcl-2:Bax protein ratio throughout the recovery period. Together with our previous finding that DR mediates inhibition of the extrinsic apoptotic pathway the present work reveals that modulation of the intrinsic pathway contributes to the beneficial effect of DR in brain injury. These findings provide new insight into the effects of DR on pro-survival signaling after injury, lending further support to its neuroprotective effect.
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Lončarević-Vasiljković
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Desanka
authors.initials: D
authors.lastname: Milanović
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Pešić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Tešić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Marjana
authors.initials: M
authors.lastname: Brkić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Divna
authors.initials: D
authors.lastname: Lazić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Avramović
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: selkan@ibiss.bg.ac.rs.
authors.forename: Selma
authors.initials: S
authors.lastname: Kanazir
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D031204:Caloric Restriction / Q000639:trends*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*; D051020:bcl-X Protein / Q000096:biosynthesis*
chemical_list: C000617196:Bcl2 protein, rat; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
keywords: Cortical stab injury; Dietary restriction; Intrinsic apoptotic pathway; Neuroapoptosis