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NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.4, August 2002

ORIGINAL ARTICLE
Effect of functional pinealectomy on NMDAR

2002; 23:345350
pii: NEL230402A10
PMID: 12195239

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Effect of functional pinealectomy on hippocampal lipid peroxidation, antioxidant enzymes and N-methyl-D-aspartate receptor subunits 2A and 2B in young and old rats

Namik Delibas, Nalan Tuzmen, Zafer Yonden & Irfan Altuntas

Suleyman DemirelUniversity, School of Medicine, Department of Biochemistry and Clinical Biochemistry, Isparta, Turkey.

Key words:
melatonin; lipid peroxidation; antioxidant enzymes; NMDA receptors; rat

Submitted: July 29, 2002
Accepted: July 30, 2002

ABSTRACT

OBJECTIVES: To investigate the effects of pinealectomy on lipid peroxidation, antioxidant status and NMDA receptor subunits 2A and 2B concentrations in hippocampus.

DESIGN: Forty-eight male Wistar-albino rats were used.

SETTINGS: Animals were divided into three groups: 24 h dark throughout the study (highest melatonin release), 24 h light exposure (light-induced functional pinealectomy) and 12 h light/12 h dark exposure (control group). Thereafter, each group was divided into two groups as young and old animals.

RESULTS: There was an increase in NR2A and NR2B concentration in DY group compared to all other treatments. CuZn and Mn SOD activities were found to be increased in CO compared to CY group. Continual light exposure for 4 weeks did not change neural CuZn and Mn SOD activities. In old rats, light exposure reduced the activities of both CuZn and Mn SOD relative to those in the young animals. In addition, CuZn and Mn SOD activities were higher in dark exposed rats than in those in the continual light exposed or LD 12:12 rats. GSH-Px activity was found elevated in the DY rats compared to the CY groups. MDA levels were significantly higher in the CO than in the CY group.

CONCLUSIONS: NR2A and NR2B receptor concentrations in hippocampus of the rats maintained in dark showed significant increases compared to the control and functional pinealectomy groups but there was no significant increase in lipid peroxidation.

 

ABBREVIATIONS
ROS – Reactive oxygen species
NMDAR – N-methyl D-aspartat receptors
CNS – Central nervous system
NR2A – NMDA receptor subunit 2A
NR2B – NMDA receptor subunit 2B
Mn SOD – Mn superoxide dismutase
CuZn SOD – CuZn superoxide dismutase
MDA – Malondialdehyde
CAT – Catalase
GSH – Glutathione
GSH-Px – Glutathione peroxidase
NR1 – NMDA receptor subunit 1
NR2 – NMDA receptor subunit 2
BCIP/NBT – 5-bromo-4-chloro-3-indolyl phosphate/nitroblue tetrazolium
EGTA – Ethylene glycol-bis (b-aminoethyl ether)-
N,N,N',N'-tetraacetic acid
PVDF – Polyvinylidene difluoride
CY – Control young
CO – Control old
LY – Light young
LO – Light old
DY – Dark young
DO – Dark old
PBS – Phosphate buffered saline
EDTA – Ethylenediaminetetraacetic acid
SDS/PAGE – Sodium dodecyl sulfate/polyacrylamide gel electrophoresis
TBST – Tris-buffered saline with Tween 20
BSA – Bovine serum albumin
LTP – Long-term potentiation
O.– – Superoxide

Introduction

Of all the organs in the body, the central nervous system (CNS) takes more than its share of oxidative abuse. The major reasons for this are its high utilization of O2, its relatively poorly developed antioxidant network, and the fact that it contains large amounts of easily oxidizable fatty acids [1]. Antioxidant defense system becomes insufficient in advanced ages and results in various diseases and symptoms of aging [2]. Melatonin is a secretory product mainly synthesized by the pineal gland and secreted primarily at night, when blood levels reach levels 10 times higher than those present in the daytime [3]. Melatonin is a well-known antioxidant that protects DNA, lipids, and proteins from free radical damage. Melatonin not only scavenges free radicals such as superoxide radicals and hydroxyl radicals, but also activates some antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) [1,3,4]. Furthermore, melatonin has been reported to increase mRNA levels for SOD [5]. Since endogenous melatonin levels fall markedly in advanced ages, the loss of this antioxidant may contribute to the incidence or severity of some age-associated neurodegenerative diseases [6].
The N-methyl-D-aspartate (NMDA) receptor is a member of the group ionotropic glutamate receptors. The NMDA receptor is a heteromeric protein composed of two classes of subunits, NR1 and NR2. Four separate genes encode NR2 subunits, NR2A to NR2D. While NR2 subunits cannot form functional channels when expressed alone, they can alter NMDAR channel properties when complexed with NR1 subunits [7]. This receptor is involved in a wide variety of processes in the central nervous system (CNS) including synaptogenesis and synaptic plasticity. Additionally, the NMDA receptor has been implicated in excitotoxicity, neurodegenerative disorders and aging [8–11]. Thus, a greater understanding of the modulation of this receptor is likely to be important to the understanding of the physiology and pathophysiology of these processes.
Though there are many reports regarding the effect of melatonin on lipid peroxidation and antioxidant enzymes [1,3–5], the effects of continuous light (low melatonin) and dark (high melatonin) on NMDA receptor concentration in the hippocampus is lacking. Also, it is not known how NMDA receptor concentrations in hippocampi of young and old animals change in response to light and dark. Hence, we have undertaken this study to investigate lipid peroxidation, antioxidant status and NMDA receptor subunits 2A and 2B concentrations in hippocampus of young and old rats exposed to 24h light (functional pinealectomy), 24 h dark and 12h light/12h dark for 4 weeks.

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